Library

Landmark Trials

A curated reference of foundational trials in medicine — selected for clinical impact and teaching value.

Heart Failure

41 trials

A-HeFT

Hydralazine/isosorbide dinitrate in self-identified Black patients with HFrEF — reduced mortality, stopped early.

2004

AIRE

Ramipril in post-MI patients with HF — reduced all-cause mortality vs placebo.

1993

ATTR-ACT

Tafamidis in ATTR cardiomyopathy — reduced all-cause mortality and CV hospitalization vs placebo.

2018

CARE-HF

CRT-P vs medical therapy in HFrEF with wide QRS — reduced mortality and HF hospitalization.

2005

CHAMPION

Implantable hemodynamic monitor (CardioMEMS) in NYHA III HF — reduced HF hospitalizations.

2011

CHARM-Added

Candesartan added to ACE inhibitor in HFrEF — modestly reduced CV death and HF hospitalization.

2003

CHARM-Alternative

Candesartan in ACE inhibitor-intolerant HFrEF — reduced CV death/HF hospitalization vs placebo.

2003

CIBIS-II

Bisoprolol vs placebo in moderate-severe HFrEF — reduced all-cause mortality, stopped early for benefit.

1999

COMPANION

CRT-P and CRT-D vs medical therapy in advanced HF with wide QRS — reduced hospitalization/death.

2004

CONSENSUS

Enalapril vs placebo in NYHA IV HF — first trial to show ACE inhibitor mortality benefit, stopped early.

1987

COPERNICUS

Carvedilol in severe HFrEF — reduced all-cause mortality, expanded beta-blocker use to severe HF.

2001

DANISH

Prophylactic ICD in non-ischemic systolic HF — no significant all-cause mortality reduction.

2016

DAPA-HF

Dapagliflozin (SGLT2i) added to GDMT in HFrEF — first SGLT2i to show benefit regardless of diabetes status.

2019

DELIVER

Dapagliflozin in HFpEF (LVEF >40%) — extended SGLT2i benefit across the EF spectrum.

2022

EMPEROR-Preserved

Empagliflozin in HFpEF — first SGLT2i shown to reduce HF hospitalization regardless of ejection fraction.

2021

EMPEROR-Reduced

Empagliflozin in HFrEF — confirmed SGLT2i class benefit, reduced HF hospitalization and CV death.

2020

EMPHASIS-HF

Eplerenone in mild HFrEF (NYHA II) — extended MRA benefit to less severe heart failure.

2011

EPHESUS

Eplerenone in post-MI patients with LV dysfunction and HF — reduced all-cause mortality and CV events.

2003

EXPLORER-HCM

Mavacamten vs placebo in symptomatic obstructive HCM — improved exercise capacity and LVOT gradient.

2020

FINEARTS-HF

Finerenone (non-steroidal MRA) in HFmrEF/HFpEF — reduced CV death and HF events.

2024

GALACTIC-HF

Omecamtiv mecarbil (cardiac myosin activator) in HFrEF — modest reduction in HF events, no mortality signal.

2021

GOAL-HF1

Safety, pharmacokinetics, and exploratory efficacy of the oral ghrelin receptor agonist AC01 in heart failure with reduced ejection fraction (GOAL-HF1): a randomised, double-blind, placebo-controlled,

2026

HEART-FID

HEART-FID: IV ferric carboxymaltose vs placebo in HFrEF with iron deficiency — no apparent difference in the hierarchical composite of death, HF hospitalization or 6-minute walk distance.

2023

I-PRESERVE

Irbesartan vs placebo in HFpEF — no significant reduction in death or CV hospitalization.

2008

MADIT-CRT

CRT-D in mild HF (NYHA I-II) with EF ≤30% and wide QRS — reduced HF events vs ICD alone.

2009

MADIT-II

Prophylactic ICD in post-MI patients with EF ≤30% — reduced all-cause mortality vs conventional therapy.

2002

MERIT-HF

Metoprolol CR/XL in chronic HFrEF — reduced all-cause mortality, established beta-blocker benefit in HF.

1999

PARADIGM-HF

Sacubitril/valsartan vs enalapril in HFrEF — established ARNI as superior to ACE inhibitor.

2014

PIONEER-HF

Sacubitril/valsartan initiated in-hospital after acute HF — faster NT-proBNP reduction vs enalapril.

2019

PROVE-HF

PROVE-HF (single-arm): after starting sacubitril-valsartan in HFrEF, NT-proBNP fell and the fall tracked reverse remodeling — higher LVEF, smaller LV volumes at 12 months.

2019

RAFT

CRT-D vs ICD in NYHA II-III HF with wide QRS — reduced death and HF hospitalization.

2010

RALES

Spironolactone added to standard therapy in severe HFrEF — reduced mortality, stopped early for benefit.

1999

SAVE

Captopril post-MI in asymptomatic LV dysfunction — reduced mortality and progression to HF.

1992

SCD-HeFT

ICD vs amiodarone vs placebo in HFrEF (ischemic and non-ischemic) — ICD reduced all-cause mortality.

2005

SHIFT

Ivabradine in HFrEF with HR ≥70 on beta-blocker — reduced HF hospitalization and improved symptoms.

2010

SOLVD

Enalapril vs placebo in HFrEF with reduced ejection fraction — reduced mortality and HF hospitalization.

1991

STRONG-HF

High-intensity rapid up-titration of GDMT after acute HF — fewer readmissions and lower mortality.

2022

TOPCAT

Spironolactone vs placebo in HFpEF — no significant reduction in primary composite, regional heterogeneity raised efficacy questions.

2014

Val-HeFT

Valsartan added to standard therapy in HFrEF — reduced combined endpoint of mortality/morbidity.

2001

VALOR-HCM

Mavacamten in patients with obstructive HCM eligible for septal reduction — reduced need for surgery/ablation.

2022

VICTORIA

Vericiguat (soluble guanylate cyclase stimulator) in recent-decompensation HFrEF — reduced CV death and HF hospitalization.

2020

Hypertension

14 trials

ACCOMPLISH

Benazepril/amlodipine vs benazepril/HCTZ in high-risk hypertension — reduced CV events with amlodipine combo.

2008

ACCORD-BP

Intensive (<120) vs standard (<140) BP control in T2DM — no reduction in primary composite, more adverse events.

2010

ALLHAT

First-line thiazide vs ACE inhibitor vs CCB in hypertension — chlorthalidone non-inferior or superior at lower cost.

2002

ASCOT-BPLA

Amlodipine-based vs atenolol-based regimen in hypertension — reduced CV events and all-cause mortality.

2005

HOPE-3

Rosuvastatin + candesartan/HCTZ in intermediate-risk primary prevention — statin reduced events; BP combo only helped if hypertensive.

2016

HYVET

Indapamide ± perindopril in patients ≥80 years with hypertension — reduced stroke and all-cause mortality.

2008

INVEST

Verapamil-based vs atenolol-based therapy in hypertensive CAD — similar primary CV outcomes.

2003

LIFE

Losartan vs atenolol in hypertension with LVH — reduced composite CV endpoint, mainly driven by stroke.

2002

PATHWAY-2

Spironolactone vs bisoprolol vs doxazosin in resistant hypertension — spironolactone most effective.

2015

RADIANCE-HTN

Ultrasound renal denervation vs sham in uncontrolled hypertension — modest BP reduction at 2 months.

2018

SPRINT

Intensive (<120) vs standard (<140) BP control in non-diabetic high-CV-risk adults — fewer CV events and deaths.

2015

STEP (BP)

Intensive (<130) vs standard (<150) SBP in elderly Chinese adults — fewer CV events with intensive control.

2021

SYMPLICITY HTN-3

Renal denervation vs sham in treatment-resistant hypertension — no significant BP reduction at 6 months.

2014

VALUE

Valsartan vs amlodipine in high-risk hypertension — similar primary CV outcomes, amlodipine lowered BP more.

2004

Lipid Management

20 trials

4S

Simvastatin vs placebo in established CHD with hypercholesterolemia — first trial to show statins reduce mortality.

1994

AFCAPS/TexCAPS

Lovastatin in low-LDL adults without CAD — reduced first acute coronary events.

1998

AIM-HIGH

Extended-release niacin added to simvastatin in low HDL CAD — no incremental CV benefit, stopped early.

2011

CLEAR Outcomes

Bempedoic acid in statin-intolerant patients — modest reduction in major CV events.

2023

FOURIER

Evolocumab (PCSK9 inhibitor) added to statin in atherosclerotic disease — large LDL drop, modest event reduction.

2017

HPS

Simvastatin in high-risk patients regardless of baseline LDL — reduced mortality and vascular events.

2002

HPS2-THRIVE

Niacin/laropiprant added to statin — no reduction in major vascular events, more adverse effects.

2014

IMPROVE-IT

Ezetimibe + simvastatin vs simvastatin alone in post-ACS — added LDL lowering yielded modest event reduction.

2015

JUPITER

Rosuvastatin in primary prevention with elevated hs-CRP and normal LDL — large CV event reduction; stopped early for benefit.

2008

Kylo-11

In a phase 1 trial, a single dose of the novel long-acting siRNA Kylo-11 was well-tolerated and produced exceptionally deep, durable reductions in lipoprotein(a) of up to 97% over 48 weeks.

2026

ODYSSEY OUTCOMES

Alirocumab (PCSK9) in post-ACS — reduced major CV events with mortality signal in higher-LDL subgroup.

2018

ORION-10

Inclisiran (siRNA against PCSK9) in ASCVD — sustained LDL reduction with twice-yearly dosing.

2020

ORION-11

Inclisiran in ASCVD or risk equivalents — significant durable LDL-C lowering with twice-yearly injections.

2020

PROMINENT

Pemafibrate vs placebo in T2DM with hypertriglyceridemia — no reduction in major CV events.

2022

PROVE IT-TIMI 22

High-dose atorvastatin vs moderate pravastatin in ACS — intensive statin reduced CV events.

2004

REDUCE-IT

Icosapent ethyl (high-dose EPA) in statin-treated patients with elevated triglycerides — significant CV event reduction.

2019

REVEAL

Anacetrapib added to statin in vascular disease — modest reduction in major coronary events.

2017

STRENGTH

Omega-3 carboxylic acids vs corn oil in high CV risk — no reduction in CV events, stopped early for futility.

2020

TNT

Atorvastatin 80mg vs 10mg in stable CAD — high-dose reduced major CV events.

2005

WOSCOPS

Pravastatin in men with hypercholesterolemia but no MI — reduced CV events in primary prevention.

1995

Atrial Fibrillation

22 trials

ACTIVE-A

Aspirin + clopidogrel vs aspirin alone in AF unsuitable for warfarin — reduced stroke, more bleeding.

2009

ACTIVE-W

Clopidogrel + aspirin vs warfarin in AF — warfarin superior in preventing vascular events.

2006

AFFIRM

Rhythm vs rate control in older atrial fibrillation patients — no survival difference, similar outcomes.

2002

ARISTOTLE

Apixaban vs warfarin in nonvalvular AF — superior stroke prevention, less bleeding, and mortality benefit.

2011

ATHENA

Dronedarone vs placebo in AF/AFL with CV risk — reduced first CV hospitalization or death.

2009

ATLAS ACS 2-TIMI 51

Low-dose rivaroxaban added to antiplatelet therapy after ACS — reduced CV events, more bleeding.

2012

AVERROES

Apixaban vs aspirin in AF patients unsuitable for warfarin — major stroke reduction with similar bleeding.

2011

CABANA

Catheter ablation vs antiarrhythmic drugs in AF — no significant difference in primary composite (ITT analysis).

2019

CASTLE-AF

Catheter ablation vs medical management in AF + HFrEF — lower mortality and HF hospitalization with ablation.

2018

EARLY-AF

Cryoablation vs antiarrhythmic drugs as initial therapy in paroxysmal AF — reduced atrial tachyarrhythmias.

2021

EAST-AFNET 4

Early rhythm control vs usual care in early AF — fewer adverse cardiovascular outcomes.

2020

ENGAGE AF-TIMI 48

Edoxaban 30/60 mg vs warfarin in AF — non-inferior efficacy with less hemorrhagic stroke.

2013

PFA-SHAM

BACKGROUND: Catheter ablation for atrial fibrillation (AF) is one of the most common cardiovascular procedures being performed worldwide.

2026

PRAGUE-17

LAA occlusion vs DOAC in high-risk AF — non-inferior composite of CV events and bleeding.

2020

PREVAIL

Watchman LAA closure vs warfarin in non-valvular AF — improved procedural safety, mixed efficacy endpoints.

2014

PROTECT-AF

Watchman LAA closure vs warfarin in non-valvular AF — non-inferior for stroke, more procedural events early.

2009

PVI-SHAM-AF

In a sham-controlled trial of patients with symptomatic atrial fibrillation, catheter ablation did not significantly improve AF-related quality of life compared to a sham procedure at 6 months, des...

2026

RACE

Rate vs rhythm control in persistent AF — non-inferior outcomes with rate control strategy.

2002

RATE-AF

In older patients with permanent atrial fibrillation and symptoms of heart failure, low-dose digoxin compared with bisoprolol resulted in no significant difference in quality of life at 6 months, but…

2020

RE-LY

Dabigatran 110/150 mg vs warfarin in nonvalvular AF — first DOAC to demonstrate stroke prevention with less hemorrhage.

2009

ROCKET-AF

Rivaroxaban vs warfarin in nonvalvular AF — non-inferior for stroke prevention with similar major bleeding.

2011

STOP-AF

Cryoablation as first-line therapy vs antiarrhythmic drugs in paroxysmal AF — reduced AF recurrence.

2021

Coronary Artery Disease

43 trials

BARI 2D

Revascularization vs medical therapy in T2DM with stable CAD — overall no survival difference; CABG better in three-vessel.

2009

CANTOS

Canakinumab (anti-IL-1β) in post-MI with elevated hsCRP — reduced recurrent CV events independent of lipids.

2017

COLCOT

Low-dose colchicine vs placebo within 30 days of MI — reduced ischemic CV events.

2019

COMPASS

Low-dose rivaroxaban plus aspirin reduced major CV events vs aspirin alone in stable atherosclerotic disease.

2017

COMPLETE

Complete vs culprit-only revascularization in STEMI multivessel disease — reduced CV death/MI.

2019

COURAGE

PCI + OMT vs OMT alone in stable CAD — no mortality benefit from initial PCI, similar MI rates.

2007

CULPRIT-SHOCK

Culprit-lesion-only vs multivessel PCI in cardiogenic shock — culprit-only reduced 30-day death/renal failure.

2017

DANAMI-3-PRIMULTI

FFR-guided complete revascularization vs culprit-only in STEMI multivessel disease — reduced repeat revascularization.

2015

DAPA-MI

Dapagliflozin vs placebo in MI without prior diabetes/HF — improved cardiometabolic outcomes; no MACE difference.

2023

ECLS-SHOCK

VA-ECMO vs control in MI with cardiogenic shock — no mortality benefit, more bleeding/vascular complications.

2023

EMPACT-MI

Empagliflozin vs placebo after acute MI with HF risk factors — no reduction in HF hospitalization or death.

2024

EXCEL

PCI (everolimus-eluting stents) vs CABG in left main CAD with low-intermediate SYNTAX score — noninferior for death, stroke or MI at 3 years.

2016

FAME

FFR-guided PCI vs angiography-guided PCI in multivessel CAD — fewer adverse events with FFR guidance.

2009

FAME 2

FFR-guided PCI + OMT vs OMT alone in stable CAD — lower urgent revascularization with PCI.

2012

FREEDOM

CABG vs PCI in diabetes with multivessel CAD — CABG reduced major CV events and mortality.

2012

GUSTO-I

Accelerated tPA vs streptokinase in acute MI — tPA reduced 30-day mortality with slightly more strokes.

1993

HOST-EXAM

Clopidogrel vs aspirin monotherapy beyond DAPT period after PCI — clopidogrel reduced CV and bleeding events.

2021

IABP-SHOCK II

IABP vs control in MI cardiogenic shock with planned revascularization — no 30-day mortality reduction.

2012

ISAR-REACT 5

Prasugrel vs ticagrelor in ACS — prasugrel reduced primary composite of death, MI, or stroke.

2019

ISCHEMIA

Routine invasive vs optimal medical therapy in stable CAD with moderate ischemia — no mortality benefit from invasive approach.

2020

ISCHEMIA-CKD

Invasive vs conservative strategy in stable CAD with advanced CKD — no reduction in death or MI.

2020

ISIS-2

Streptokinase and aspirin in suspected acute MI — each independently reduced mortality, additive benefit.

1988

LoDoCo2

Low-dose colchicine in chronic coronary disease — reduced major CV events vs placebo.

2020

MASTER-DAPT

1-month vs ≥3-month DAPT in high bleeding risk patients after PCI — non-inferior, less bleeding.

2021

MATRIX

MATRIX 1-year results: radial access lowered net adverse clinical events vs femoral in invasively managed ACS; bivalirudin did not beat unfractionated heparin.

2018

MINT

In patients with acute myocardial infarction and anemia, a liberal blood transfusion strategy did not significantly reduce the 30-day risk of recurrent myocardial infarction or death compared to a re…

2023

NOBLE

PCI vs CABG in left main CAD — CABG superior on composite endpoint.

2016

ONTARGET

Telmisartan vs ramipril vs combo in high-CV-risk patients — non-inferior, combo gave no benefit and more adverse events.

2008

ORBITA

PCI vs sham procedure in stable single-vessel CAD — no significant improvement in exercise time vs sham.

2018

ORBITA-2

PCI vs sham in stable angina off antianginal medications — significant placebo-controlled angina relief from PCI.

2023

PEGASUS-TIMI 54

Long-term ticagrelor added to aspirin 1-3 years post-MI — reduced CV events at cost of bleeding.

2015

PLATO

Ticagrelor vs clopidogrel in ACS — reduced CV death/MI/stroke, slightly more non-CABG bleeding.

2009

RITA-3

Early invasive vs conservative strategy in non-ST ACS — reduced refractory angina and MI long-term.

2002

RIVAL

Radial vs femoral access in ACS undergoing angiography — no overall difference; less major bleeding with radial.

2011

SHOCK

Early revascularization vs initial medical stabilization in MI cardiogenic shock — improved 6-month mortality.

1999

STICH

CABG + medical therapy vs medical therapy alone in ischemic cardiomyopathy — no significant reduction in all-cause death at 5 years; fewer CV deaths and hospitalizations.

2011

STOPDAPT-2

1-month DAPT then clopidogrel monotherapy vs 12-month DAPT after PCI — fewer CV/bleeding events.

2019

SYNTAX

PCI vs CABG in three-vessel/left main CAD — CABG better for complex anatomy at 1 year.

2009

TIMACS

Routine early (<24h) vs delayed intervention in non-ST ACS — early benefit limited to high-risk subgroup.

2009

TIMI 11B

Enoxaparin vs unfractionated heparin in non-ST ACS — reduced composite of death, MI, urgent revascularization.

1999

TRACE

In patients with left ventricular systolic dysfunction following an acute myocardial infarction, the ACE inhibitor trandolapril significantly reduces all-cause mortality, cardiovascular death, and pr…

1995

TRITON-TIMI 38

Prasugrel vs clopidogrel in ACS undergoing PCI — reduced ischemic events, more bleeding.

2007

TWILIGHT

Ticagrelor monotherapy vs ticagrelor+aspirin after 3 months PCI in high-risk patients — reduced bleeding without ischemic penalty.

2019

Valvular Heart Disease

13 trials

AVATAR

Early SAVR vs conservative care in asymptomatic severe AS — reduced composite of mortality and CV events.

2021

COAPT

MitraClip + GDMT vs GDMT alone in HF with severe secondary MR — reduced HF hospitalization and mortality.

2018

EARLY-TAVR

Early TAVR vs clinical surveillance in asymptomatic severe AS — reduced death/stroke/unplanned hospitalization.

2024

EVERESTII

MitraClip vs surgery for significant MR — less effective at MR reduction but safer with similar functional benefits.

2011

Evolut Low Risk

Self-expanding TAVR vs surgical AVR in low-surgical-risk AS — non-inferior 24-month outcomes.

2019

MITRA-FR

MitraClip + medical therapy vs medical therapy alone in HF with secondary MR — no benefit (contrast COAPT).

2018

NOTION-3

In patients with severe aortic stenosis and stable coronary artery disease, performing percutaneous coronary intervention prior to or concurrently with TAVI reduced the composite risk of death, myoca…

2024

PARTNER 1A

TAVR vs surgical AVR in high-surgical-risk severe AS — non-inferior 1-year mortality, paradigm shift.

2011

PARTNER 2A

TAVR vs surgical AVR in intermediate-risk severe AS — non-inferior outcomes, expanded TAVR indications.

2016

PARTNER 3

TAVR vs surgical AVR in low-risk severe AS — superior 1-year outcomes with TAVR.

2019

RECOVERY

Early SAVR vs watchful waiting in asymptomatic very severe AS — reduced operative/CV death.

2020

SURTAVI

Self-expanding TAVR vs SAVR in intermediate risk aortic stenosis — non-inferior all-cause death/stroke.

2017

TRILUMINATE

Tricuspid TEER vs medical therapy in severe symptomatic TR — improved quality of life, neutral hard endpoints.

2023

Perioperative & Antithrombotic

14 trials

AUGUSTUS

Antithrombotic strategies in AF + ACS/PCI — apixaban without aspirin reduced bleeding without raising ischemic events.

2019

BRIDGE

Bridging anticoagulation vs no bridging during warfarin interruption in AF — no thromboembolism reduction, more bleeding.

2015

ENTRUST-AF-PCI

Edoxaban-based dual therapy vs warfarin triple therapy after PCI in AF — non-inferior bleeding endpoint.

2019

ITACS

Abstract Objective To evaluate the effects of intravenous iron on red cell transfusion and recovery after cardiac surgery.

2026

MANAGE

Dabigatran in perioperative MI/myocardial injury after non-cardiac surgery — reduced major vascular complications.

2018

OPTIMA-AF

In patients with atrial fibrillation undergoing percutaneous coronary intervention, one month of dual antithrombotic therapy followed by DOAC monotherapy was non-inferior to 12 months of dual thera...

2026

PAUSE

Standardized DOAC interruption strategy in AF undergoing surgery — low rates of bleeding and thromboembolism.

2019

PERIOP-2

LMWH bridging vs placebo during warfarin interruption in high-risk AF/mechanical valves — no benefit, more bleeding.

2021

PIONEER-AF-PCI

Rivaroxaban-based vs warfarin triple therapy after PCI in AF — reduced clinically significant bleeding.

2016

POISE

Perioperative metoprolol in non-cardiac surgery — fewer MIs but more strokes and total deaths.

2008

POISE-2

Perioperative aspirin and clonidine in non-cardiac surgery — neither reduced CV events; aspirin increased bleeding.

2014

RACER-Knee

In patients with advanced knee osteoarthritis, robotic-arm-assisted total knee replacement did not improve joint awareness or functional outcomes at 12 months compared to conventional surgery, whil...

2026

RE-DUAL PCI

Dabigatran + P2Y12 inhibitor vs warfarin triple therapy after PCI in AF — less bleeding, non-inferior thromboembolism.

2017

WOEST

Warfarin + clopidogrel vs triple therapy after PCI in patients on OAC — reduced bleeding without ischemic penalty.

2013

Cardiac Arrhythmia

5 trials

Diabetes & Cardiometabolic

54 trials

ACCORD (glycemia)

Intensive glucose control to HbA1c <6% increased mortality vs standard in T2D with CVD risk.

2008

ACCORD-Lipid

Adding fenofibrate to simvastatin did not reduce CV events in T2D, except in dyslipidemic subgroup.

2010

ACCORD-MIND

Intensive glucose control did not improve cognitive outcomes vs standard therapy in T2D over 40 months.

2011

ACHIEVE-1

Oral non-peptide GLP-1 receptor agonist orforglipron lowered HbA1c and weight in T2D.

2025

ACHIEVE-2 (orforglipron)

In adults with type 2 diabetes inadequately controlled on metformin, the novel oral non-peptide GLP-1 receptor agonist orforglipron demonstrated superior glycemic control and greater weight loss co...

2026

ADVANCE

Intensive glucose control (HbA1c 6.5%) reduced nephropathy but not major macrovascular events in T2D.

2008

AMPLITUDE-O

Efpeglenatide reduced MACE and renal events in T2D with prior CVD or kidney disease.

2021

ATTAIN-MAINTAIN

Abstract Incretins have improved the management of obesity and its related complications, but maintaining these health benefits requires ongoing administration, which can be challenging.

2026

AWARD-7

AWARD-7: once-weekly dulaglutide vs insulin glargine in T2D with stage 3-4 CKD — noninferior HbA1c lowering, with higher eGFR at 52 weeks.

2018

BEACON

BEACON: bardoxolone methyl in stage 4 CKD with T2D was halted for increased HF and CV events.

2013

CANTATA-SU

Canagliflozin non-inferior to glimepiride for HbA1c reduction with weight loss in T2D on metformin.

2013

CANVAS

Canagliflozin in T2DM with CV risk — CV event benefit but signal for amputations and fractures.

2017

CARMELINA

Linagliptin was non-inferior to placebo for CV and kidney outcomes in T2D at high vascular risk.

2019

CAROLINA

Linagliptin was non-inferior to glimepiride for major adverse cardiovascular events in T2D.

2019

CREDENCE

Canagliflozin in T2DM + diabetic kidney disease — major reduction in renal and CV endpoints.

2019

DAPA-CKD

Dapagliflozin in CKD regardless of diabetes — broad renal, CV, and mortality benefit.

2020

DECLARE-TIMI 58

Dapagliflozin in T2DM with or at risk for CVD — reduced HF hospitalization and renal endpoints.

2018

DEVOTE

Insulin degludec was non-inferior to glargine for MACE and reduced severe hypoglycemia in T2D.

2017

DPP

Lifestyle intervention and metformin reduced incidence of T2D in adults with impaired glucose tolerance.

2002

ELIXA

Lixisenatide was non-inferior to placebo for cardiovascular events in T2D after recent ACS.

2015

EMPA-REG OUTCOME

Empagliflozin in T2DM with established CVD — first SGLT2i to reduce CV death; class-defining trial.

2015

EMPULSE

Empagliflozin initiated during hospitalization for acute HF improved clinical benefit composite at 90 days.

2022

EXAMINE

Alogliptin was non-inferior to placebo for major cardiovascular events in T2D after recent ACS.

2013

FIELD

Fenofibrate did not significantly reduce coronary events in T2D, with possible benefit in dyslipidemic patients.

2005

FLOW

Semaglutide in T2DM with chronic kidney disease — reduced renal and CV events.

2024

GRADE

Liraglutide and insulin glargine best maintained glycemic targets compared with glimepiride or sitagliptin in T2D.

2022

Harmony Outcomes

Albiglutide reduced major adverse CV events in T2D patients with established cardiovascular disease.

2018

LEADER

Liraglutide (GLP-1) in T2DM with high CV risk — reduced CV death and all-cause mortality.

2016

Look AHEAD (remission)

Look AHEAD lifestyle intervention produced T2D remission in a small but meaningful proportion of participants.

2012

LookAHEAD

Intensive lifestyle intervention produced weight loss but did not reduce CV events in overweight/obese T2D.

2013

OASIS-1

Oral semaglutide 50 mg produced 15% weight loss in adults with obesity over 68 weeks.

2023

ORIGIN

Insulin glargine targeting normal fasting glucose did not change CV outcomes in early dysglycemia/T2D.

2012

PIONEER-6

Oral semaglutide was non-inferior to placebo for MACE in T2D at high cardiovascular risk.

2019

REIMAGINE 3

In adults with type 2 diabetes inadequately controlled on basal insulin, the addition of the once-weekly dual agonist cagrilintide–semaglutide (CagriSema) yielded profound improvements in glycemic ...

2026

REWIND

Dulaglutide reduced major adverse cardiovascular events in T2D with established CVD or risk factors.

2019

SAVOR-TIMI 53

Saxagliptin was non-inferior to placebo for ischemic events but increased heart failure hospitalization in T2D.

2013

SCALE

Liraglutide 3.0 mg produced clinically meaningful weight loss vs placebo in adults with obesity over 56 weeks.

2015

SELECT

Semaglutide in non-diabetic overweight/obese patients with CVD — reduced major CV events.

2023

SELECT (kidney)

Semaglutide reduced kidney composite events in overweight/obese adults with established CVD without diabetes.

2024

STEP 1

Once-weekly semaglutide 2.4 mg in obesity — ~15% weight loss vs placebo.

2021

STEP 5

Weekly semaglutide 2.4 mg produced sustained ~15% weight loss over 2 years in adults with obesity.

2022

STEP-HFpEF

Semaglutide in obesity-related HFpEF — improved symptoms, weight, and inflammation.

2023

STEP-HFpEF DM

Semaglutide improved symptoms and weight in obese HFpEF patients with type 2 diabetes.

2024

SURMOUNT-1

Tirzepatide produced 15-22% weight loss in adults with obesity without diabetes over 72 weeks.

2022

SURMOUNT-2

Tirzepatide produced significant weight loss in adults with obesity and type 2 diabetes vs placebo.

2023

SURMOUNT-MAINTAIN

Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial

2026

SURPASS-2

Tirzepatide showed greater HbA1c and weight reduction than semaglutide in T2D on metformin.

2021

SURPASS-3

Tirzepatide produced greater HbA1c and weight reductions vs insulin degludec in T2D inadequately controlled.

2021

SURPASS-4

Tirzepatide produced greater HbA1c/weight reductions vs glargine in T2D with high CV risk; CV outcomes neutral.

2021

SUSTAIN-6

Semaglutide (GLP-1) in T2DM with high CV risk — significant reduction in major CV events.

2016

TECOS

Sitagliptin was non-inferior to placebo for major cardiovascular events in T2D with established CVD.

2015

UKPDS

Intensive vs conventional glycemic control in newly diagnosed T2DM — reduced microvascular complications.

1998

VADT

Intensive vs standard glucose control in long-standing T2D did not reduce major CV events.

2009

VERIFY

Early combination metformin/vildagliptin delayed treatment failure vs sequential therapy in newly diagnosed T2D.

2019

Stroke & Acute Neurology

45 trials

AcT

Tenecteplase non-inferior to alteplase for functional outcomes in acute ischemic stroke within 4.5 hours.

2022

ANNEXA-4

Andexanet alfa effectively reversed anti-factor Xa activity in patients with major bleeding on apixaban/rivaroxaban.

2019

ATACH-II

Intensive systolic BP lowering (110-139 mmHg) did not improve outcomes vs standard in acute ICH.

2016

ATTRACTION (stroke)

In patients with acute ischemic stroke who achieved successful macroscopic endovascular reperfusion, adjunctive tirofiban significantly improved the likelihood of functional independence at 90 days...

2026

CENTAUR

AMX0035 slowed functional decline modestly vs placebo in ALS; later withdrawn after PHOENIX failed.

2020

CHANCE

Clopidogrel plus aspirin for 21 days reduced 90-day stroke vs aspirin alone in minor stroke/TIA in China.

2013

CLARITY

Oral cladribine reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.

2010

CLARITY-AD

Lecanemab anti-amyloid antibody slowed clinical decline in early Alzheimer's disease over 18 months.

2022

CREST-H

In a substudy of the CREST-2 trial, carotid revascularization did not improve cognitive dysfunction over 1 year compared to intensive medical management alone in patients with asymptomatic high-gra...

2026

CRYSTAL-AF

Insertable cardiac monitor detected AF in cryptogenic stroke patients more often than conventional monitoring.

2014

DAWN

Thrombectomy 6-24 hours from last-known-normal with imaging mismatch — substantial functional benefit.

2017

DEFUSE-2

Perfusion-DWI mismatch identified stroke patients more likely to benefit from endovascular reperfusion.

2012

DEFUSE-3

Thrombectomy 6-16 hours in large-vessel occlusion with perfusion mismatch — major outcome improvement.

2018

ECASS-3

IV alteplase between 3 and 4.5 hours improved functional outcomes in acute ischemic stroke vs placebo.

2008

EMERGE/ENGAGE

EMERGE/ENGAGE Phase 3 trials of aducanumab in early Alzheimer's gave mixed results; FDA approved controversially.

2022

ENCHANTED

Low-dose alteplase did not show non-inferiority but reduced symptomatic hemorrhage vs standard dose.

2016

ESCAPE

Rapid endovascular thrombectomy with collaterals selection reduced disability in proximal anterior stroke.

2015

EVOLVE-1

Galcanezumab (anti-CGRP antibody) reduced monthly migraine headache days vs placebo in episodic migraine prevention.

2018

EXTEND

IV alteplase 4.5-9 hours with perfusion imaging selection — improved functional outcomes.

2019

EXTEND-IA

Thrombectomy after IV tPA in patients with perfusion mismatch improved reperfusion and functional outcomes.

2015

FREEDOMS

Oral fingolimod reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.

2010

Frexalimab

In a phase 2 clinical trial, frexalimab, an Fc-engineered anti-CD40L monoclonal antibody, significantly reduced the number of new gadolinium-enhancing brain lesions in patients with relapsing multipl…

2024

INTERACT2

Intensive systolic BP lowering (target <140 mmHg) in acute ICH trended toward better functional outcomes.

2013

IST-3

IV alteplase up to 6 hours did not significantly improve primary outcome but suggested benefit in selected patients.

2012

MCI-186 Study 19

MCI-186-19: IV edaravone slowed functional decline in early-stage ALS with preserved respiratory function.

2017

MR CLEAN

Endovascular thrombectomy within 6 hours improved functional outcomes in proximal anterior circulation stroke.

2015

NINDS

IV alteplase within 3 hours of stroke onset — established acute thrombolysis as standard of care.

1995

OPERA I/II

Ocrelizumab reduced annualized relapse rate vs interferon beta-1a in relapsing-remitting multiple sclerosis.

2017

ORATORIO

Ocrelizumab slowed disability progression vs placebo in primary progressive multiple sclerosis.

2017

POINT

Clopidogrel plus aspirin reduced ischemic events vs aspirin alone after minor stroke or high-risk TIA.

2018

PROMISE-2

IV eptinezumab reduced monthly migraine days vs placebo in chronic migraine prevention.

2020

RESILIENT

Mechanical thrombectomy improved functional outcomes vs medical therapy alone in middle-income country setting.

2020

REVASCAT

Mechanical thrombectomy up to 8 hours improved functional outcomes in proximal anterior circulation occlusion.

2015

SANAD I

SANAD I: lamotrigine had better outcomes than carbamazepine for partial-onset seizures; valproate best for generalized.

2007

SOCRATES

Ticagrelor was not superior to aspirin for prevention of recurrent vascular events after acute ischemic stroke.

2016

SPS3

Dual antiplatelet therapy after lacunar stroke increased bleeding without reducing recurrent stroke.

2012

STRIVE

Erenumab CGRP receptor antagonist reduced monthly migraine days vs placebo in episodic migraine prevention.

2017

SUNBEAM

Ozanimod (S1P modulator) reduced relapse rate vs interferon beta-1a in relapsing-remitting MS.

2019

SWIFT-PRIME

Stent retriever thrombectomy with IV tPA improved functional outcomes vs tPA alone in proximal anterior stroke.

2015

THALES

Ticagrelor plus aspirin reduced stroke/death vs aspirin alone after minor stroke or high-risk TIA.

2020

THRACE

Mechanical thrombectomy after IV tPA improved 3-month functional outcomes in large vessel occlusion stroke.

2016

TIMELESS

Tenecteplase in 4.5-24h window with perfusion mismatch did not improve functional outcomes vs placebo.

2024

TRAILBLAZER-ALZ 2

Donanemab slowed cognitive and functional decline in early symptomatic Alzheimer's with amyloid pathology.

2023

VALOR

Tofersen did not significantly improve ALSFRS-R in SOD1 ALS but lowered neurofilament; conditional FDA approval.

2022

WAKE-UP

IV alteplase in wake-up stroke with DWI-FLAIR mismatch — extended thrombolysis to unknown-onset stroke.

2018

COVID-19 & Vaccines

49 trials

ACTIV-3

Bamlanivimab did not improve outcomes in hospitalized adults with COVID-19 and was discontinued for futility.

2021

ACTT-1

Remdesivir in hospitalized COVID-19 — shorter time to recovery; modest mortality signal.

2020

ACTT-2

Baricitinib plus remdesivir shortened recovery time and improved outcomes vs remdesivir in hospitalized COVID-19.

2021

ASTRAL-1

Sofosbuvir-velpatasvir for 12 weeks achieved 99% SVR12 in HCV genotypes 1, 2, 4, 5 and 6 (genotype 3 was ASTRAL-3).

2015

BNT162b2

Pfizer-BioNTech mRNA COVID-19 vaccine Phase 3 — 95% efficacy.

2020

C-EDGE

Elbasvir-grazoprevir achieved high SVR12 rates in chronic HCV genotype 1, 4, 6 treatment-naive patients.

2015

CAPiTA

PCV13 prevented vaccine-type community-acquired pneumococcal pneumonia in adults aged 65+.

2015

ChAdOx1

ChAdOx1 nCoV-19 adenoviral COVID-19 vaccine showed efficacy against symptomatic disease in pooled Phase 3.

2021

COMET-ICE

COMET-ICE: sotrovimab reduced progression to hospitalization or death in high-risk non-hospitalized COVID-19.

2021

COV-BARRIER

Baricitinib reduced 28-day mortality in hospitalized adults with COVID-19 requiring oxygen.

2021

COVACTA

Tocilizumab in hospitalized severe COVID-19 pneumonia did not improve clinical status at day 28.

2021

DISCOVER

F/TAF non-inferior to F/TDF for HIV PrEP in men and transgender women, with better renal/bone safety.

2020

EMPACTA

Tocilizumab reduced progression to mechanical ventilation or death in hospitalized COVID-19 pneumonia.

2021

ENSEMBLE

Single-dose Ad26.COV2.S vaccine was efficacious against moderate-severe COVID-19 across multiple regions.

2021

EPIC-HR

Nirmatrelvir-ritonavir reduced COVID-19 hospitalization or death by ~89% in high-risk unvaccinated outpatients.

2022

FLU-IVIG

Anti-influenza hyperimmune IV immunoglobulin did not improve outcomes in hospitalized influenza patients.

2019

High-Dose Flu Vaccine (FIM12)

High-dose inactivated influenza vaccine more efficacious than standard dose in adults aged 65 and older.

2014

HPTN-052

Early ART in HIV-positive partner cut HIV transmission to serodiscordant partners by ~96%.

2011

HPTN-083

Injectable cabotegravir every 8 weeks more effective than oral TDF/FTC for HIV PrEP in MSM/TGW.

2021

ION-1

Ledipasvir-sofosbuvir achieved >95% SVR12 in treatment-naive genotype 1 HCV without ribavirin.

2014

iPrEx

Oral TDF/FTC pre-exposure prophylaxis reduced HIV acquisition in men who have sex with men.

2010

MATISSE

Maternal RSVpreF vaccination prevented medically attended severe RSV in infants up to 6 months.

2023

MELODY

Single-dose nirsevimab reduced medically attended RSV lower respiratory illness in healthy infants.

2022

MERINO

Piperacillin-tazobactam inferior to meropenem for ceftriaxone-resistant E. coli/Klebsiella bacteremia mortality.

2018

MOVe-OUT

Molnupiravir reduced hospitalization/death in non-hospitalized adults with mild-moderate COVID-19 at risk.

2022

mRNA-1273

Moderna mRNA COVID-19 vaccine Phase 3 — 94% efficacy.

2020

Nix-TB

BPaL regimen (bedaquiline, pretomanid, linezolid) showed high cure rates in XDR and pretreated MDR-TB.

2020

NVX-CoV2373

Novavax NVX-CoV2373 protein-subunit vaccine showed ~90% efficacy against symptomatic COVID-19 in Phase 3.

2021

OFLOTUB

Gatifloxacin-containing 4-month regimen for drug-susceptible TB was inferior to standard 6-month therapy.

2014

PANORAMIC

Molnupiravir did not reduce hospitalization/death in vaccinated high-risk outpatients with COVID-19.

2022

PARTNER2

PARTNER2: zero linked HIV transmissions among gay serodifferent couples with a virally suppressed partner across 76,088 condomless sex acts (U=U).

2019

PNEUMOSIL

PNEUMOSIL 10-valent pneumococcal conjugate vaccine was non-inferior to Synflorix (PHiD-CV) for IgG responses in Gambian infants.

2020

PREVENT TB

TBTC Study 26 / PREVENT TB: 12-dose weekly rifapentine-isoniazid (3HP) non-inferior to 9-month isoniazid.

2011

PURPOSE-1

Twice-yearly injectable lenacapavir prevented all HIV infections in cisgender women in sub-Saharan Africa.

2024

PURPOSE-2

Twice-yearly lenacapavir reduced HIV incidence vs daily oral TDF/FTC in MSM and gender-diverse populations.

2024

R21

R21/Matrix-M malaria vaccine showed high efficacy against clinical malaria in African children Phase 3.

2023

RECOVERY

Dexamethasone in hospitalized COVID-19 — first proven mortality-reducing therapy in COVID-19.

2021

REMAP-CAP

Tocilizumab and sarilumab improved organ-support-free days in critically ill COVID-19 patients.

2021

REMoxTB

4-month moxifloxacin-containing regimens failed noninferiority to standard 6-month therapy for drug-sensitive TB — more relapses despite faster culture conversion.

2014

RENOIR

Bivalent RSVpreF vaccine prevented RSV-associated lower respiratory illness in adults aged 60+.

2023

RTS,S

RTS,S/AS01 malaria vaccine provided partial protection against clinical and severe malaria in African children.

2015

SMART

Continuous ART was superior to CD4-guided treatment interruption for opportunistic disease and death.

2006

SOLIDARITY

WHO multi-drug COVID-19 treatment trial — remdesivir, HCQ, lopinavir, and IFN-β not effective on mortality.

2020

START

Immediate ART initiation reduced serious AIDS/non-AIDS events in HIV-positive adults with CD4 above 500.

2015

STIMULATE-ICP

The STIMULATE-ICP phase 3 cluster-randomized trial found that while multidisciplinary specialist care improved fatigue in Long COVID patients, adding multi-organ MRI or digital rehabilitation yield...

2026

STREAM

9-month MDR-TB regimen non-inferior to longer WHO regimen with similar safety, more affordable.

2019

Study 31/A5349

Study 31/A5349: 4-month rifapentine/moxifloxacin regimen non-inferior to standard 6-month therapy for drug-susceptible TB.

2021

TEMPRANO

Early ART and isoniazid prophylaxis reduced severe illness/death in HIV-positive adults in West Africa.

2015

ZOE-50/70

Recombinant adjuvanted zoster vaccine (Shingrix) reduced herpes zoster incidence by ~90% in older adults.

2016

Oncology

139 trials

A166

In a phase III trial of patients with pretreated HER2-positive advanced breast cancer, the novel antibody-drug conjugate trastuzumab botidotin significantly prolonged progression-free survival and ...

2026

AAML1831

PURPOSE The Children's Oncology Group phase III clinical trial AAML1831 (ClinicalTrials.gov identifier: NCT04293562 ) evaluated liposomal daunorubicin and cytarabine (CPX-351) versus standard daunorub

2026

ABBV-011

In a first-in-human phase 1 trial, the SEZ6-targeting antibody-drug conjugate ABBV-011 demonstrated a manageable safety profile and encouraging preliminary antitumor activity, yielding a 25% objectiv…

2024

ACHIEVE-2

The ACHIEVE-2 trial demonstrated that 3 months of oxaliplatin-based adjuvant chemotherapy, particularly CAPOX, provided comparable disease-free survival to the standard 6-month regimen for high-risk…

2020

ACT-GI

PURPOSE Chemotherapy-induced thrombocytopenia (CIT) is a challenging and common complication of cytotoxic chemotherapy in patients with GI cancers.

2026

ADAURA

Adjuvant osimertinib in resected EGFR-mutant NSCLC showed major DFS benefit; established adjuvant TKI standard.

2020

AEGEAN

In patients with resectable non-small-cell lung cancer, perioperative treatment consisting of neoadjuvant durvalumab plus chemotherapy followed by adjuvant durvalumab monotherapy significantly improv…

2023

ALCYONE

Daratumumab plus VMP improved PFS in transplant-ineligible newly diagnosed multiple myeloma.

2018

ALEX

Alectinib improved PFS vs crizotinib as first-line therapy in advanced ALK-positive NSCLC.

2017

ALTA-1L

ALTA-1L showed brigatinib improved PFS vs crizotinib in untreated advanced ALK-positive NSCLC.

2020

APHINITY

Adjuvant pertuzumab + trastuzumab + chemo in HER2+ early breast cancer — modest invasive DFS benefit.

2017

ARASENS

Darolutamide added to ADT plus docetaxel improved OS in metastatic hormone-sensitive prostate cancer.

2022

ASCENT

Sacituzumab govitecan improved OS vs chemo in pretreated metastatic triple-negative breast cancer.

2021

ASCOT

The 5-year final analysis of the phase III ASCOT trial confirms that adjuvant S-1 significantly and sustainably improves overall and relapse-free survival compared to observation in patients with c...

2026

ASPEN-06

In a phase 2 trial of patients with pretreated HER2-overexpressing advanced gastric or gastroesophageal junction cancer, the addition of the CD47 inhibitor evorpacept to trastuzumab, ramucirumab, a...

2026

ATTRACTION-2

In patients with heavily pretreated advanced gastric or gastroesophageal junction cancer, third-line or later treatment with the PD-1 inhibitor nivolumab significantly improved overall survival compa…

2017

AURA3

Osimertinib improved PFS vs chemo in T790M-positive EGFR NSCLC after first-line TKI failure.

2017

BART

PURPOSE To report the primary analysis of a multicenter, phase III randomized trial of adjuvant radiotherapy (RT) after chemotherapy and radical cystectomy (RC) in patients with high-risk muscle-invas

2026

BL-B01D1

The first-in-class EGFR-HER3 bispecific antibody-drug conjugate BL-B01D1 demonstrated promising preliminary antitumor activity and a manageable, predominantly hematologic safety profile in heavily pr…

2024

BRUIN

The phase 1/2 BRUIN trial demonstrated that pirtobrutinib, a highly selective noncovalent BTK inhibitor, is safe and highly active in heavily pretreated B-cell malignancies, overcoming acquired resis…

2021

BRUIN CLL-322

In the phase 3 BRUIN CLL-322 trial, adding the noncovalent BTK inhibitor pirtobrutinib to standard fixed-duration venetoclax-rituximab significantly improved progression-free survival in patients w...

2026

CALGB 80405

Cetuximab and bevacizumab plus chemo showed similar OS in first-line KRAS wild-type metastatic colorectal cancer.

2017

CARTITUDE-1

Cilta-cel BCMA CAR-T produced high response rates and durable remissions in heavily pretreated myeloma.

2021

CARTITUDE-4

Cilta-cel improved PFS vs standard care in lenalidomide-refractory multiple myeloma after 1-3 lines.

2023

CASTOR

Daratumumab added to bortezomib/dex improved PFS in relapsed or refractory multiple myeloma.

2016

CheckMate-067

Nivolumab + ipilimumab or nivolumab alone vs ipilimumab in untreated advanced melanoma — longer progression-free survival; OS data immature.

2015

CheckMate-067

Nivolumab plus ipilimumab improved OS vs ipilimumab alone in untreated advanced melanoma; landmark combo immunotherapy.

2017

CheckMate-214

Nivolumab plus ipilimumab improved OS vs sunitinib in intermediate/poor-risk advanced renal cell carcinoma.

2018

CheckMate-577

Adjuvant nivolumab doubled disease-free survival in resected esophageal/GEJ cancer with residual disease.

2021

CheckMate-649

Nivolumab plus chemo improved OS vs chemo alone in advanced HER2-negative gastric/GEJ adenocarcinoma.

2021

CheckMate-816

Neoadjuvant nivolumab plus chemo before resection in NSCLC improved pCR and event-free survival.

2022

CHOP

The SWOG 8516 trial demonstrated that third-generation intensive chemotherapy regimens were neither more effective nor less toxic than the standard CHOP regimen for advanced non-Hodgkin's lymphoma.

1993

CLEAR

Lenvatinib plus pembrolizumab improved PFS and OS vs sunitinib in advanced renal cell carcinoma.

2021

CLEOPATRA

Pertuzumab + trastuzumab + docetaxel in first-line HER2+ metastatic breast cancer — longer PFS; the survival benefit was reported in 2015.

2012

CodeBreaK 100

Sotorasib showed clinical activity in KRAS G12C-mutated advanced NSCLC, first KRAS-targeted approval.

2021

COMBI-AD

Adjuvant dabrafenib plus trametinib improved relapse-free survival in BRAF-mutant resected stage III melanoma.

2017

COMMIT

PURPOSE Immunotherapy for frontline mismatch repair–deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC) is effective;

2026

COMPETE

[177Lu]Lu-edotreotide versus everolimus for gastroenteropancreatic neuroendocrine tumours (COMPETE): a phase 3, multicentre, randomised, open-label, superiority trial

2026

CROSS

Neoadjuvant chemoradiation improved OS vs surgery alone in resectable esophageal cancer.

2012

CROWN

Lorlatinib improved PFS vs crizotinib in previously untreated advanced ALK-positive NSCLC.

2020

CUPISCO

In patients with unfavorable cancer of unknown primary who achieved disease control after induction chemotherapy, comprehensive genomic profiling followed by molecularly guided therapy significantly…

2024

DART

PURPOSE Concurrent platinum-based chemotherapy and radiation therapy (cCRT) followed by consolidative durvalumab is the standard of care (SoC) for fit patients with inoperable, locally advanced non–sm

2026

DESTINY-Breast03

Trastuzumab deruxtecan vs T-DM1 in HER2+ metastatic breast cancer showed dramatic PFS and OS benefit.

2022

DESTINY-Breast04

T-DXd improved OS in HER2-low metastatic breast cancer, establishing HER2-low as a treatable category.

2022

EAQ171CD

A multicenter randomized controlled trial demonstrating that a virtual sustained tobacco treatment program consisting of telehealth counseling and nicotine replacement therapy significantly increas...

2026

ECHELON-1

Brentuximab vedotin plus AVD improved PFS over ABVD in previously untreated stage III/IV Hodgkin lymphoma.

2018

EMBRACA

Talazoparib (PARP inhibitor) in BRCA+ metastatic breast cancer — improved PFS vs chemotherapy.

2018

EMILIA

T-DM1 improved PFS and OS vs lapatinib/capecitabine in HER2+ advanced breast cancer pretreated.

2012

eNRGy

In the phase 2 eNRGy trial, zenocutuzumab, a bispecific antibody targeting HER2 and HER3, demonstrated a 30% overall response rate with durable anti-tumor activity and a highly favorable safety profi…

2025

EORTC 22033

The mature 13-year follow-up of a phase III trial in high-risk low-grade glioma found no significant overall survival difference between initial temozolomide and standard radiotherapy, reinforcing ...

2026

EPCORE NHL-1

Epcoritamab CD20-CD3 bispecific induced durable responses in relapsed/refractory large B-cell lymphoma.

2023

Euro-EWING99

A large randomized non-inferiority trial demonstrating that cyclophosphamide is non-inferior to ifosfamide as consolidation therapy for standard-risk localized Ewing sarcoma, offering a more favorabl…

2014

EV-302

Enfortumab vedotin plus pembrolizumab improved OS and PFS vs chemo in untreated advanced urothelial carcinoma.

2023

FIND

PURPOSE We hypothesized that a dynamic surveillance strategy guided by circulating tumor DNA (ctDNA) methylation would increase the rate of curative-intent therapy for recurrence in patients with nonm

2026

FLAURA

First-line osimertinib vs first-generation EGFR-TKIs in EGFR-mutant NSCLC — longer PFS (18.9 vs 10.2 months); OS immature at this analysis.

2017

FLAURA2

Osimertinib plus chemo improved PFS vs osimertinib alone in untreated EGFR-mutated advanced NSCLC.

2023

frontMIND

The addition of tafasitamab and lenalidomide to standard R-CHOP therapy significantly prolonged progression-free survival in patients with previously untreated, high-risk diffuse large B-cell lymph...

2026

GMMG-HD7

Mass spectrometry (MS) offers a minimally invasive approach for detecting monoclonal proteins in multiple myeloma (MM), but large prospective evaluations remain limited.

2026

HER2CLIMB

Tucatinib added to trastuzumab/capecitabine in HER2+ metastatic breast cancer improved OS, including brain metastases.

2020

IDEA

IDEA pooled analysis suggested 3 months of adjuvant CAPOX non-inferior to 6 months in low-risk stage III colon cancer.

2018

IMbrave150

Atezolizumab plus bevacizumab improved OS and PFS vs sorafenib in unresectable hepatocellular carcinoma.

2020

IMpassion130

Atezolizumab + nab-paclitaxel in PD-L1+ TNBC — PFS benefit (controversial OS).

2018

IMpower010

Adjuvant atezolizumab after resection in stage II-IIIA NSCLC improved DFS in PD-L1 positive disease.

2021

JCOG1008

In patients with postoperative high-risk locally advanced head and neck squamous cell carcinoma, chemoradiotherapy with weekly cisplatin was noninferior to standard 3-weekly cisplatin for overall sur…

2022

KarMMa

Ide-cel BCMA CAR-T showed deep responses in heavily pretreated relapsed/refractory multiple myeloma.

2021

KATHERINE

T-DM1 vs trastuzumab in residual HER2+ breast cancer after neoadjuvant therapy — major iDFS benefit.

2019

KEYNOTE-024

First-line pembrolizumab vs chemotherapy in PD-L1-high NSCLC — major overall survival benefit.

2016

KEYNOTE-054

Adjuvant pembrolizumab improved recurrence-free survival in resected high-risk stage III melanoma.

2018

KEYNOTE-189

First-line pembrolizumab + chemo in non-squamous NSCLC — significant OS and PFS gain.

2018

KEYNOTE-407

First-line pembrolizumab + chemo in squamous NSCLC — improved overall survival.

2018

KEYNOTE-426

Pembrolizumab plus axitinib improved OS and PFS vs sunitinib in advanced renal cell carcinoma.

2019

KEYNOTE-522

Neoadjuvant pembrolizumab plus chemo in early triple-negative breast cancer improved pCR and event-free survival.

2020

KEYNOTE-590

Pembrolizumab plus chemo improved OS in advanced esophageal and esophagogastric junction cancer.

2021

KEYNOTE-826

Pembrolizumab plus chemo improved OS in persistent, recurrent, or metastatic cervical cancer.

2021

KRYSTAL-1

Adagrasib produced a 42.9% response rate in previously treated KRAS G12C-mutated NSCLC, with intracranial activity.

2022

LATITUDE

Abiraterone plus prednisone added to ADT improved OS in newly diagnosed high-risk metastatic hormone-sensitive prostate cancer.

2017

LITESPARK-011

Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial

2026

MAGIC

Perioperative ECF chemotherapy improved OS vs surgery alone in resectable gastric/lower esophageal cancer.

2006

MAGNITUDE

Niraparib plus abiraterone improved PFS in HRR-positive metastatic castration-resistant prostate cancer.

2022

MAIA

Daratumumab plus Rd improved PFS and depth of response in transplant-ineligible newly diagnosed myeloma; OS immature at this report.

2019

MajesTEC-1

Teclistamab BCMA-CD3 bispecific produced durable responses in heavily pretreated relapsed/refractory myeloma.

2022

MARIPOSA

Amivantamab plus lazertinib improved PFS vs osimertinib in first-line EGFR-mutated advanced NSCLC.

2023

MATTERHORN

In patients with resectable gastric or gastroesophageal junction adenocarcinoma, the addition of perioperative durvalumab to standard FLOT chemotherapy significantly improved event-free survival comp…

2025

MINDACT

MammaPrint genomic test identified breast cancer patients who could safely skip adjuvant chemotherapy.

2016

MONALEESA-2

Ribociclib plus letrozole prolonged PFS in postmenopausal HR+/HER2- advanced breast cancer; OS benefit was reported in 2022.

2016

monarchE

Adjuvant abemaciclib plus endocrine therapy in high-risk HR+/HER2- early breast cancer improved invasive DFS.

2020

MOSAIC

Adjuvant FOLFOX improved DFS over 5-FU/LV in resected stage II/III colon cancer; established standard.

2004

NAPOLI-3

NALIRIFOX improved OS vs gem/nab-paclitaxel in untreated metastatic pancreatic adenocarcinoma.

2023

NEMIO

PURPOSE To evaluate the efficacy and safety of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) combined with durvalumab ± tremelimumab in patients with muscle-inv

2026

neoCARHP

The neoCARHP trial investigators clarify their creatinine assay and carboplatin dosing methodology, affirming that the higher rate of hematologic toxicity in the carboplatin arm was due to expected...

2026

NETTER-1

177Lu-DOTATATE PRRT in advanced midgut neuroendocrine tumors — established peptide receptor radionuclide therapy.

2017

NOAH

Neoadjuvant trastuzumab plus chemo improved event-free survival in HER2+ locally advanced breast cancer.

2010

NOVA

Niraparib maintenance improved PFS in platinum-sensitive recurrent ovarian cancer, regardless of BRCA status.

2016

OlympiA

One year of adjuvant olaparib improved invasive DFS in BRCA-mutated high-risk early breast cancer.

2021

PACIFIC

Durvalumab consolidation after chemoradiation in unresectable stage III NSCLC — markedly longer PFS; OS reported later.

2017

PACIFIC-2

Concurrent durvalumab with chemoradiation in unresectable stage III NSCLC did not improve PFS vs sequential.

2024

PALOMA-2

Palbociclib plus letrozole improved PFS in postmenopausal HR+/HER2- metastatic breast cancer first-line.

2016

PALOMA-3

Palbociclib plus fulvestrant improved PFS in pretreated HR+/HER2- advanced breast cancer.

2015

PAOLA-1

Olaparib plus bevacizumab maintenance improved PFS in advanced ovarian cancer, especially HRD-positive.

2019

PATHFINDER

A prospective cohort study demonstrating the clinical feasibility of using a blood-based multi-cancer early detection (MCED) test to screen for multiple cancers simultaneously and direct subsequent d…

2023

PCDC

An international prospective biomarker study developed and validated PANXEON, a liquid biopsy assay combining a 10-miRNA signature with CA 19-9, demonstrating high sensitivity for detecting early-s...

2026

PIVOTAL

In patients with resectable stage III melanoma, neoadjuvant intralesional administration of daromun (L19IL2 and L19TNF) prior to surgery significantly prolonged recurrence-free and distant metastasis…

2025

POLARIX

Pola-R-CHP improved PFS vs R-CHOP in previously untreated intermediate/high-risk DLBCL.

2022

POSEIDON

Tremelimumab plus durvalumab plus chemo improved OS vs chemo alone in untreated metastatic NSCLC.

2022

PRADA

In women receiving adjuvant anthracycline-containing therapy for early breast cancer, concomitant treatment with the angiotensin receptor blocker candesartan protected against early decline in left v…

2016

PRIMA

Niraparib maintenance improved PFS in newly diagnosed advanced ovarian cancer regardless of BRCA status.

2019

PRODIGE 23

Neoadjuvant FOLFIRINOX before chemoradiation improved DFS in locally advanced rectal cancer.

2021

PROfound

Olaparib improved PFS and OS vs enzalutamide/abi in HRR-mutated metastatic castration-resistant prostate cancer.

2020

RADICAL

PURPOSE Bone metastases (BM) occur in approximately 30% of patients with metastatic renal cell carcinoma (mRCC) and are associated with poor survival and symptomatic skeletal events (SSEs).

2026

RAPIDO

Short-course RT followed by chemo before surgery reduced disease-related treatment failure in rectal cancer.

2020

RCTS

PURPOSE Clinical data for first-line combination of antibody-drug conjugates (ADC) and immune checkpoint inhibitors in human epidermal growth factor receptor 2 (HER2)–overexpressing advanced gastric o

2026

REIMAGINE

In a prospective community-based screening study, upfront biparametric MRI detected a substantial number of clinically significant prostate cancers in men with normal PSA levels, demonstrating the fe…

2023

RELATIVITY-047

Relatlimab plus nivolumab (LAG-3 + PD-1) improved PFS vs nivolumab alone in untreated advanced melanoma.

2022

RELIGHT

The phase III RELIGHT trial demonstrated that adding the novel anti-PD-L1/TGF-β bispecific antibody retlirafusp alfa to first-line CAPOX chemotherapy significantly improved overall survival and pro...

2026

ROAM/EORTC-1308

In patients with completely resected WHO grade 2 atypical meningioma, early adjuvant radiotherapy significantly reduces the risk of tumor recurrence and improves 5-year disease-free survival compar...

2026

RUBY

Dostarlimab plus chemo improved PFS in advanced endometrial cancer, especially dMMR/MSI-H tumors.

2023

RxPONDER

Postmenopausal women with HR+ node-positive breast cancer and low recurrence score could omit chemotherapy.

2021

SHARE

PURPOSE To compare hypofractionated radiotherapy (RT) with conventional RT for treating biochemical recurrence following radical prostatectomy.

2026

SOLO-1

Olaparib maintenance dramatically improved PFS in newly diagnosed BRCA-mutated advanced ovarian cancer.

2018

STAMPEDE (docetaxel)

STAMPEDE: adding docetaxel to first-line hormone therapy improved survival in advanced prostate cancer; zoledronic acid did not.

2016

STELLAR

In patients with locally advanced rectal cancer, short-term radiotherapy followed by neoadjuvant chemotherapy (total neoadjuvant therapy) was non-inferior to standard long-term chemoradiotherapy for…

2022

SU2C-SARC032

Tumor-informed personalized ctDNA profiling successfully detected baseline circulating tumor DNA in 85% of patients with localized soft tissue sarcomas and provided independent prognostic informati...

2026

SUCCESSOR-2

Mezigdomide, carfilzomib, and dexamethasone versus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma (SUCCESSOR-2): a phase 3, open-label, randomised controlled tr

2026

SWOG 8794

In men with pathologically advanced prostate cancer following radical prostatectomy, adjuvant radiotherapy significantly reduces the risk of PSA relapse and disease recurrence, with a trend toward im…

2006

SWOG/NRG S1914

The phase 3 SWOG/NRG S1914 trial demonstrated that adding the immune checkpoint inhibitor atezolizumab to stereotactic body radiation therapy (SBRT) in high-risk, early-stage, medically inoperable ...

2026

TAILORx

Endocrine therapy alone non-inferior to chemo-endocrine in HR+/HER2- node-negative breast cancer with mid-range RS.

2018

TITAN

Apalutamide added to ADT improved OS and radiographic PFS in metastatic castration-sensitive prostate cancer.

2019

TOPAZ-1

Durvalumab plus chemo improved OS vs chemo alone in advanced biliary tract cancer first-line.

2022

TOURMALINE-MM1

Ixazomib added to Rd improved PFS in relapsed/refractory multiple myeloma.

2016

Trastuzumab

The addition of the anti-HER2 monoclonal antibody trastuzumab to standard chemotherapy significantly improved time to progression and overall survival in women with HER2-overexpressing metastatic bre…

2001

TRAVERSE

PURPOSE Treatment options for clear cell renal cell carcinoma (ccRCC) refractory to immune checkpoint inhibitors (ICIs) and targeted therapy are needed.

2026

TRIANGLE

In younger patients with mantle cell lymphoma, adding ibrutinib to frontline induction and maintenance significantly improved failure-free survival, and standard ASCT was not superior to an ibrutinib…

2024

TROPiCS-02

Sacituzumab govitecan improved PFS vs chemotherapy in pretreated HR+/HER2- metastatic breast cancer; OS not yet mature in this report.

2022

TROPION-Lung01

Dato-DXd improved PFS modestly vs docetaxel in previously treated advanced NSCLC, especially nonsquamous.

2023

TXI

In an international, multicenter randomized trial, the use of Texture and Color Enhancement Imaging (TXI) during colonoscopy significantly increased the adenoma detection rate compared to standard hi…

2023

WSG TP-II

The WSG-TP-II trial found that neoadjuvant de-escalated chemotherapy (paclitaxel) combined with dual HER2 blockade achieved a significantly higher pathological complete response rate than endocrine t…

2023

X-ACT

Adjuvant capecitabine non-inferior to 5-FU/LV in stage III colon cancer with better tolerability.

2005

ZUMA-1

Axi-cel CAR-T showed durable responses in refractory large B-cell lymphoma, leading to FDA approval.

2017

ZUMA-7

Axi-cel improved event-free survival vs standard care as second-line therapy in relapsed/refractory LBCL.

2022

Critical Care

37 trials

65 trial

Permissive hypotension (MAP 60-65) did not significantly reduce 90-day mortality vs usual care in older sepsis patients.

2020

6S

Hydroxyethyl starch 130/0.42 increased death and renal replacement therapy vs Ringer's acetate in severe sepsis.

2012

ADRENAL

Continuous infusion hydrocortisone did not reduce 90-day mortality vs placebo in septic shock requiring vasopressors.

2018

ANDROMEDA-SHOCK

Capillary refill vs lactate-guided resuscitation in septic shock — trend toward lower mortality with CRT-guided care.

2019

APROCCHSS

Hydrocortisone plus fludrocortisone reduced 90-day mortality in septic shock with high severity scores.

2018

ARISE

Early goal-directed therapy did not reduce 90-day mortality vs usual care in septic shock.

2014

ARMA (ARDSNet)

Low tidal volume ventilation (6 mL/kg) in ARDS — reduced mortality; defined modern ventilator strategy.

2000

ART

Lung recruitment maneuver and titrated PEEP increased mortality vs low-PEEP strategy in moderate-severe ARDS.

2017

ASTARTÉ

In patients with bacteremia caused by third-generation cephalosporin-resistant Enterobacterales, targeted therapy with intravenous temocillin was non-inferior to carbapenems for 28-day clinical suc...

2026

BaSICS

Balanced solution did not significantly reduce 90-day mortality vs saline in heterogeneous Brazilian ICU patients.

2021

CESAR

ECMO referral in severe respiratory failure — improved 6-month outcomes.

2009

CHEST

Hydroxyethyl starch 130/0.4 increased renal replacement therapy vs saline in critically ill adults.

2012

CORTICUS

Hydrocortisone did not improve survival vs placebo in septic shock regardless of corticotropin test response.

2008

CRASH-2

Early IV tranexamic acid reduced all-cause and bleeding-related mortality in adult trauma patients with hemorrhage.

2010

CRASH-3

Tranexamic acid reduced head-injury-related death in patients with mild/moderate TBI treated early.

2019

EOLIA

Early VV-ECMO did not significantly reduce 60-day mortality vs conventional care in very severe ARDS.

2018

EPaNIC

Late initiation of parenteral nutrition was superior to early in adult ICU patients; less infection and faster recovery.

2011

NICE-SUGAR

Intensive glucose control (81-108 mg/dL) increased mortality vs conventional (<180 mg/dL) in adult ICU patients.

2009

PARAMEDIC2

In adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival and Return of Spontaneous Circulation (ROSC) than placebo, but did not…

2018

PEPTIC

Pantoprazole did not significantly reduce 90-day mortality vs histamine-2 blocker in ICU patients receiving mechanical ventilation.

2020

PLUS

Balanced multielectrolyte solution did not significantly reduce 90-day mortality vs saline in critically ill adults.

2022

ProCESS

Protocolized early goal-directed therapy in sepsis — no mortality benefit vs usual care.

2014

ProMISe

EGDT did not reduce 90-day mortality vs usual resuscitation in early septic shock in UK NHS hospitals.

2015

PROSEVA

Early prolonged prone positioning reduced 28-day mortality in severe ARDS (PaO2/FiO2 <150).

2013

RATE (ECLS)

The RATE trial demonstrated that in adults undergoing ECMO, low-dose unfractionated heparin and therapeutic low-molecular-weight heparin were non-inferior to standard-dose unfractionated heparin fo...

2026

RESHAP-ED

Primary-contact, physiotherapist-led care for uncomplicated musculoskeletal conditions in the emergency department significantly reduces length of stay and improves patient flow without compromisin...

2026

ROSE

Routine early cisatracurium did not reduce 90-day mortality vs usual care with lighter sedation in moderate-severe ARDS.

2019

SAFE

4% albumin and 0.9% saline produced similar 28-day mortality in heterogeneous ICU population.

2004

SALT-ED

Balanced crystalloids reduced major adverse kidney events vs saline in non-critically ill ED patients.

2018

SNAP

In the largest randomized adaptive platform trial for Staphylococcus aureus bacteremia, cefazolin was found to be noninferior to standard antistaphylococcal penicillins for 90-day mortality while sig…

2026

SNAP (PSSA)

The SNAP trial demonstrated that benzylpenicillin halved the risk of acute kidney injury and showed a high probability of non-inferiority for mortality compared to flucloxacillin or cloxacillin in ...

2026

SOAP-II

Norepinephrine reduced arrhythmias vs dopamine in shock; mortality similar overall but dopamine worse in cardiogenic shock.

2010

SUP-ICU

Pantoprazole did not significantly reduce 90-day mortality vs placebo in adult ICU patients at risk for GI bleeding.

2018

TARGET

Energy-dense (1.5 kcal/mL) enteral nutrition did not improve 90-day mortality vs routine in mechanically ventilated adults.

2018

TRICC

Restrictive RBC transfusion (Hgb 7) was non-inferior or superior to liberal (Hgb 10) in critically ill adults.

1999

TRISS

Restrictive transfusion threshold (Hgb 7) similar mortality to liberal (Hgb 9) in septic shock patients.

2014

VASST

Adding vasopressin to norepinephrine did not reduce mortality vs norepinephrine alone in septic shock.

2008

Pulmonary Disease

29 trials

AMBITION

Initial combination ambrisentan plus tadalafil reduced clinical failure vs monotherapy in treatment-naive PAH.

2015

ASCEND

Pirfenidone in IPF (confirmatory trial) — slowed decline, reduced mortality.

2014

BOREAS

Dupilumab reduced exacerbations and improved lung function in COPD with type 2 inflammation (elevated eosinophils).

2023

CAPACITY

Pirfenidone in idiopathic pulmonary fibrosis — slowed lung function decline.

2011

CHEST-1

Riociguat improved exercise capacity and hemodynamics in inoperable CTEPH or persistent PH after PEA.

2013

DREAM

Mepolizumab anti-IL-5 reduced eosinophilic asthma exacerbations vs placebo in severe disease.

2012

ETHOS

Budesonide/glycopyrrolate/formoterol triple therapy reduced exacerbations and all-cause mortality vs dual LAMA/LABA in COPD.

2020

FLAME

LABA/LAMA reduced COPD exacerbations vs ICS/LABA in patients with history of exacerbations.

2016

GRIPHON

Selexipag oral prostacyclin receptor agonist reduced morbidity/mortality events in pulmonary arterial hypertension.

2015

IMPACT

Fluticasone/umeclidinium/vilanterol triple therapy reduced exacerbations vs dual therapy in symptomatic COPD.

2018

INBUILD

Nintedanib slowed FVC decline in progressive fibrosing non-IPF interstitial lung diseases.

2019

INPULSIS-1

Nintedanib in IPF — slowed FVC decline.

2014

INPULSIS-2

Nintedanib slowed annual FVC decline in idiopathic pulmonary fibrosis with manageable side effects.

2014

MENSA

Mepolizumab reduced clinically significant asthma exacerbations in patients with severe eosinophilic asthma.

2014

NAVIGATOR

Tezepelumab anti-TSLP reduced annualized asthma exacerbations vs placebo in severe uncontrolled asthma regardless of phenotype.

2021

NOTUS

NOTUS confirmed dupilumab reduced exacerbations in COPD with type 2 inflammation, supporting FDA approval.

2024

ORBEX

In a randomized trial of high-risk preschool children, prophylactic oral administration of the bacterial lysate OM-85 for 24 months did not significantly reduce the time to first wheezing lower res...

2026

PATENT-1

Riociguat soluble guanylate cyclase stimulator improved exercise capacity and clinical outcomes in PAH.

2013

POET-COPD

Tiotropium reduced time to first moderate-severe COPD exacerbation vs salmeterol over 1 year.

2011

QUEST

Dupilumab reduced exacerbations and improved FEV1 in moderate-severe uncontrolled asthma, especially eosinophilic.

2018

SENSCIS

Nintedanib slowed FVC decline in systemic sclerosis-associated interstitial lung disease over 52 weeks.

2019

SERAPHIN

Macitentan reduced morbidity/mortality composite vs placebo in pulmonary arterial hypertension.

2013

SIRIUS

Mepolizumab reduced oral corticosteroid dose while maintaining asthma control in severe eosinophilic asthma.

2014

STELLAR

Sotatercept added to background therapy improved 6-minute walk distance in pulmonary arterial hypertension.

2023

TORCH

Salmeterol/fluticasone combination did not significantly reduce all-cause mortality vs placebo in moderate-severe COPD.

2007

TRAVERSE

Long-term dupilumab maintained efficacy and safety in patients with moderate-severe asthma over 96 weeks.

2022

TRIBUTE

Single-inhaler triple therapy reduced moderate-severe exacerbations vs LAMA/LABA in symptomatic COPD with prior exacerbations.

2018

UPLIFT

Tiotropium did not slow FEV1 decline but improved lung function and quality of life over 4 years in COPD.

2008

WISDOM

Stepwise withdrawal of ICS in severe COPD did not increase exacerbations but slightly worsened lung function.

2014

Women’s Health

4 trials

Obstetrics

17 trials

ALPS

Antenatal betamethasone in late preterm pregnancy reduced respiratory morbidity in newborns vs placebo.

2016

ARRIVE

Elective induction at 39 weeks vs expectant management in low-risk nulliparous women — fewer cesareans without harm.

2018

ASPRE

Low-dose aspirin in high-risk women reduced preterm preeclampsia vs placebo in first-trimester screening cohort.

2017

BEAM

Antenatal magnesium sulfate reduced moderate-severe cerebral palsy in surviving infants born very preterm.

2008

Cerclage (Owen 2009)

Ultrasound-indicated cerclage for cervix <25 mm after prior preterm birth — no significant drop in birth <35 weeks overall; fewer previable births and perinatal deaths.

2009

CHAP

Treating mild chronic hypertension to BP <140/90 reduced adverse pregnancy outcomes without harming fetal growth.

2022

CHIPS

Tight blood pressure control in non-severe pregnancy hypertension did not improve perinatal outcomes vs less tight.

2015

GBS3

GBS3 process-outcomes paper: universal late-pregnancy GBS testing was feasible and acceptable in UK maternity units; this paper does not report clinical effectiveness.

2026

HAPO

HAPO: maternal glucose levels below diabetes thresholds were associated with adverse pregnancy outcomes.

2008

MAGPIE

Magnesium sulfate halved the risk of eclampsia in women with preeclampsia compared with placebo.

2002

Meis 17P

17-OHPC weekly reduced recurrent preterm birth vs placebo in women with prior spontaneous preterm delivery.

2003

MOMS

Prenatal repair of myelomeningocele reduced need for VP shunt and improved motor outcomes vs postnatal repair.

2011

PRISM

Vaginal progesterone did not improve overall live birth rate but benefitted women with prior miscarriages.

2019

PROLONG

PROLONG: 17-OHPC did not reduce recurrent preterm birth in women with prior spontaneous preterm delivery.

2019

STRIDER

Sildenafil did not improve outcomes in severe early-onset fetal growth restriction and was associated with neonatal harm.

2018

Term Breech

Planned cesarean delivery reduced perinatal mortality/morbidity vs planned vaginal birth for term breech presentation.

2000

WOMAN

Tranexamic acid reduced death due to bleeding in women with postpartum hemorrhage when given early.

2017

Primary Prevention

36 trials

ALLHAT-LLT

Pravastatin did not significantly reduce all-cause mortality vs usual care in hypertensive adults aged 55+.

2002

ASPREE

Low-dose aspirin in healthy elderly primary prevention — no benefit, increased bleeding.

2018

D2d

Vitamin D3 4000 IU daily did not significantly reduce progression to T2D in adults with prediabetes.

2019

DASH

DASH dietary pattern lowered systolic and diastolic blood pressure substantially in adults with high-normal/Stage 1 HTN.

1997

DASH-Sodium

Reducing sodium intake plus DASH diet lowered blood pressure more than either intervention alone.

2001

DCCT

Intensive vs conventional glycemic control in T1DM — major reduction in microvascular complications.

1993

EAGLES

Varenicline and bupropion did not increase neuropsychiatric adverse events vs NRT/placebo in smokers.

2016

FINGER

The FINGER trial demonstrated that a 2-year multidomain lifestyle intervention significantly improves or maintains cognitive functioning in older adults at increased risk for dementia compared to reg…

2015

HOPE

Ramipril reduced CV events in patients with vascular disease or diabetes plus a CV risk factor.

2000

ISLEND-2

Switching virologically suppressed adults with HIV-1 to a once-weekly oral single-tablet regimen of islatravir and lenacapavir is non-inferior to continuing daily standard-of-care antiretroviral th...

2026

LATA

In virologically suppressed adolescents living with HIV in sub-Saharan Africa, switching to long-acting injectable cabotegravir-rilpivirine every 8 weeks was superior to daily oral standard-of-care...

2026

LatAm-FINGERS

The LatAm-FINGERS trial demonstrated that a culturally tailored, 2-year multidomain lifestyle intervention significantly improved global cognition compared to standard health advice in at-risk olde...

2026

MEGA

Pravastatin reduced coronary events in Japanese adults with hypercholesterolemia without prior CVD.

2006

NELSON

Volume CT lung cancer screening reduced lung cancer mortality in male former and current smokers in Europe.

2020

NICUSeq

In acutely ill infants with suspected genetic diseases, early whole-genome sequencing doubled the rate of diagnostic yield and significantly increased actionable changes in clinical management compar…

2021

NLST

NLST: low-dose CT screening reduced lung cancer mortality by 20% vs chest x-ray in high-risk smokers.

2011

NORDICC

Invitation to colonoscopy reduced colorectal cancer risk modestly; effect attenuated by limited uptake.

2022

PLCO

PLCO: organized annual PSA screening showed no prostate-cancer mortality benefit vs usual care at 13 years (RR 1.09, 95% CI 0.87-1.36).

2012

PolyIran

Polypill containing aspirin, statin, and antihypertensives reduced major CV events in Iranian rural cohort.

2019

PREDIMED

Mediterranean diet with olive oil or nuts reduced major CV events vs low-fat diet in high-risk adults.

2013

PREDIMED-Plus

PREDIMED-Plus interim analysis: an intensive energy-reduced Mediterranean diet program improved diet adherence at 12 months vs usual advice; this paper reports no cardiovascular outcomes.

2019

PROSPER

Pravastatin reduced coronary events in older adults at risk for CVD with mixed effects in primary prevention.

2002

PURE

PURE study: high carbohydrate intake associated with higher mortality; total fat with lower mortality globally.

2017

REFIT2

A large phase 3 trial demonstrated that a single administration of faecal microbiota transplantation via rectal enema provided no clinical benefit over an autologous placebo in patients with modera...

2026

SHEP

Antihypertensive drug treatment of isolated systolic hypertension in elderly reduced stroke and CV events.

1991

SPRINT-MIND

Intensive BP control (target <120 mmHg) reduced MCI and combined MCI/dementia but not probable dementia alone.

2019

SSaSS

SSaSS: salt substitute with reduced sodium and added potassium reduced stroke and CV events in rural China.

2021

STAREE

STAREE: atorvastatin 40 mg in adults 70+ without CVD lowered major cardiovascular events (HR 0.70) but did not extend disability-free survival (HR 0.94) over 5.9 years.

2026

TIPS-3

TIPS-3: polypill plus aspirin reduced CV events vs placebo in intermediate-risk adults without CVD.

2021

TONE

Weight loss and sodium reduction reduced need for antihypertensive medication in older adults with HTN.

1998

VITAL

Vitamin D3 2000 IU and omega-3 1g daily did not reduce major CV events or cancer vs placebo over 5 years.

2019

VITAL-Bone

Vitamin D3 2000 IU daily did not reduce fractures in generally healthy older adults without low BMD or vitamin D deficiency.

2022

VITAL-DEP

Vitamin D3 2000 IU daily did not reduce incident depression in older adults without baseline depression.

2020

VITAL-Rhythm

Vitamin D and omega-3 did not reduce incidence of atrial fibrillation in primary prevention population.

2020

WHI Diet

Low-fat dietary pattern did not reduce breast cancer, colorectal cancer, or CHD over 8 years in postmenopausal women.

2006

WHISH

WHISH design and baseline paper: a pragmatic physical-activity trial in 49,331 older women; this paper reports no outcomes.

2021

Other

1 trial

Cardiology

172 trials

4S

Simvastatin vs placebo in established CHD with hypercholesterolemia — first trial to show statins reduce mortality.

1994

A-HeFT

Hydralazine/isosorbide dinitrate in self-identified Black patients with HFrEF — reduced mortality, stopped early.

2004

ACCOMPLISH

Benazepril/amlodipine vs benazepril/HCTZ in high-risk hypertension — reduced CV events with amlodipine combo.

2008

ACCORD-BP

Intensive (<120) vs standard (<140) BP control in T2DM — no reduction in primary composite, more adverse events.

2010

ACTIVE-A

Aspirin + clopidogrel vs aspirin alone in AF unsuitable for warfarin — reduced stroke, more bleeding.

2009

ACTIVE-W

Clopidogrel + aspirin vs warfarin in AF — warfarin superior in preventing vascular events.

2006

AFCAPS/TexCAPS

Lovastatin in low-LDL adults without CAD — reduced first acute coronary events.

1998

AFFIRM

Rhythm vs rate control in older atrial fibrillation patients — no survival difference, similar outcomes.

2002

AIM-HIGH

Extended-release niacin added to simvastatin in low HDL CAD — no incremental CV benefit, stopped early.

2011

AIRE

Ramipril in post-MI patients with HF — reduced all-cause mortality vs placebo.

1993

ALLHAT

First-line thiazide vs ACE inhibitor vs CCB in hypertension — chlorthalidone non-inferior or superior at lower cost.

2002

ARISTOTLE

Apixaban vs warfarin in nonvalvular AF — superior stroke prevention, less bleeding, and mortality benefit.

2011

ASCOT-BPLA

Amlodipine-based vs atenolol-based regimen in hypertension — reduced CV events and all-cause mortality.

2005

ATHENA

Dronedarone vs placebo in AF/AFL with CV risk — reduced first CV hospitalization or death.

2009

ATLAS ACS 2-TIMI 51

Low-dose rivaroxaban added to antiplatelet therapy after ACS — reduced CV events, more bleeding.

2012

ATTR-ACT

Tafamidis in ATTR cardiomyopathy — reduced all-cause mortality and CV hospitalization vs placebo.

2018

AUGUSTUS

Antithrombotic strategies in AF + ACS/PCI — apixaban without aspirin reduced bleeding without raising ischemic events.

2019

AVATAR

Early SAVR vs conservative care in asymptomatic severe AS — reduced composite of mortality and CV events.

2021

AVERROES

Apixaban vs aspirin in AF patients unsuitable for warfarin — major stroke reduction with similar bleeding.

2011

BARI 2D

Revascularization vs medical therapy in T2DM with stable CAD — overall no survival difference; CABG better in three-vessel.

2009

BRIDGE

Bridging anticoagulation vs no bridging during warfarin interruption in AF — no thromboembolism reduction, more bleeding.

2015

CABANA

Catheter ablation vs antiarrhythmic drugs in AF — no significant difference in primary composite (ITT analysis).

2019

CANTOS

Canakinumab (anti-IL-1β) in post-MI with elevated hsCRP — reduced recurrent CV events independent of lipids.

2017

CARE-HF

CRT-P vs medical therapy in HFrEF with wide QRS — reduced mortality and HF hospitalization.

2005

CAST

Encainide/flecainide vs placebo to suppress PVCs post-MI — increased mortality; pivotal negative trial.

1991

CASTLE-AF

Catheter ablation vs medical management in AF + HFrEF — lower mortality and HF hospitalization with ablation.

2018

CHAMPION

Implantable hemodynamic monitor (CardioMEMS) in NYHA III HF — reduced HF hospitalizations.

2011

CHARM-Added

Candesartan added to ACE inhibitor in HFrEF — modestly reduced CV death and HF hospitalization.

2003

CHARM-Alternative

Candesartan in ACE inhibitor-intolerant HFrEF — reduced CV death/HF hospitalization vs placebo.

2003

CIBIS-II

Bisoprolol vs placebo in moderate-severe HFrEF — reduced all-cause mortality, stopped early for benefit.

1999

CLEAR Outcomes

Bempedoic acid in statin-intolerant patients — modest reduction in major CV events.

2023

COAPT

MitraClip + GDMT vs GDMT alone in HF with severe secondary MR — reduced HF hospitalization and mortality.

2018

COLCOT

Low-dose colchicine vs placebo within 30 days of MI — reduced ischemic CV events.

2019

COMPANION

CRT-P and CRT-D vs medical therapy in advanced HF with wide QRS — reduced hospitalization/death.

2004

COMPASS

Low-dose rivaroxaban plus aspirin reduced major CV events vs aspirin alone in stable atherosclerotic disease.

2017

COMPLETE

Complete vs culprit-only revascularization in STEMI multivessel disease — reduced CV death/MI.

2019

CONSENSUS

Enalapril vs placebo in NYHA IV HF — first trial to show ACE inhibitor mortality benefit, stopped early.

1987

COPERNICUS

Carvedilol in severe HFrEF — reduced all-cause mortality, expanded beta-blocker use to severe HF.

2001

COURAGE

PCI + OMT vs OMT alone in stable CAD — no mortality benefit from initial PCI, similar MI rates.

2007

CULPRIT-SHOCK

Culprit-lesion-only vs multivessel PCI in cardiogenic shock — culprit-only reduced 30-day death/renal failure.

2017

DANAMI-3-PRIMULTI

FFR-guided complete revascularization vs culprit-only in STEMI multivessel disease — reduced repeat revascularization.

2015

DANISH

Prophylactic ICD in non-ischemic systolic HF — no significant all-cause mortality reduction.

2016

DAPA-HF

Dapagliflozin (SGLT2i) added to GDMT in HFrEF — first SGLT2i to show benefit regardless of diabetes status.

2019

DAPA-MI

Dapagliflozin vs placebo in MI without prior diabetes/HF — improved cardiometabolic outcomes; no MACE difference.

2023

DELIVER

Dapagliflozin in HFpEF (LVEF >40%) — extended SGLT2i benefit across the EF spectrum.

2022

EARLY-AF

Cryoablation vs antiarrhythmic drugs as initial therapy in paroxysmal AF — reduced atrial tachyarrhythmias.

2021

EARLY-TAVR

Early TAVR vs clinical surveillance in asymptomatic severe AS — reduced death/stroke/unplanned hospitalization.

2024

EAST-AFNET 4

Early rhythm control vs usual care in early AF — fewer adverse cardiovascular outcomes.

2020

ECLS-SHOCK

VA-ECMO vs control in MI with cardiogenic shock — no mortality benefit, more bleeding/vascular complications.

2023

EMPACT-MI

Empagliflozin vs placebo after acute MI with HF risk factors — no reduction in HF hospitalization or death.

2024

EMPEROR-Preserved

Empagliflozin in HFpEF — first SGLT2i shown to reduce HF hospitalization regardless of ejection fraction.

2021

EMPEROR-Reduced

Empagliflozin in HFrEF — confirmed SGLT2i class benefit, reduced HF hospitalization and CV death.

2020

EMPHASIS-HF

Eplerenone in mild HFrEF (NYHA II) — extended MRA benefit to less severe heart failure.

2011

ENGAGE AF-TIMI 48

Edoxaban 30/60 mg vs warfarin in AF — non-inferior efficacy with less hemorrhagic stroke.

2013

ENTRUST-AF-PCI

Edoxaban-based dual therapy vs warfarin triple therapy after PCI in AF — non-inferior bleeding endpoint.

2019

EPHESUS

Eplerenone in post-MI patients with LV dysfunction and HF — reduced all-cause mortality and CV events.

2003

EVERESTII

MitraClip vs surgery for significant MR — less effective at MR reduction but safer with similar functional benefits.

2011

Evolut Low Risk

Self-expanding TAVR vs surgical AVR in low-surgical-risk AS — non-inferior 24-month outcomes.

2019

EXCEL

PCI (everolimus-eluting stents) vs CABG in left main CAD with low-intermediate SYNTAX score — noninferior for death, stroke or MI at 3 years.

2016

EXPLORER-HCM

Mavacamten vs placebo in symptomatic obstructive HCM — improved exercise capacity and LVOT gradient.

2020

FAME

FFR-guided PCI vs angiography-guided PCI in multivessel CAD — fewer adverse events with FFR guidance.

2009

FAME 2

FFR-guided PCI + OMT vs OMT alone in stable CAD — lower urgent revascularization with PCI.

2012

FINEARTS-HF

Finerenone (non-steroidal MRA) in HFmrEF/HFpEF — reduced CV death and HF events.

2024

FOURIER

Evolocumab (PCSK9 inhibitor) added to statin in atherosclerotic disease — large LDL drop, modest event reduction.

2017

FREEDOM

CABG vs PCI in diabetes with multivessel CAD — CABG reduced major CV events and mortality.

2012

GALACTIC-HF

Omecamtiv mecarbil (cardiac myosin activator) in HFrEF — modest reduction in HF events, no mortality signal.

2021

GOAL-HF1

Safety, pharmacokinetics, and exploratory efficacy of the oral ghrelin receptor agonist AC01 in heart failure with reduced ejection fraction (GOAL-HF1): a randomised, double-blind, placebo-controlled,

2026

GUSTO-I

Accelerated tPA vs streptokinase in acute MI — tPA reduced 30-day mortality with slightly more strokes.

1993

HEART-FID

HEART-FID: IV ferric carboxymaltose vs placebo in HFrEF with iron deficiency — no apparent difference in the hierarchical composite of death, HF hospitalization or 6-minute walk distance.

2023

HOPE-3

Rosuvastatin + candesartan/HCTZ in intermediate-risk primary prevention — statin reduced events; BP combo only helped if hypertensive.

2016

HOST-EXAM

Clopidogrel vs aspirin monotherapy beyond DAPT period after PCI — clopidogrel reduced CV and bleeding events.

2021

HPS

Simvastatin in high-risk patients regardless of baseline LDL — reduced mortality and vascular events.

2002

HPS2-THRIVE

Niacin/laropiprant added to statin — no reduction in major vascular events, more adverse effects.

2014

HYVET

Indapamide ± perindopril in patients ≥80 years with hypertension — reduced stroke and all-cause mortality.

2008

I-PRESERVE

Irbesartan vs placebo in HFpEF — no significant reduction in death or CV hospitalization.

2008

IABP-SHOCK II

IABP vs control in MI cardiogenic shock with planned revascularization — no 30-day mortality reduction.

2012

IMPROVE-IT

Ezetimibe + simvastatin vs simvastatin alone in post-ACS — added LDL lowering yielded modest event reduction.

2015

INVEST

Verapamil-based vs atenolol-based therapy in hypertensive CAD — similar primary CV outcomes.

2003

ISAR-REACT 5

Prasugrel vs ticagrelor in ACS — prasugrel reduced primary composite of death, MI, or stroke.

2019

ISCHEMIA

Routine invasive vs optimal medical therapy in stable CAD with moderate ischemia — no mortality benefit from invasive approach.

2020

ISCHEMIA-CKD

Invasive vs conservative strategy in stable CAD with advanced CKD — no reduction in death or MI.

2020

ISIS-2

Streptokinase and aspirin in suspected acute MI — each independently reduced mortality, additive benefit.

1988

ITACS

Abstract Objective To evaluate the effects of intravenous iron on red cell transfusion and recovery after cardiac surgery.

2026

JUPITER

Rosuvastatin in primary prevention with elevated hs-CRP and normal LDL — large CV event reduction; stopped early for benefit.

2008

Kylo-11

In a phase 1 trial, a single dose of the novel long-acting siRNA Kylo-11 was well-tolerated and produced exceptionally deep, durable reductions in lipoprotein(a) of up to 97% over 48 weeks.

2026

LIFE

Losartan vs atenolol in hypertension with LVH — reduced composite CV endpoint, mainly driven by stroke.

2002

LoDoCo2

Low-dose colchicine in chronic coronary disease — reduced major CV events vs placebo.

2020

MADIT-CRT

CRT-D in mild HF (NYHA I-II) with EF ≤30% and wide QRS — reduced HF events vs ICD alone.

2009

MADIT-II

Prophylactic ICD in post-MI patients with EF ≤30% — reduced all-cause mortality vs conventional therapy.

2002

MADIT-RIT

High-rate or delayed ICD therapy vs conventional programming — reduced inappropriate shocks and mortality.

2012

MANAGE

Dabigatran in perioperative MI/myocardial injury after non-cardiac surgery — reduced major vascular complications.

2018

MASTER-DAPT

1-month vs ≥3-month DAPT in high bleeding risk patients after PCI — non-inferior, less bleeding.

2021

MATRIX

MATRIX 1-year results: radial access lowered net adverse clinical events vs femoral in invasively managed ACS; bivalirudin did not beat unfractionated heparin.

2018

MERIT-HF

Metoprolol CR/XL in chronic HFrEF — reduced all-cause mortality, established beta-blocker benefit in HF.

1999

MINT

In patients with acute myocardial infarction and anemia, a liberal blood transfusion strategy did not significantly reduce the 30-day risk of recurrent myocardial infarction or death compared to a re…

2023

MITRA-FR

MitraClip + medical therapy vs medical therapy alone in HF with secondary MR — no benefit (contrast COAPT).

2018

NOBLE

PCI vs CABG in left main CAD — CABG superior on composite endpoint.

2016

NOTION-3

In patients with severe aortic stenosis and stable coronary artery disease, performing percutaneous coronary intervention prior to or concurrently with TAVI reduced the composite risk of death, myoca…

2024

ODYSSEY OUTCOMES

Alirocumab (PCSK9) in post-ACS — reduced major CV events with mortality signal in higher-LDL subgroup.

2018

ONTARGET

Telmisartan vs ramipril vs combo in high-CV-risk patients — non-inferior, combo gave no benefit and more adverse events.

2008

OPTIC

Amiodarone + beta-blocker vs sotalol vs beta-blocker alone for ICD shock prevention — amiodarone combo most effective.

2006

OPTIMA-AF

In patients with atrial fibrillation undergoing percutaneous coronary intervention, one month of dual antithrombotic therapy followed by DOAC monotherapy was non-inferior to 12 months of dual thera...

2026

ORBITA

PCI vs sham procedure in stable single-vessel CAD — no significant improvement in exercise time vs sham.

2018

ORBITA-2

PCI vs sham in stable angina off antianginal medications — significant placebo-controlled angina relief from PCI.

2023

ORION-10

Inclisiran (siRNA against PCSK9) in ASCVD — sustained LDL reduction with twice-yearly dosing.

2020

ORION-11

Inclisiran in ASCVD or risk equivalents — significant durable LDL-C lowering with twice-yearly injections.

2020

PARADIGM-HF

Sacubitril/valsartan vs enalapril in HFrEF — established ARNI as superior to ACE inhibitor.

2014

PARTITA

VT ablation after first appropriate ICD shock vs continued medical therapy — reduced death/VT storm.

2022

PARTNER 1A

TAVR vs surgical AVR in high-surgical-risk severe AS — non-inferior 1-year mortality, paradigm shift.

2011

PARTNER 2A

TAVR vs surgical AVR in intermediate-risk severe AS — non-inferior outcomes, expanded TAVR indications.

2016

PARTNER 3

TAVR vs surgical AVR in low-risk severe AS — superior 1-year outcomes with TAVR.

2019

PATHWAY-2

Spironolactone vs bisoprolol vs doxazosin in resistant hypertension — spironolactone most effective.

2015

PAUSE

Standardized DOAC interruption strategy in AF undergoing surgery — low rates of bleeding and thromboembolism.

2019

PEGASUS-TIMI 54

Long-term ticagrelor added to aspirin 1-3 years post-MI — reduced CV events at cost of bleeding.

2015

PERIOP-2

LMWH bridging vs placebo during warfarin interruption in high-risk AF/mechanical valves — no benefit, more bleeding.

2021

PFA-SHAM

BACKGROUND: Catheter ablation for atrial fibrillation (AF) is one of the most common cardiovascular procedures being performed worldwide.

2026

PIONEER-AF-PCI

Rivaroxaban-based vs warfarin triple therapy after PCI in AF — reduced clinically significant bleeding.

2016

PIONEER-HF

Sacubitril/valsartan initiated in-hospital after acute HF — faster NT-proBNP reduction vs enalapril.

2019

PLATO

Ticagrelor vs clopidogrel in ACS — reduced CV death/MI/stroke, slightly more non-CABG bleeding.

2009

POISE

Perioperative metoprolol in non-cardiac surgery — fewer MIs but more strokes and total deaths.

2008

POISE-2

Perioperative aspirin and clonidine in non-cardiac surgery — neither reduced CV events; aspirin increased bleeding.

2014

PRAGUE-17

LAA occlusion vs DOAC in high-risk AF — non-inferior composite of CV events and bleeding.

2020

PREVAIL

Watchman LAA closure vs warfarin in non-valvular AF — improved procedural safety, mixed efficacy endpoints.

2014

PROMINENT

Pemafibrate vs placebo in T2DM with hypertriglyceridemia — no reduction in major CV events.

2022

PROTECT-AF

Watchman LAA closure vs warfarin in non-valvular AF — non-inferior for stroke, more procedural events early.

2009

PROVE IT-TIMI 22

High-dose atorvastatin vs moderate pravastatin in ACS — intensive statin reduced CV events.

2004

PROVE-HF

PROVE-HF (single-arm): after starting sacubitril-valsartan in HFrEF, NT-proBNP fell and the fall tracked reverse remodeling — higher LVEF, smaller LV volumes at 12 months.

2019

PVI-SHAM-AF

In a sham-controlled trial of patients with symptomatic atrial fibrillation, catheter ablation did not significantly improve AF-related quality of life compared to a sham procedure at 6 months, des...

2026

RACE

Rate vs rhythm control in persistent AF — non-inferior outcomes with rate control strategy.

2002

RACER-Knee

In patients with advanced knee osteoarthritis, robotic-arm-assisted total knee replacement did not improve joint awareness or functional outcomes at 12 months compared to conventional surgery, whil...

2026

RADIANCE-HTN

Ultrasound renal denervation vs sham in uncontrolled hypertension — modest BP reduction at 2 months.

2018

RAFT

CRT-D vs ICD in NYHA II-III HF with wide QRS — reduced death and HF hospitalization.

2010

RALES

Spironolactone added to standard therapy in severe HFrEF — reduced mortality, stopped early for benefit.

1999

RATE-AF

In older patients with permanent atrial fibrillation and symptoms of heart failure, low-dose digoxin compared with bisoprolol resulted in no significant difference in quality of life at 6 months, but…

2020

RE-DUAL PCI

Dabigatran + P2Y12 inhibitor vs warfarin triple therapy after PCI in AF — less bleeding, non-inferior thromboembolism.

2017

RE-LY

Dabigatran 110/150 mg vs warfarin in nonvalvular AF — first DOAC to demonstrate stroke prevention with less hemorrhage.

2009

RECOVERY

Early SAVR vs watchful waiting in asymptomatic very severe AS — reduced operative/CV death.

2020

REDUCE-IT

Icosapent ethyl (high-dose EPA) in statin-treated patients with elevated triglycerides — significant CV event reduction.

2019

REVEAL

Anacetrapib added to statin in vascular disease — modest reduction in major coronary events.

2017

RITA-3

Early invasive vs conservative strategy in non-ST ACS — reduced refractory angina and MI long-term.

2002

RIVAL

Radial vs femoral access in ACS undergoing angiography — no overall difference; less major bleeding with radial.

2011

ROCKET-AF

Rivaroxaban vs warfarin in nonvalvular AF — non-inferior for stroke prevention with similar major bleeding.

2011

SAVE

Captopril post-MI in asymptomatic LV dysfunction — reduced mortality and progression to HF.

1992

SCD-HeFT

ICD vs amiodarone vs placebo in HFrEF (ischemic and non-ischemic) — ICD reduced all-cause mortality.

2005

SHIFT

Ivabradine in HFrEF with HR ≥70 on beta-blocker — reduced HF hospitalization and improved symptoms.

2010

SHOCK

Early revascularization vs initial medical stabilization in MI cardiogenic shock — improved 6-month mortality.

1999

SOLVD

Enalapril vs placebo in HFrEF with reduced ejection fraction — reduced mortality and HF hospitalization.

1991

SPRINT

Intensive (<120) vs standard (<140) BP control in non-diabetic high-CV-risk adults — fewer CV events and deaths.

2015

STEP (BP)

Intensive (<130) vs standard (<150) SBP in elderly Chinese adults — fewer CV events with intensive control.

2021

STICH

CABG + medical therapy vs medical therapy alone in ischemic cardiomyopathy — no significant reduction in all-cause death at 5 years; fewer CV deaths and hospitalizations.

2011

STOP-AF

Cryoablation as first-line therapy vs antiarrhythmic drugs in paroxysmal AF — reduced AF recurrence.

2021

STOPDAPT-2

1-month DAPT then clopidogrel monotherapy vs 12-month DAPT after PCI — fewer CV/bleeding events.

2019

STRENGTH

Omega-3 carboxylic acids vs corn oil in high CV risk — no reduction in CV events, stopped early for futility.

2020

STRONG-HF

High-intensity rapid up-titration of GDMT after acute HF — fewer readmissions and lower mortality.

2022

SURTAVI

Self-expanding TAVR vs SAVR in intermediate risk aortic stenosis — non-inferior all-cause death/stroke.

2017

SYMPLICITY HTN-3

Renal denervation vs sham in treatment-resistant hypertension — no significant BP reduction at 6 months.

2014

SYNTAX

PCI vs CABG in three-vessel/left main CAD — CABG better for complex anatomy at 1 year.

2009

TIMACS

Routine early (<24h) vs delayed intervention in non-ST ACS — early benefit limited to high-risk subgroup.

2009

TIMI 11B

Enoxaparin vs unfractionated heparin in non-ST ACS — reduced composite of death, MI, urgent revascularization.

1999

TNT

Atorvastatin 80mg vs 10mg in stable CAD — high-dose reduced major CV events.

2005

TOPCAT

Spironolactone vs placebo in HFpEF — no significant reduction in primary composite, regional heterogeneity raised efficacy questions.

2014

TRACE

In patients with left ventricular systolic dysfunction following an acute myocardial infarction, the ACE inhibitor trandolapril significantly reduces all-cause mortality, cardiovascular death, and pr…

1995

TRILUMINATE

Tricuspid TEER vs medical therapy in severe symptomatic TR — improved quality of life, neutral hard endpoints.

2023

TRITON-TIMI 38

Prasugrel vs clopidogrel in ACS undergoing PCI — reduced ischemic events, more bleeding.

2007

TWILIGHT

Ticagrelor monotherapy vs ticagrelor+aspirin after 3 months PCI in high-risk patients — reduced bleeding without ischemic penalty.

2019

Val-HeFT

Valsartan added to standard therapy in HFrEF — reduced combined endpoint of mortality/morbidity.

2001

VALOR-HCM

Mavacamten in patients with obstructive HCM eligible for septal reduction — reduced need for surgery/ablation.

2022

VALUE

Valsartan vs amlodipine in high-risk hypertension — similar primary CV outcomes, amlodipine lowered BP more.

2004

VANISH

Catheter ablation vs escalated antiarrhythmic therapy in recurrent VT — reduced composite of death/VT storm/ICD shocks.

2016

VICTORIA

Vericiguat (soluble guanylate cyclase stimulator) in recent-decompensation HFrEF — reduced CV death and HF hospitalization.

2020

WOEST

Warfarin + clopidogrel vs triple therapy after PCI in patients on OAC — reduced bleeding without ischemic penalty.

2013

WOSCOPS

Pravastatin in men with hypercholesterolemia but no MI — reduced CV events in primary prevention.

1995

Endocrinology

54 trials

ACCORD (glycemia)

Intensive glucose control to HbA1c <6% increased mortality vs standard in T2D with CVD risk.

2008

ACCORD-Lipid

Adding fenofibrate to simvastatin did not reduce CV events in T2D, except in dyslipidemic subgroup.

2010

ACCORD-MIND

Intensive glucose control did not improve cognitive outcomes vs standard therapy in T2D over 40 months.

2011

ACHIEVE-1

Oral non-peptide GLP-1 receptor agonist orforglipron lowered HbA1c and weight in T2D.

2025

ACHIEVE-2 (orforglipron)

In adults with type 2 diabetes inadequately controlled on metformin, the novel oral non-peptide GLP-1 receptor agonist orforglipron demonstrated superior glycemic control and greater weight loss co...

2026

ADVANCE

Intensive glucose control (HbA1c 6.5%) reduced nephropathy but not major macrovascular events in T2D.

2008

AMPLITUDE-O

Efpeglenatide reduced MACE and renal events in T2D with prior CVD or kidney disease.

2021

ATTAIN-MAINTAIN

Abstract Incretins have improved the management of obesity and its related complications, but maintaining these health benefits requires ongoing administration, which can be challenging.

2026

AWARD-7

AWARD-7: once-weekly dulaglutide vs insulin glargine in T2D with stage 3-4 CKD — noninferior HbA1c lowering, with higher eGFR at 52 weeks.

2018

BEACON

BEACON: bardoxolone methyl in stage 4 CKD with T2D was halted for increased HF and CV events.

2013

CANTATA-SU

Canagliflozin non-inferior to glimepiride for HbA1c reduction with weight loss in T2D on metformin.

2013

CANVAS

Canagliflozin in T2DM with CV risk — CV event benefit but signal for amputations and fractures.

2017

CARMELINA

Linagliptin was non-inferior to placebo for CV and kidney outcomes in T2D at high vascular risk.

2019

CAROLINA

Linagliptin was non-inferior to glimepiride for major adverse cardiovascular events in T2D.

2019

CREDENCE

Canagliflozin in T2DM + diabetic kidney disease — major reduction in renal and CV endpoints.

2019

DAPA-CKD

Dapagliflozin in CKD regardless of diabetes — broad renal, CV, and mortality benefit.

2020

DECLARE-TIMI 58

Dapagliflozin in T2DM with or at risk for CVD — reduced HF hospitalization and renal endpoints.

2018

DEVOTE

Insulin degludec was non-inferior to glargine for MACE and reduced severe hypoglycemia in T2D.

2017

DPP

Lifestyle intervention and metformin reduced incidence of T2D in adults with impaired glucose tolerance.

2002

ELIXA

Lixisenatide was non-inferior to placebo for cardiovascular events in T2D after recent ACS.

2015

EMPA-REG OUTCOME

Empagliflozin in T2DM with established CVD — first SGLT2i to reduce CV death; class-defining trial.

2015

EMPULSE

Empagliflozin initiated during hospitalization for acute HF improved clinical benefit composite at 90 days.

2022

EXAMINE

Alogliptin was non-inferior to placebo for major cardiovascular events in T2D after recent ACS.

2013

FIELD

Fenofibrate did not significantly reduce coronary events in T2D, with possible benefit in dyslipidemic patients.

2005

FLOW

Semaglutide in T2DM with chronic kidney disease — reduced renal and CV events.

2024

GRADE

Liraglutide and insulin glargine best maintained glycemic targets compared with glimepiride or sitagliptin in T2D.

2022

Harmony Outcomes

Albiglutide reduced major adverse CV events in T2D patients with established cardiovascular disease.

2018

LEADER

Liraglutide (GLP-1) in T2DM with high CV risk — reduced CV death and all-cause mortality.

2016

Look AHEAD (remission)

Look AHEAD lifestyle intervention produced T2D remission in a small but meaningful proportion of participants.

2012

LookAHEAD

Intensive lifestyle intervention produced weight loss but did not reduce CV events in overweight/obese T2D.

2013

OASIS-1

Oral semaglutide 50 mg produced 15% weight loss in adults with obesity over 68 weeks.

2023

ORIGIN

Insulin glargine targeting normal fasting glucose did not change CV outcomes in early dysglycemia/T2D.

2012

PIONEER-6

Oral semaglutide was non-inferior to placebo for MACE in T2D at high cardiovascular risk.

2019

REIMAGINE 3

In adults with type 2 diabetes inadequately controlled on basal insulin, the addition of the once-weekly dual agonist cagrilintide–semaglutide (CagriSema) yielded profound improvements in glycemic ...

2026

REWIND

Dulaglutide reduced major adverse cardiovascular events in T2D with established CVD or risk factors.

2019

SAVOR-TIMI 53

Saxagliptin was non-inferior to placebo for ischemic events but increased heart failure hospitalization in T2D.

2013

SCALE

Liraglutide 3.0 mg produced clinically meaningful weight loss vs placebo in adults with obesity over 56 weeks.

2015

SELECT

Semaglutide in non-diabetic overweight/obese patients with CVD — reduced major CV events.

2023

SELECT (kidney)

Semaglutide reduced kidney composite events in overweight/obese adults with established CVD without diabetes.

2024

STEP 1

Once-weekly semaglutide 2.4 mg in obesity — ~15% weight loss vs placebo.

2021

STEP 5

Weekly semaglutide 2.4 mg produced sustained ~15% weight loss over 2 years in adults with obesity.

2022

STEP-HFpEF

Semaglutide in obesity-related HFpEF — improved symptoms, weight, and inflammation.

2023

STEP-HFpEF DM

Semaglutide improved symptoms and weight in obese HFpEF patients with type 2 diabetes.

2024

SURMOUNT-1

Tirzepatide produced 15-22% weight loss in adults with obesity without diabetes over 72 weeks.

2022

SURMOUNT-2

Tirzepatide produced significant weight loss in adults with obesity and type 2 diabetes vs placebo.

2023

SURMOUNT-MAINTAIN

Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial

2026

SURPASS-2

Tirzepatide showed greater HbA1c and weight reduction than semaglutide in T2D on metformin.

2021

SURPASS-3

Tirzepatide produced greater HbA1c and weight reductions vs insulin degludec in T2D inadequately controlled.

2021

SURPASS-4

Tirzepatide produced greater HbA1c/weight reductions vs glargine in T2D with high CV risk; CV outcomes neutral.

2021

SUSTAIN-6

Semaglutide (GLP-1) in T2DM with high CV risk — significant reduction in major CV events.

2016

TECOS

Sitagliptin was non-inferior to placebo for major cardiovascular events in T2D with established CVD.

2015

UKPDS

Intensive vs conventional glycemic control in newly diagnosed T2DM — reduced microvascular complications.

1998

VADT

Intensive vs standard glucose control in long-standing T2D did not reduce major CV events.

2009

VERIFY

Early combination metformin/vildagliptin delayed treatment failure vs sequential therapy in newly diagnosed T2D.

2019

Neurology

45 trials

AcT

Tenecteplase non-inferior to alteplase for functional outcomes in acute ischemic stroke within 4.5 hours.

2022

ANNEXA-4

Andexanet alfa effectively reversed anti-factor Xa activity in patients with major bleeding on apixaban/rivaroxaban.

2019

ATACH-II

Intensive systolic BP lowering (110-139 mmHg) did not improve outcomes vs standard in acute ICH.

2016

ATTRACTION (stroke)

In patients with acute ischemic stroke who achieved successful macroscopic endovascular reperfusion, adjunctive tirofiban significantly improved the likelihood of functional independence at 90 days...

2026

CENTAUR

AMX0035 slowed functional decline modestly vs placebo in ALS; later withdrawn after PHOENIX failed.

2020

CHANCE

Clopidogrel plus aspirin for 21 days reduced 90-day stroke vs aspirin alone in minor stroke/TIA in China.

2013

CLARITY

Oral cladribine reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.

2010

CLARITY-AD

Lecanemab anti-amyloid antibody slowed clinical decline in early Alzheimer's disease over 18 months.

2022

CREST-H

In a substudy of the CREST-2 trial, carotid revascularization did not improve cognitive dysfunction over 1 year compared to intensive medical management alone in patients with asymptomatic high-gra...

2026

CRYSTAL-AF

Insertable cardiac monitor detected AF in cryptogenic stroke patients more often than conventional monitoring.

2014

DAWN

Thrombectomy 6-24 hours from last-known-normal with imaging mismatch — substantial functional benefit.

2017

DEFUSE-2

Perfusion-DWI mismatch identified stroke patients more likely to benefit from endovascular reperfusion.

2012

DEFUSE-3

Thrombectomy 6-16 hours in large-vessel occlusion with perfusion mismatch — major outcome improvement.

2018

ECASS-3

IV alteplase between 3 and 4.5 hours improved functional outcomes in acute ischemic stroke vs placebo.

2008

EMERGE/ENGAGE

EMERGE/ENGAGE Phase 3 trials of aducanumab in early Alzheimer's gave mixed results; FDA approved controversially.

2022

ENCHANTED

Low-dose alteplase did not show non-inferiority but reduced symptomatic hemorrhage vs standard dose.

2016

ESCAPE

Rapid endovascular thrombectomy with collaterals selection reduced disability in proximal anterior stroke.

2015

EVOLVE-1

Galcanezumab (anti-CGRP antibody) reduced monthly migraine headache days vs placebo in episodic migraine prevention.

2018

EXTEND

IV alteplase 4.5-9 hours with perfusion imaging selection — improved functional outcomes.

2019

EXTEND-IA

Thrombectomy after IV tPA in patients with perfusion mismatch improved reperfusion and functional outcomes.

2015

FREEDOMS

Oral fingolimod reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.

2010

Frexalimab

In a phase 2 clinical trial, frexalimab, an Fc-engineered anti-CD40L monoclonal antibody, significantly reduced the number of new gadolinium-enhancing brain lesions in patients with relapsing multipl…

2024

INTERACT2

Intensive systolic BP lowering (target <140 mmHg) in acute ICH trended toward better functional outcomes.

2013

IST-3

IV alteplase up to 6 hours did not significantly improve primary outcome but suggested benefit in selected patients.

2012

MCI-186 Study 19

MCI-186-19: IV edaravone slowed functional decline in early-stage ALS with preserved respiratory function.

2017

MR CLEAN

Endovascular thrombectomy within 6 hours improved functional outcomes in proximal anterior circulation stroke.

2015

NINDS

IV alteplase within 3 hours of stroke onset — established acute thrombolysis as standard of care.

1995

OPERA I/II

Ocrelizumab reduced annualized relapse rate vs interferon beta-1a in relapsing-remitting multiple sclerosis.

2017

ORATORIO

Ocrelizumab slowed disability progression vs placebo in primary progressive multiple sclerosis.

2017

POINT

Clopidogrel plus aspirin reduced ischemic events vs aspirin alone after minor stroke or high-risk TIA.

2018

PROMISE-2

IV eptinezumab reduced monthly migraine days vs placebo in chronic migraine prevention.

2020

RESILIENT

Mechanical thrombectomy improved functional outcomes vs medical therapy alone in middle-income country setting.

2020

REVASCAT

Mechanical thrombectomy up to 8 hours improved functional outcomes in proximal anterior circulation occlusion.

2015

SANAD I

SANAD I: lamotrigine had better outcomes than carbamazepine for partial-onset seizures; valproate best for generalized.

2007

SOCRATES

Ticagrelor was not superior to aspirin for prevention of recurrent vascular events after acute ischemic stroke.

2016

SPS3

Dual antiplatelet therapy after lacunar stroke increased bleeding without reducing recurrent stroke.

2012

STRIVE

Erenumab CGRP receptor antagonist reduced monthly migraine days vs placebo in episodic migraine prevention.

2017

SUNBEAM

Ozanimod (S1P modulator) reduced relapse rate vs interferon beta-1a in relapsing-remitting MS.

2019

SWIFT-PRIME

Stent retriever thrombectomy with IV tPA improved functional outcomes vs tPA alone in proximal anterior stroke.

2015

THALES

Ticagrelor plus aspirin reduced stroke/death vs aspirin alone after minor stroke or high-risk TIA.

2020

THRACE

Mechanical thrombectomy after IV tPA improved 3-month functional outcomes in large vessel occlusion stroke.

2016

TIMELESS

Tenecteplase in 4.5-24h window with perfusion mismatch did not improve functional outcomes vs placebo.

2024

TRAILBLAZER-ALZ 2

Donanemab slowed cognitive and functional decline in early symptomatic Alzheimer's with amyloid pathology.

2023

VALOR

Tofersen did not significantly improve ALSFRS-R in SOD1 ALS but lowered neurofilament; conditional FDA approval.

2022

WAKE-UP

IV alteplase in wake-up stroke with DWI-FLAIR mismatch — extended thrombolysis to unknown-onset stroke.

2018

Pulmonology

29 trials

AMBITION

Initial combination ambrisentan plus tadalafil reduced clinical failure vs monotherapy in treatment-naive PAH.

2015

ASCEND

Pirfenidone in IPF (confirmatory trial) — slowed decline, reduced mortality.

2014

BOREAS

Dupilumab reduced exacerbations and improved lung function in COPD with type 2 inflammation (elevated eosinophils).

2023

CAPACITY

Pirfenidone in idiopathic pulmonary fibrosis — slowed lung function decline.

2011

CHEST-1

Riociguat improved exercise capacity and hemodynamics in inoperable CTEPH or persistent PH after PEA.

2013

DREAM

Mepolizumab anti-IL-5 reduced eosinophilic asthma exacerbations vs placebo in severe disease.

2012

ETHOS

Budesonide/glycopyrrolate/formoterol triple therapy reduced exacerbations and all-cause mortality vs dual LAMA/LABA in COPD.

2020

FLAME

LABA/LAMA reduced COPD exacerbations vs ICS/LABA in patients with history of exacerbations.

2016

GRIPHON

Selexipag oral prostacyclin receptor agonist reduced morbidity/mortality events in pulmonary arterial hypertension.

2015

IMPACT

Fluticasone/umeclidinium/vilanterol triple therapy reduced exacerbations vs dual therapy in symptomatic COPD.

2018

INBUILD

Nintedanib slowed FVC decline in progressive fibrosing non-IPF interstitial lung diseases.

2019

INPULSIS-1

Nintedanib in IPF — slowed FVC decline.

2014

INPULSIS-2

Nintedanib slowed annual FVC decline in idiopathic pulmonary fibrosis with manageable side effects.

2014

MENSA

Mepolizumab reduced clinically significant asthma exacerbations in patients with severe eosinophilic asthma.

2014

NAVIGATOR

Tezepelumab anti-TSLP reduced annualized asthma exacerbations vs placebo in severe uncontrolled asthma regardless of phenotype.

2021

NOTUS

NOTUS confirmed dupilumab reduced exacerbations in COPD with type 2 inflammation, supporting FDA approval.

2024

ORBEX

In a randomized trial of high-risk preschool children, prophylactic oral administration of the bacterial lysate OM-85 for 24 months did not significantly reduce the time to first wheezing lower res...

2026

PATENT-1

Riociguat soluble guanylate cyclase stimulator improved exercise capacity and clinical outcomes in PAH.

2013

POET-COPD

Tiotropium reduced time to first moderate-severe COPD exacerbation vs salmeterol over 1 year.

2011

QUEST

Dupilumab reduced exacerbations and improved FEV1 in moderate-severe uncontrolled asthma, especially eosinophilic.

2018

SENSCIS

Nintedanib slowed FVC decline in systemic sclerosis-associated interstitial lung disease over 52 weeks.

2019

SERAPHIN

Macitentan reduced morbidity/mortality composite vs placebo in pulmonary arterial hypertension.

2013

SIRIUS

Mepolizumab reduced oral corticosteroid dose while maintaining asthma control in severe eosinophilic asthma.

2014

STELLAR

Sotatercept added to background therapy improved 6-minute walk distance in pulmonary arterial hypertension.

2023

TORCH

Salmeterol/fluticasone combination did not significantly reduce all-cause mortality vs placebo in moderate-severe COPD.

2007

TRAVERSE

Long-term dupilumab maintained efficacy and safety in patients with moderate-severe asthma over 96 weeks.

2022

TRIBUTE

Single-inhaler triple therapy reduced moderate-severe exacerbations vs LAMA/LABA in symptomatic COPD with prior exacerbations.

2018

UPLIFT

Tiotropium did not slow FEV1 decline but improved lung function and quality of life over 4 years in COPD.

2008

WISDOM

Stepwise withdrawal of ICS in severe COPD did not increase exacerbations but slightly worsened lung function.

2014

Critical Care

37 trials

65 trial

Permissive hypotension (MAP 60-65) did not significantly reduce 90-day mortality vs usual care in older sepsis patients.

2020

6S

Hydroxyethyl starch 130/0.42 increased death and renal replacement therapy vs Ringer's acetate in severe sepsis.

2012

ADRENAL

Continuous infusion hydrocortisone did not reduce 90-day mortality vs placebo in septic shock requiring vasopressors.

2018

ANDROMEDA-SHOCK

Capillary refill vs lactate-guided resuscitation in septic shock — trend toward lower mortality with CRT-guided care.

2019

APROCCHSS

Hydrocortisone plus fludrocortisone reduced 90-day mortality in septic shock with high severity scores.

2018

ARISE

Early goal-directed therapy did not reduce 90-day mortality vs usual care in septic shock.

2014

ARMA (ARDSNet)

Low tidal volume ventilation (6 mL/kg) in ARDS — reduced mortality; defined modern ventilator strategy.

2000

ART

Lung recruitment maneuver and titrated PEEP increased mortality vs low-PEEP strategy in moderate-severe ARDS.

2017

ASTARTÉ

In patients with bacteremia caused by third-generation cephalosporin-resistant Enterobacterales, targeted therapy with intravenous temocillin was non-inferior to carbapenems for 28-day clinical suc...

2026

BaSICS

Balanced solution did not significantly reduce 90-day mortality vs saline in heterogeneous Brazilian ICU patients.

2021

CESAR

ECMO referral in severe respiratory failure — improved 6-month outcomes.

2009

CHEST

Hydroxyethyl starch 130/0.4 increased renal replacement therapy vs saline in critically ill adults.

2012

CORTICUS

Hydrocortisone did not improve survival vs placebo in septic shock regardless of corticotropin test response.

2008

CRASH-2

Early IV tranexamic acid reduced all-cause and bleeding-related mortality in adult trauma patients with hemorrhage.

2010

CRASH-3

Tranexamic acid reduced head-injury-related death in patients with mild/moderate TBI treated early.

2019

EOLIA

Early VV-ECMO did not significantly reduce 60-day mortality vs conventional care in very severe ARDS.

2018

EPaNIC

Late initiation of parenteral nutrition was superior to early in adult ICU patients; less infection and faster recovery.

2011

NICE-SUGAR

Intensive glucose control (81-108 mg/dL) increased mortality vs conventional (<180 mg/dL) in adult ICU patients.

2009

PARAMEDIC2

In adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival and Return of Spontaneous Circulation (ROSC) than placebo, but did not…

2018

PEPTIC

Pantoprazole did not significantly reduce 90-day mortality vs histamine-2 blocker in ICU patients receiving mechanical ventilation.

2020

PLUS

Balanced multielectrolyte solution did not significantly reduce 90-day mortality vs saline in critically ill adults.

2022

ProCESS

Protocolized early goal-directed therapy in sepsis — no mortality benefit vs usual care.

2014

ProMISe

EGDT did not reduce 90-day mortality vs usual resuscitation in early septic shock in UK NHS hospitals.

2015

PROSEVA

Early prolonged prone positioning reduced 28-day mortality in severe ARDS (PaO2/FiO2 <150).

2013

RATE (ECLS)

The RATE trial demonstrated that in adults undergoing ECMO, low-dose unfractionated heparin and therapeutic low-molecular-weight heparin were non-inferior to standard-dose unfractionated heparin fo...

2026

RESHAP-ED

Primary-contact, physiotherapist-led care for uncomplicated musculoskeletal conditions in the emergency department significantly reduces length of stay and improves patient flow without compromisin...

2026

ROSE

Routine early cisatracurium did not reduce 90-day mortality vs usual care with lighter sedation in moderate-severe ARDS.

2019

SAFE

4% albumin and 0.9% saline produced similar 28-day mortality in heterogeneous ICU population.

2004

SALT-ED

Balanced crystalloids reduced major adverse kidney events vs saline in non-critically ill ED patients.

2018

SNAP

In the largest randomized adaptive platform trial for Staphylococcus aureus bacteremia, cefazolin was found to be noninferior to standard antistaphylococcal penicillins for 90-day mortality while sig…

2026

SNAP (PSSA)

The SNAP trial demonstrated that benzylpenicillin halved the risk of acute kidney injury and showed a high probability of non-inferiority for mortality compared to flucloxacillin or cloxacillin in ...

2026

SOAP-II

Norepinephrine reduced arrhythmias vs dopamine in shock; mortality similar overall but dopamine worse in cardiogenic shock.

2010

SUP-ICU

Pantoprazole did not significantly reduce 90-day mortality vs placebo in adult ICU patients at risk for GI bleeding.

2018

TARGET

Energy-dense (1.5 kcal/mL) enteral nutrition did not improve 90-day mortality vs routine in mechanically ventilated adults.

2018

TRICC

Restrictive RBC transfusion (Hgb 7) was non-inferior or superior to liberal (Hgb 10) in critically ill adults.

1999

TRISS

Restrictive transfusion threshold (Hgb 7) similar mortality to liberal (Hgb 9) in septic shock patients.

2014

VASST

Adding vasopressin to norepinephrine did not reduce mortality vs norepinephrine alone in septic shock.

2008

Oncology

139 trials

A166

In a phase III trial of patients with pretreated HER2-positive advanced breast cancer, the novel antibody-drug conjugate trastuzumab botidotin significantly prolonged progression-free survival and ...

2026

AAML1831

PURPOSE The Children's Oncology Group phase III clinical trial AAML1831 (ClinicalTrials.gov identifier: NCT04293562 ) evaluated liposomal daunorubicin and cytarabine (CPX-351) versus standard daunorub

2026

ABBV-011

In a first-in-human phase 1 trial, the SEZ6-targeting antibody-drug conjugate ABBV-011 demonstrated a manageable safety profile and encouraging preliminary antitumor activity, yielding a 25% objectiv…

2024

ACHIEVE-2

The ACHIEVE-2 trial demonstrated that 3 months of oxaliplatin-based adjuvant chemotherapy, particularly CAPOX, provided comparable disease-free survival to the standard 6-month regimen for high-risk…

2020

ACT-GI

PURPOSE Chemotherapy-induced thrombocytopenia (CIT) is a challenging and common complication of cytotoxic chemotherapy in patients with GI cancers.

2026

ADAURA

Adjuvant osimertinib in resected EGFR-mutant NSCLC showed major DFS benefit; established adjuvant TKI standard.

2020

AEGEAN

In patients with resectable non-small-cell lung cancer, perioperative treatment consisting of neoadjuvant durvalumab plus chemotherapy followed by adjuvant durvalumab monotherapy significantly improv…

2023

ALCYONE

Daratumumab plus VMP improved PFS in transplant-ineligible newly diagnosed multiple myeloma.

2018

ALEX

Alectinib improved PFS vs crizotinib as first-line therapy in advanced ALK-positive NSCLC.

2017

ALTA-1L

ALTA-1L showed brigatinib improved PFS vs crizotinib in untreated advanced ALK-positive NSCLC.

2020

APHINITY

Adjuvant pertuzumab + trastuzumab + chemo in HER2+ early breast cancer — modest invasive DFS benefit.

2017

ARASENS

Darolutamide added to ADT plus docetaxel improved OS in metastatic hormone-sensitive prostate cancer.

2022

ASCENT

Sacituzumab govitecan improved OS vs chemo in pretreated metastatic triple-negative breast cancer.

2021

ASCOT

The 5-year final analysis of the phase III ASCOT trial confirms that adjuvant S-1 significantly and sustainably improves overall and relapse-free survival compared to observation in patients with c...

2026

ASPEN-06

In a phase 2 trial of patients with pretreated HER2-overexpressing advanced gastric or gastroesophageal junction cancer, the addition of the CD47 inhibitor evorpacept to trastuzumab, ramucirumab, a...

2026

ATTRACTION-2

In patients with heavily pretreated advanced gastric or gastroesophageal junction cancer, third-line or later treatment with the PD-1 inhibitor nivolumab significantly improved overall survival compa…

2017

AURA3

Osimertinib improved PFS vs chemo in T790M-positive EGFR NSCLC after first-line TKI failure.

2017

BART

PURPOSE To report the primary analysis of a multicenter, phase III randomized trial of adjuvant radiotherapy (RT) after chemotherapy and radical cystectomy (RC) in patients with high-risk muscle-invas

2026

BL-B01D1

The first-in-class EGFR-HER3 bispecific antibody-drug conjugate BL-B01D1 demonstrated promising preliminary antitumor activity and a manageable, predominantly hematologic safety profile in heavily pr…

2024

BRUIN

The phase 1/2 BRUIN trial demonstrated that pirtobrutinib, a highly selective noncovalent BTK inhibitor, is safe and highly active in heavily pretreated B-cell malignancies, overcoming acquired resis…

2021

BRUIN CLL-322

In the phase 3 BRUIN CLL-322 trial, adding the noncovalent BTK inhibitor pirtobrutinib to standard fixed-duration venetoclax-rituximab significantly improved progression-free survival in patients w...

2026

CALGB 80405

Cetuximab and bevacizumab plus chemo showed similar OS in first-line KRAS wild-type metastatic colorectal cancer.

2017

CARTITUDE-1

Cilta-cel BCMA CAR-T produced high response rates and durable remissions in heavily pretreated myeloma.

2021

CARTITUDE-4

Cilta-cel improved PFS vs standard care in lenalidomide-refractory multiple myeloma after 1-3 lines.

2023

CASTOR

Daratumumab added to bortezomib/dex improved PFS in relapsed or refractory multiple myeloma.

2016

CheckMate-067

Nivolumab + ipilimumab or nivolumab alone vs ipilimumab in untreated advanced melanoma — longer progression-free survival; OS data immature.

2015

CheckMate-067

Nivolumab plus ipilimumab improved OS vs ipilimumab alone in untreated advanced melanoma; landmark combo immunotherapy.

2017

CheckMate-214

Nivolumab plus ipilimumab improved OS vs sunitinib in intermediate/poor-risk advanced renal cell carcinoma.

2018

CheckMate-577

Adjuvant nivolumab doubled disease-free survival in resected esophageal/GEJ cancer with residual disease.

2021

CheckMate-649

Nivolumab plus chemo improved OS vs chemo alone in advanced HER2-negative gastric/GEJ adenocarcinoma.

2021

CheckMate-816

Neoadjuvant nivolumab plus chemo before resection in NSCLC improved pCR and event-free survival.

2022

CHOP

The SWOG 8516 trial demonstrated that third-generation intensive chemotherapy regimens were neither more effective nor less toxic than the standard CHOP regimen for advanced non-Hodgkin's lymphoma.

1993

CLEAR

Lenvatinib plus pembrolizumab improved PFS and OS vs sunitinib in advanced renal cell carcinoma.

2021

CLEOPATRA

Pertuzumab + trastuzumab + docetaxel in first-line HER2+ metastatic breast cancer — longer PFS; the survival benefit was reported in 2015.

2012

CodeBreaK 100

Sotorasib showed clinical activity in KRAS G12C-mutated advanced NSCLC, first KRAS-targeted approval.

2021

COMBI-AD

Adjuvant dabrafenib plus trametinib improved relapse-free survival in BRAF-mutant resected stage III melanoma.

2017

COMMIT

PURPOSE Immunotherapy for frontline mismatch repair–deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC) is effective;

2026

COMPETE

[177Lu]Lu-edotreotide versus everolimus for gastroenteropancreatic neuroendocrine tumours (COMPETE): a phase 3, multicentre, randomised, open-label, superiority trial

2026

CROSS

Neoadjuvant chemoradiation improved OS vs surgery alone in resectable esophageal cancer.

2012

CROWN

Lorlatinib improved PFS vs crizotinib in previously untreated advanced ALK-positive NSCLC.

2020

CUPISCO

In patients with unfavorable cancer of unknown primary who achieved disease control after induction chemotherapy, comprehensive genomic profiling followed by molecularly guided therapy significantly…

2024

DART

PURPOSE Concurrent platinum-based chemotherapy and radiation therapy (cCRT) followed by consolidative durvalumab is the standard of care (SoC) for fit patients with inoperable, locally advanced non–sm

2026

DESTINY-Breast03

Trastuzumab deruxtecan vs T-DM1 in HER2+ metastatic breast cancer showed dramatic PFS and OS benefit.

2022

DESTINY-Breast04

T-DXd improved OS in HER2-low metastatic breast cancer, establishing HER2-low as a treatable category.

2022

EAQ171CD

A multicenter randomized controlled trial demonstrating that a virtual sustained tobacco treatment program consisting of telehealth counseling and nicotine replacement therapy significantly increas...

2026

ECHELON-1

Brentuximab vedotin plus AVD improved PFS over ABVD in previously untreated stage III/IV Hodgkin lymphoma.

2018

EMBRACA

Talazoparib (PARP inhibitor) in BRCA+ metastatic breast cancer — improved PFS vs chemotherapy.

2018

EMILIA

T-DM1 improved PFS and OS vs lapatinib/capecitabine in HER2+ advanced breast cancer pretreated.

2012

eNRGy

In the phase 2 eNRGy trial, zenocutuzumab, a bispecific antibody targeting HER2 and HER3, demonstrated a 30% overall response rate with durable anti-tumor activity and a highly favorable safety profi…

2025

EORTC 22033

The mature 13-year follow-up of a phase III trial in high-risk low-grade glioma found no significant overall survival difference between initial temozolomide and standard radiotherapy, reinforcing ...

2026

EPCORE NHL-1

Epcoritamab CD20-CD3 bispecific induced durable responses in relapsed/refractory large B-cell lymphoma.

2023

Euro-EWING99

A large randomized non-inferiority trial demonstrating that cyclophosphamide is non-inferior to ifosfamide as consolidation therapy for standard-risk localized Ewing sarcoma, offering a more favorabl…

2014

EV-302

Enfortumab vedotin plus pembrolizumab improved OS and PFS vs chemo in untreated advanced urothelial carcinoma.

2023

FIND

PURPOSE We hypothesized that a dynamic surveillance strategy guided by circulating tumor DNA (ctDNA) methylation would increase the rate of curative-intent therapy for recurrence in patients with nonm

2026

FLAURA

First-line osimertinib vs first-generation EGFR-TKIs in EGFR-mutant NSCLC — longer PFS (18.9 vs 10.2 months); OS immature at this analysis.

2017

FLAURA2

Osimertinib plus chemo improved PFS vs osimertinib alone in untreated EGFR-mutated advanced NSCLC.

2023

frontMIND

The addition of tafasitamab and lenalidomide to standard R-CHOP therapy significantly prolonged progression-free survival in patients with previously untreated, high-risk diffuse large B-cell lymph...

2026

GMMG-HD7

Mass spectrometry (MS) offers a minimally invasive approach for detecting monoclonal proteins in multiple myeloma (MM), but large prospective evaluations remain limited.

2026

HER2CLIMB

Tucatinib added to trastuzumab/capecitabine in HER2+ metastatic breast cancer improved OS, including brain metastases.

2020

IDEA

IDEA pooled analysis suggested 3 months of adjuvant CAPOX non-inferior to 6 months in low-risk stage III colon cancer.

2018

IMbrave150

Atezolizumab plus bevacizumab improved OS and PFS vs sorafenib in unresectable hepatocellular carcinoma.

2020

IMpassion130

Atezolizumab + nab-paclitaxel in PD-L1+ TNBC — PFS benefit (controversial OS).

2018

IMpower010

Adjuvant atezolizumab after resection in stage II-IIIA NSCLC improved DFS in PD-L1 positive disease.

2021

JCOG1008

In patients with postoperative high-risk locally advanced head and neck squamous cell carcinoma, chemoradiotherapy with weekly cisplatin was noninferior to standard 3-weekly cisplatin for overall sur…

2022

KarMMa

Ide-cel BCMA CAR-T showed deep responses in heavily pretreated relapsed/refractory multiple myeloma.

2021

KATHERINE

T-DM1 vs trastuzumab in residual HER2+ breast cancer after neoadjuvant therapy — major iDFS benefit.

2019

KEYNOTE-024

First-line pembrolizumab vs chemotherapy in PD-L1-high NSCLC — major overall survival benefit.

2016

KEYNOTE-054

Adjuvant pembrolizumab improved recurrence-free survival in resected high-risk stage III melanoma.

2018

KEYNOTE-189

First-line pembrolizumab + chemo in non-squamous NSCLC — significant OS and PFS gain.

2018

KEYNOTE-407

First-line pembrolizumab + chemo in squamous NSCLC — improved overall survival.

2018

KEYNOTE-426

Pembrolizumab plus axitinib improved OS and PFS vs sunitinib in advanced renal cell carcinoma.

2019

KEYNOTE-522

Neoadjuvant pembrolizumab plus chemo in early triple-negative breast cancer improved pCR and event-free survival.

2020

KEYNOTE-590

Pembrolizumab plus chemo improved OS in advanced esophageal and esophagogastric junction cancer.

2021

KEYNOTE-826

Pembrolizumab plus chemo improved OS in persistent, recurrent, or metastatic cervical cancer.

2021

KRYSTAL-1

Adagrasib produced a 42.9% response rate in previously treated KRAS G12C-mutated NSCLC, with intracranial activity.

2022

LATITUDE

Abiraterone plus prednisone added to ADT improved OS in newly diagnosed high-risk metastatic hormone-sensitive prostate cancer.

2017

LITESPARK-011

Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial

2026

MAGIC

Perioperative ECF chemotherapy improved OS vs surgery alone in resectable gastric/lower esophageal cancer.

2006

MAGNITUDE

Niraparib plus abiraterone improved PFS in HRR-positive metastatic castration-resistant prostate cancer.

2022

MAIA

Daratumumab plus Rd improved PFS and depth of response in transplant-ineligible newly diagnosed myeloma; OS immature at this report.

2019

MajesTEC-1

Teclistamab BCMA-CD3 bispecific produced durable responses in heavily pretreated relapsed/refractory myeloma.

2022

MARIPOSA

Amivantamab plus lazertinib improved PFS vs osimertinib in first-line EGFR-mutated advanced NSCLC.

2023

MATTERHORN

In patients with resectable gastric or gastroesophageal junction adenocarcinoma, the addition of perioperative durvalumab to standard FLOT chemotherapy significantly improved event-free survival comp…

2025

MINDACT

MammaPrint genomic test identified breast cancer patients who could safely skip adjuvant chemotherapy.

2016

MONALEESA-2

Ribociclib plus letrozole prolonged PFS in postmenopausal HR+/HER2- advanced breast cancer; OS benefit was reported in 2022.

2016

monarchE

Adjuvant abemaciclib plus endocrine therapy in high-risk HR+/HER2- early breast cancer improved invasive DFS.

2020

MOSAIC

Adjuvant FOLFOX improved DFS over 5-FU/LV in resected stage II/III colon cancer; established standard.

2004

NAPOLI-3

NALIRIFOX improved OS vs gem/nab-paclitaxel in untreated metastatic pancreatic adenocarcinoma.

2023

NEMIO

PURPOSE To evaluate the efficacy and safety of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) combined with durvalumab ± tremelimumab in patients with muscle-inv

2026

neoCARHP

The neoCARHP trial investigators clarify their creatinine assay and carboplatin dosing methodology, affirming that the higher rate of hematologic toxicity in the carboplatin arm was due to expected...

2026

NETTER-1

177Lu-DOTATATE PRRT in advanced midgut neuroendocrine tumors — established peptide receptor radionuclide therapy.

2017

NOAH

Neoadjuvant trastuzumab plus chemo improved event-free survival in HER2+ locally advanced breast cancer.

2010

NOVA

Niraparib maintenance improved PFS in platinum-sensitive recurrent ovarian cancer, regardless of BRCA status.

2016

OlympiA

One year of adjuvant olaparib improved invasive DFS in BRCA-mutated high-risk early breast cancer.

2021

PACIFIC

Durvalumab consolidation after chemoradiation in unresectable stage III NSCLC — markedly longer PFS; OS reported later.

2017

PACIFIC-2

Concurrent durvalumab with chemoradiation in unresectable stage III NSCLC did not improve PFS vs sequential.

2024

PALOMA-2

Palbociclib plus letrozole improved PFS in postmenopausal HR+/HER2- metastatic breast cancer first-line.

2016

PALOMA-3

Palbociclib plus fulvestrant improved PFS in pretreated HR+/HER2- advanced breast cancer.

2015

PAOLA-1

Olaparib plus bevacizumab maintenance improved PFS in advanced ovarian cancer, especially HRD-positive.

2019

PATHFINDER

A prospective cohort study demonstrating the clinical feasibility of using a blood-based multi-cancer early detection (MCED) test to screen for multiple cancers simultaneously and direct subsequent d…

2023

PCDC

An international prospective biomarker study developed and validated PANXEON, a liquid biopsy assay combining a 10-miRNA signature with CA 19-9, demonstrating high sensitivity for detecting early-s...

2026

PIVOTAL

In patients with resectable stage III melanoma, neoadjuvant intralesional administration of daromun (L19IL2 and L19TNF) prior to surgery significantly prolonged recurrence-free and distant metastasis…

2025

POLARIX

Pola-R-CHP improved PFS vs R-CHOP in previously untreated intermediate/high-risk DLBCL.

2022

POSEIDON

Tremelimumab plus durvalumab plus chemo improved OS vs chemo alone in untreated metastatic NSCLC.

2022

PRADA

In women receiving adjuvant anthracycline-containing therapy for early breast cancer, concomitant treatment with the angiotensin receptor blocker candesartan protected against early decline in left v…

2016

PRIMA

Niraparib maintenance improved PFS in newly diagnosed advanced ovarian cancer regardless of BRCA status.

2019

PRODIGE 23

Neoadjuvant FOLFIRINOX before chemoradiation improved DFS in locally advanced rectal cancer.

2021

PROfound

Olaparib improved PFS and OS vs enzalutamide/abi in HRR-mutated metastatic castration-resistant prostate cancer.

2020

RADICAL

PURPOSE Bone metastases (BM) occur in approximately 30% of patients with metastatic renal cell carcinoma (mRCC) and are associated with poor survival and symptomatic skeletal events (SSEs).

2026

RAPIDO

Short-course RT followed by chemo before surgery reduced disease-related treatment failure in rectal cancer.

2020

RCTS

PURPOSE Clinical data for first-line combination of antibody-drug conjugates (ADC) and immune checkpoint inhibitors in human epidermal growth factor receptor 2 (HER2)–overexpressing advanced gastric o

2026

REIMAGINE

In a prospective community-based screening study, upfront biparametric MRI detected a substantial number of clinically significant prostate cancers in men with normal PSA levels, demonstrating the fe…

2023

RELATIVITY-047

Relatlimab plus nivolumab (LAG-3 + PD-1) improved PFS vs nivolumab alone in untreated advanced melanoma.

2022

RELIGHT

The phase III RELIGHT trial demonstrated that adding the novel anti-PD-L1/TGF-β bispecific antibody retlirafusp alfa to first-line CAPOX chemotherapy significantly improved overall survival and pro...

2026

ROAM/EORTC-1308

In patients with completely resected WHO grade 2 atypical meningioma, early adjuvant radiotherapy significantly reduces the risk of tumor recurrence and improves 5-year disease-free survival compar...

2026

RUBY

Dostarlimab plus chemo improved PFS in advanced endometrial cancer, especially dMMR/MSI-H tumors.

2023

RxPONDER

Postmenopausal women with HR+ node-positive breast cancer and low recurrence score could omit chemotherapy.

2021

SHARE

PURPOSE To compare hypofractionated radiotherapy (RT) with conventional RT for treating biochemical recurrence following radical prostatectomy.

2026

SOLO-1

Olaparib maintenance dramatically improved PFS in newly diagnosed BRCA-mutated advanced ovarian cancer.

2018

STAMPEDE (docetaxel)

STAMPEDE: adding docetaxel to first-line hormone therapy improved survival in advanced prostate cancer; zoledronic acid did not.

2016

STELLAR

In patients with locally advanced rectal cancer, short-term radiotherapy followed by neoadjuvant chemotherapy (total neoadjuvant therapy) was non-inferior to standard long-term chemoradiotherapy for…

2022

SU2C-SARC032

Tumor-informed personalized ctDNA profiling successfully detected baseline circulating tumor DNA in 85% of patients with localized soft tissue sarcomas and provided independent prognostic informati...

2026

SUCCESSOR-2

Mezigdomide, carfilzomib, and dexamethasone versus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma (SUCCESSOR-2): a phase 3, open-label, randomised controlled tr

2026

SWOG 8794

In men with pathologically advanced prostate cancer following radical prostatectomy, adjuvant radiotherapy significantly reduces the risk of PSA relapse and disease recurrence, with a trend toward im…

2006

SWOG/NRG S1914

The phase 3 SWOG/NRG S1914 trial demonstrated that adding the immune checkpoint inhibitor atezolizumab to stereotactic body radiation therapy (SBRT) in high-risk, early-stage, medically inoperable ...

2026

TAILORx

Endocrine therapy alone non-inferior to chemo-endocrine in HR+/HER2- node-negative breast cancer with mid-range RS.

2018

TITAN

Apalutamide added to ADT improved OS and radiographic PFS in metastatic castration-sensitive prostate cancer.

2019

TOPAZ-1

Durvalumab plus chemo improved OS vs chemo alone in advanced biliary tract cancer first-line.

2022

TOURMALINE-MM1

Ixazomib added to Rd improved PFS in relapsed/refractory multiple myeloma.

2016

Trastuzumab

The addition of the anti-HER2 monoclonal antibody trastuzumab to standard chemotherapy significantly improved time to progression and overall survival in women with HER2-overexpressing metastatic bre…

2001

TRAVERSE

PURPOSE Treatment options for clear cell renal cell carcinoma (ccRCC) refractory to immune checkpoint inhibitors (ICIs) and targeted therapy are needed.

2026

TRIANGLE

In younger patients with mantle cell lymphoma, adding ibrutinib to frontline induction and maintenance significantly improved failure-free survival, and standard ASCT was not superior to an ibrutinib…

2024

TROPiCS-02

Sacituzumab govitecan improved PFS vs chemotherapy in pretreated HR+/HER2- metastatic breast cancer; OS not yet mature in this report.

2022

TROPION-Lung01

Dato-DXd improved PFS modestly vs docetaxel in previously treated advanced NSCLC, especially nonsquamous.

2023

TXI

In an international, multicenter randomized trial, the use of Texture and Color Enhancement Imaging (TXI) during colonoscopy significantly increased the adenoma detection rate compared to standard hi…

2023

WSG TP-II

The WSG-TP-II trial found that neoadjuvant de-escalated chemotherapy (paclitaxel) combined with dual HER2 blockade achieved a significantly higher pathological complete response rate than endocrine t…

2023

X-ACT

Adjuvant capecitabine non-inferior to 5-FU/LV in stage III colon cancer with better tolerability.

2005

ZUMA-1

Axi-cel CAR-T showed durable responses in refractory large B-cell lymphoma, leading to FDA approval.

2017

ZUMA-7

Axi-cel improved event-free survival vs standard care as second-line therapy in relapsed/refractory LBCL.

2022

Infectious Disease

49 trials

ACTIV-3

Bamlanivimab did not improve outcomes in hospitalized adults with COVID-19 and was discontinued for futility.

2021

ACTT-1

Remdesivir in hospitalized COVID-19 — shorter time to recovery; modest mortality signal.

2020

ACTT-2

Baricitinib plus remdesivir shortened recovery time and improved outcomes vs remdesivir in hospitalized COVID-19.

2021

ASTRAL-1

Sofosbuvir-velpatasvir for 12 weeks achieved 99% SVR12 in HCV genotypes 1, 2, 4, 5 and 6 (genotype 3 was ASTRAL-3).

2015

BNT162b2

Pfizer-BioNTech mRNA COVID-19 vaccine Phase 3 — 95% efficacy.

2020

C-EDGE

Elbasvir-grazoprevir achieved high SVR12 rates in chronic HCV genotype 1, 4, 6 treatment-naive patients.

2015

CAPiTA

PCV13 prevented vaccine-type community-acquired pneumococcal pneumonia in adults aged 65+.

2015

ChAdOx1

ChAdOx1 nCoV-19 adenoviral COVID-19 vaccine showed efficacy against symptomatic disease in pooled Phase 3.

2021

COMET-ICE

COMET-ICE: sotrovimab reduced progression to hospitalization or death in high-risk non-hospitalized COVID-19.

2021

COV-BARRIER

Baricitinib reduced 28-day mortality in hospitalized adults with COVID-19 requiring oxygen.

2021

COVACTA

Tocilizumab in hospitalized severe COVID-19 pneumonia did not improve clinical status at day 28.

2021

DISCOVER

F/TAF non-inferior to F/TDF for HIV PrEP in men and transgender women, with better renal/bone safety.

2020

EMPACTA

Tocilizumab reduced progression to mechanical ventilation or death in hospitalized COVID-19 pneumonia.

2021

ENSEMBLE

Single-dose Ad26.COV2.S vaccine was efficacious against moderate-severe COVID-19 across multiple regions.

2021

EPIC-HR

Nirmatrelvir-ritonavir reduced COVID-19 hospitalization or death by ~89% in high-risk unvaccinated outpatients.

2022

FLU-IVIG

Anti-influenza hyperimmune IV immunoglobulin did not improve outcomes in hospitalized influenza patients.

2019

High-Dose Flu Vaccine (FIM12)

High-dose inactivated influenza vaccine more efficacious than standard dose in adults aged 65 and older.

2014

HPTN-052

Early ART in HIV-positive partner cut HIV transmission to serodiscordant partners by ~96%.

2011

HPTN-083

Injectable cabotegravir every 8 weeks more effective than oral TDF/FTC for HIV PrEP in MSM/TGW.

2021

ION-1

Ledipasvir-sofosbuvir achieved >95% SVR12 in treatment-naive genotype 1 HCV without ribavirin.

2014

iPrEx

Oral TDF/FTC pre-exposure prophylaxis reduced HIV acquisition in men who have sex with men.

2010

MATISSE

Maternal RSVpreF vaccination prevented medically attended severe RSV in infants up to 6 months.

2023

MELODY

Single-dose nirsevimab reduced medically attended RSV lower respiratory illness in healthy infants.

2022

MERINO

Piperacillin-tazobactam inferior to meropenem for ceftriaxone-resistant E. coli/Klebsiella bacteremia mortality.

2018

MOVe-OUT

Molnupiravir reduced hospitalization/death in non-hospitalized adults with mild-moderate COVID-19 at risk.

2022

mRNA-1273

Moderna mRNA COVID-19 vaccine Phase 3 — 94% efficacy.

2020

Nix-TB

BPaL regimen (bedaquiline, pretomanid, linezolid) showed high cure rates in XDR and pretreated MDR-TB.

2020

NVX-CoV2373

Novavax NVX-CoV2373 protein-subunit vaccine showed ~90% efficacy against symptomatic COVID-19 in Phase 3.

2021

OFLOTUB

Gatifloxacin-containing 4-month regimen for drug-susceptible TB was inferior to standard 6-month therapy.

2014

PANORAMIC

Molnupiravir did not reduce hospitalization/death in vaccinated high-risk outpatients with COVID-19.

2022

PARTNER2

PARTNER2: zero linked HIV transmissions among gay serodifferent couples with a virally suppressed partner across 76,088 condomless sex acts (U=U).

2019

PNEUMOSIL

PNEUMOSIL 10-valent pneumococcal conjugate vaccine was non-inferior to Synflorix (PHiD-CV) for IgG responses in Gambian infants.

2020

PREVENT TB

TBTC Study 26 / PREVENT TB: 12-dose weekly rifapentine-isoniazid (3HP) non-inferior to 9-month isoniazid.

2011

PURPOSE-1

Twice-yearly injectable lenacapavir prevented all HIV infections in cisgender women in sub-Saharan Africa.

2024

PURPOSE-2

Twice-yearly lenacapavir reduced HIV incidence vs daily oral TDF/FTC in MSM and gender-diverse populations.

2024

R21

R21/Matrix-M malaria vaccine showed high efficacy against clinical malaria in African children Phase 3.

2023

RECOVERY

Dexamethasone in hospitalized COVID-19 — first proven mortality-reducing therapy in COVID-19.

2021

REMAP-CAP

Tocilizumab and sarilumab improved organ-support-free days in critically ill COVID-19 patients.

2021

REMoxTB

4-month moxifloxacin-containing regimens failed noninferiority to standard 6-month therapy for drug-sensitive TB — more relapses despite faster culture conversion.

2014

RENOIR

Bivalent RSVpreF vaccine prevented RSV-associated lower respiratory illness in adults aged 60+.

2023

RTS,S

RTS,S/AS01 malaria vaccine provided partial protection against clinical and severe malaria in African children.

2015

SMART

Continuous ART was superior to CD4-guided treatment interruption for opportunistic disease and death.

2006

SOLIDARITY

WHO multi-drug COVID-19 treatment trial — remdesivir, HCQ, lopinavir, and IFN-β not effective on mortality.

2020

START

Immediate ART initiation reduced serious AIDS/non-AIDS events in HIV-positive adults with CD4 above 500.

2015

STIMULATE-ICP

The STIMULATE-ICP phase 3 cluster-randomized trial found that while multidisciplinary specialist care improved fatigue in Long COVID patients, adding multi-organ MRI or digital rehabilitation yield...

2026

STREAM

9-month MDR-TB regimen non-inferior to longer WHO regimen with similar safety, more affordable.

2019

Study 31/A5349

Study 31/A5349: 4-month rifapentine/moxifloxacin regimen non-inferior to standard 6-month therapy for drug-susceptible TB.

2021

TEMPRANO

Early ART and isoniazid prophylaxis reduced severe illness/death in HIV-positive adults in West Africa.

2015

ZOE-50/70

Recombinant adjuvanted zoster vaccine (Shingrix) reduced herpes zoster incidence by ~90% in older adults.

2016

Women’s Health & OB-GYN

21 trials

ALPS

Antenatal betamethasone in late preterm pregnancy reduced respiratory morbidity in newborns vs placebo.

2016

ARRIVE

Elective induction at 39 weeks vs expectant management in low-risk nulliparous women — fewer cesareans without harm.

2018

ASPRE

Low-dose aspirin in high-risk women reduced preterm preeclampsia vs placebo in first-trimester screening cohort.

2017

BEAM

Antenatal magnesium sulfate reduced moderate-severe cerebral palsy in surviving infants born very preterm.

2008

Cerclage (Owen 2009)

Ultrasound-indicated cerclage for cervix <25 mm after prior preterm birth — no significant drop in birth <35 weeks overall; fewer previable births and perinatal deaths.

2009

CHAP

Treating mild chronic hypertension to BP <140/90 reduced adverse pregnancy outcomes without harming fetal growth.

2022

CHIPS

Tight blood pressure control in non-severe pregnancy hypertension did not improve perinatal outcomes vs less tight.

2015

GBS3

GBS3 process-outcomes paper: universal late-pregnancy GBS testing was feasible and acceptable in UK maternity units; this paper does not report clinical effectiveness.

2026

HAPO

HAPO: maternal glucose levels below diabetes thresholds were associated with adverse pregnancy outcomes.

2008

HERS

Estrogen plus progestin did not reduce CHD events in women with established coronary heart disease.

1998

MAGPIE

Magnesium sulfate halved the risk of eclampsia in women with preeclampsia compared with placebo.

2002

Meis 17P

17-OHPC weekly reduced recurrent preterm birth vs placebo in women with prior spontaneous preterm delivery.

2003

MOMS

Prenatal repair of myelomeningocele reduced need for VP shunt and improved motor outcomes vs postnatal repair.

2011

MsFLASH

Escitalopram modestly reduced frequency and severity of menopausal hot flashes vs placebo in non-hormonal trial.

2011

PRISM

Vaginal progesterone did not improve overall live birth rate but benefitted women with prior miscarriages.

2019

PROLONG

PROLONG: 17-OHPC did not reduce recurrent preterm birth in women with prior spontaneous preterm delivery.

2019

SKYLIGHT 1

Fezolinetant NK3 receptor antagonist reduced moderate-severe vasomotor symptoms in menopause vs placebo.

2023

STRIDER

Sildenafil did not improve outcomes in severe early-onset fetal growth restriction and was associated with neonatal harm.

2018

Term Breech

Planned cesarean delivery reduced perinatal mortality/morbidity vs planned vaginal birth for term breech presentation.

2000

WHI (E+P)

Hormone replacement (estrogen + progestin) in postmenopausal women — increased breast cancer and CVD; stopped early.

2002

WOMAN

Tranexamic acid reduced death due to bleeding in women with postpartum hemorrhage when given early.

2017

General Medicine

36 trials

ALLHAT-LLT

Pravastatin did not significantly reduce all-cause mortality vs usual care in hypertensive adults aged 55+.

2002

ASPREE

Low-dose aspirin in healthy elderly primary prevention — no benefit, increased bleeding.

2018

D2d

Vitamin D3 4000 IU daily did not significantly reduce progression to T2D in adults with prediabetes.

2019

DASH

DASH dietary pattern lowered systolic and diastolic blood pressure substantially in adults with high-normal/Stage 1 HTN.

1997

DASH-Sodium

Reducing sodium intake plus DASH diet lowered blood pressure more than either intervention alone.

2001

DCCT

Intensive vs conventional glycemic control in T1DM — major reduction in microvascular complications.

1993

EAGLES

Varenicline and bupropion did not increase neuropsychiatric adverse events vs NRT/placebo in smokers.

2016

FINGER

The FINGER trial demonstrated that a 2-year multidomain lifestyle intervention significantly improves or maintains cognitive functioning in older adults at increased risk for dementia compared to reg…

2015

HOPE

Ramipril reduced CV events in patients with vascular disease or diabetes plus a CV risk factor.

2000

ISLEND-2

Switching virologically suppressed adults with HIV-1 to a once-weekly oral single-tablet regimen of islatravir and lenacapavir is non-inferior to continuing daily standard-of-care antiretroviral th...

2026

LATA

In virologically suppressed adolescents living with HIV in sub-Saharan Africa, switching to long-acting injectable cabotegravir-rilpivirine every 8 weeks was superior to daily oral standard-of-care...

2026

LatAm-FINGERS

The LatAm-FINGERS trial demonstrated that a culturally tailored, 2-year multidomain lifestyle intervention significantly improved global cognition compared to standard health advice in at-risk olde...

2026

MEGA

Pravastatin reduced coronary events in Japanese adults with hypercholesterolemia without prior CVD.

2006

NELSON

Volume CT lung cancer screening reduced lung cancer mortality in male former and current smokers in Europe.

2020

NICUSeq

In acutely ill infants with suspected genetic diseases, early whole-genome sequencing doubled the rate of diagnostic yield and significantly increased actionable changes in clinical management compar…

2021

NLST

NLST: low-dose CT screening reduced lung cancer mortality by 20% vs chest x-ray in high-risk smokers.

2011

NORDICC

Invitation to colonoscopy reduced colorectal cancer risk modestly; effect attenuated by limited uptake.

2022

PLCO

PLCO: organized annual PSA screening showed no prostate-cancer mortality benefit vs usual care at 13 years (RR 1.09, 95% CI 0.87-1.36).

2012

PolyIran

Polypill containing aspirin, statin, and antihypertensives reduced major CV events in Iranian rural cohort.

2019

PREDIMED

Mediterranean diet with olive oil or nuts reduced major CV events vs low-fat diet in high-risk adults.

2013

PREDIMED-Plus

PREDIMED-Plus interim analysis: an intensive energy-reduced Mediterranean diet program improved diet adherence at 12 months vs usual advice; this paper reports no cardiovascular outcomes.

2019

PROSPER

Pravastatin reduced coronary events in older adults at risk for CVD with mixed effects in primary prevention.

2002

PURE

PURE study: high carbohydrate intake associated with higher mortality; total fat with lower mortality globally.

2017

REFIT2

A large phase 3 trial demonstrated that a single administration of faecal microbiota transplantation via rectal enema provided no clinical benefit over an autologous placebo in patients with modera...

2026

SHEP

Antihypertensive drug treatment of isolated systolic hypertension in elderly reduced stroke and CV events.

1991

SPRINT-MIND

Intensive BP control (target <120 mmHg) reduced MCI and combined MCI/dementia but not probable dementia alone.

2019

SSaSS

SSaSS: salt substitute with reduced sodium and added potassium reduced stroke and CV events in rural China.

2021

STAREE

STAREE: atorvastatin 40 mg in adults 70+ without CVD lowered major cardiovascular events (HR 0.70) but did not extend disability-free survival (HR 0.94) over 5.9 years.

2026

TIPS-3

TIPS-3: polypill plus aspirin reduced CV events vs placebo in intermediate-risk adults without CVD.

2021

TONE

Weight loss and sodium reduction reduced need for antihypertensive medication in older adults with HTN.

1998

VITAL

Vitamin D3 2000 IU and omega-3 1g daily did not reduce major CV events or cancer vs placebo over 5 years.

2019

VITAL-Bone

Vitamin D3 2000 IU daily did not reduce fractures in generally healthy older adults without low BMD or vitamin D deficiency.

2022

VITAL-DEP

Vitamin D3 2000 IU daily did not reduce incident depression in older adults without baseline depression.

2020

VITAL-Rhythm

Vitamin D and omega-3 did not reduce incidence of atrial fibrillation in primary prevention population.

2020

WHI Diet

Low-fat dietary pattern did not reduce breast cancer, colorectal cancer, or CHD over 8 years in postmenopausal women.

2006

WHISH

WHISH design and baseline paper: a pragmatic physical-activity trial in 49,331 older women; this paper reports no outcomes.

2021

Other

1 trial

Last 24 hours

4 trials

Last 7 days

2 trials

Last 30 days

47 trials

SU2C-SARC032

Tumor-informed personalized ctDNA profiling successfully detected baseline circulating tumor DNA in 85% of patients with localized soft tissue sarcomas and provided independent prognostic informati...

2026

A166

In a phase III trial of patients with pretreated HER2-positive advanced breast cancer, the novel antibody-drug conjugate trastuzumab botidotin significantly prolonged progression-free survival and ...

2026

LATA

In virologically suppressed adolescents living with HIV in sub-Saharan Africa, switching to long-acting injectable cabotegravir-rilpivirine every 8 weeks was superior to daily oral standard-of-care...

2026

PCDC

An international prospective biomarker study developed and validated PANXEON, a liquid biopsy assay combining a 10-miRNA signature with CA 19-9, demonstrating high sensitivity for detecting early-s...

2026

ORBEX

In a randomized trial of high-risk preschool children, prophylactic oral administration of the bacterial lysate OM-85 for 24 months did not significantly reduce the time to first wheezing lower res...

2026

CREST-H

In a substudy of the CREST-2 trial, carotid revascularization did not improve cognitive dysfunction over 1 year compared to intensive medical management alone in patients with asymptomatic high-gra...

2026

TIMI 11B

Enoxaparin vs unfractionated heparin in non-ST ACS — reduced composite of death, MI, urgent revascularization.

1999

ORBITA

PCI vs sham procedure in stable single-vessel CAD — no significant improvement in exercise time vs sham.

2018

IMbrave150

Atezolizumab plus bevacizumab improved OS and PFS vs sorafenib in unresectable hepatocellular carcinoma.

2020

ADRENAL

Continuous infusion hydrocortisone did not reduce 90-day mortality vs placebo in septic shock requiring vasopressors.

2018

A-HeFT

Hydralazine/isosorbide dinitrate in self-identified Black patients with HFrEF — reduced mortality, stopped early.

2004

LoDoCo2

Low-dose colchicine in chronic coronary disease — reduced major CV events vs placebo.

2020

RxPONDER

Postmenopausal women with HR+ node-positive breast cancer and low recurrence score could omit chemotherapy.

2021

ALTA-1L

ALTA-1L showed brigatinib improved PFS vs crizotinib in untreated advanced ALK-positive NSCLC.

2020

STAREE

STAREE: atorvastatin 40 mg in adults 70+ without CVD lowered major cardiovascular events (HR 0.70) but did not extend disability-free survival (HR 0.94) over 5.9 years.

2026

HOPE

Ramipril reduced CV events in patients with vascular disease or diabetes plus a CV risk factor.

2000

PLCO

PLCO: organized annual PSA screening showed no prostate-cancer mortality benefit vs usual care at 13 years (RR 1.09, 95% CI 0.87-1.36).

2012

AWARD-7

AWARD-7: once-weekly dulaglutide vs insulin glargine in T2D with stage 3-4 CKD — noninferior HbA1c lowering, with higher eGFR at 52 weeks.

2018

NLST

NLST: low-dose CT screening reduced lung cancer mortality by 20% vs chest x-ray in high-risk smokers.

2011

HEART-FID

HEART-FID: IV ferric carboxymaltose vs placebo in HFrEF with iron deficiency — no apparent difference in the hierarchical composite of death, HF hospitalization or 6-minute walk distance.

2023

PROLONG

PROLONG: 17-OHPC did not reduce recurrent preterm birth in women with prior spontaneous preterm delivery.

2019

CheckMate-067

Nivolumab plus ipilimumab improved OS vs ipilimumab alone in untreated advanced melanoma; landmark combo immunotherapy.

2017

MITRA-FR

MitraClip + medical therapy vs medical therapy alone in HF with secondary MR — no benefit (contrast COAPT).

2018

SNAP (PSSA)

The SNAP trial demonstrated that benzylpenicillin halved the risk of acute kidney injury and showed a high probability of non-inferiority for mortality compared to flucloxacillin or cloxacillin in ...

2026

SWOG/NRG S1914

The phase 3 SWOG/NRG S1914 trial demonstrated that adding the immune checkpoint inhibitor atezolizumab to stereotactic body radiation therapy (SBRT) in high-risk, early-stage, medically inoperable ...

2026

LatAm-FINGERS

The LatAm-FINGERS trial demonstrated that a culturally tailored, 2-year multidomain lifestyle intervention significantly improved global cognition compared to standard health advice in at-risk olde...

2026

BRUIN CLL-322

In the phase 3 BRUIN CLL-322 trial, adding the noncovalent BTK inhibitor pirtobrutinib to standard fixed-duration venetoclax-rituximab significantly improved progression-free survival in patients w...

2026

RATE (ECLS)

The RATE trial demonstrated that in adults undergoing ECMO, low-dose unfractionated heparin and therapeutic low-molecular-weight heparin were non-inferior to standard-dose unfractionated heparin fo...

2026

ATTRACTION (stroke)

In patients with acute ischemic stroke who achieved successful macroscopic endovascular reperfusion, adjunctive tirofiban significantly improved the likelihood of functional independence at 90 days...

2026

REIMAGINE 3

In adults with type 2 diabetes inadequately controlled on basal insulin, the addition of the once-weekly dual agonist cagrilintide–semaglutide (CagriSema) yielded profound improvements in glycemic ...

2026

ACHIEVE-2 (orforglipron)

In adults with type 2 diabetes inadequately controlled on metformin, the novel oral non-peptide GLP-1 receptor agonist orforglipron demonstrated superior glycemic control and greater weight loss co...

2026

PHOENYCS GO

The phase 3 PHOENYCS GO trial demonstrated that the novel Fc-free CD40 ligand inhibitor dapirolizumab pegol, added to standard of care, significantly improved disease activity and enabled glucocort...

2026

frontMIND

The addition of tafasitamab and lenalidomide to standard R-CHOP therapy significantly prolonged progression-free survival in patients with previously untreated, high-risk diffuse large B-cell lymph...

2026

RESHAP-ED

Primary-contact, physiotherapist-led care for uncomplicated musculoskeletal conditions in the emergency department significantly reduces length of stay and improves patient flow without compromisin...

2026

RACER-Knee

In patients with advanced knee osteoarthritis, robotic-arm-assisted total knee replacement did not improve joint awareness or functional outcomes at 12 months compared to conventional surgery, whil...

2026

PVI-SHAM-AF

In a sham-controlled trial of patients with symptomatic atrial fibrillation, catheter ablation did not significantly improve AF-related quality of life compared to a sham procedure at 6 months, des...

2026

Kylo-11

In a phase 1 trial, a single dose of the novel long-acting siRNA Kylo-11 was well-tolerated and produced exceptionally deep, durable reductions in lipoprotein(a) of up to 97% over 48 weeks.

2026

ISLEND-2

Switching virologically suppressed adults with HIV-1 to a once-weekly oral single-tablet regimen of islatravir and lenacapavir is non-inferior to continuing daily standard-of-care antiretroviral th...

2026

STIMULATE-ICP

The STIMULATE-ICP phase 3 cluster-randomized trial found that while multidisciplinary specialist care improved fatigue in Long COVID patients, adding multi-organ MRI or digital rehabilitation yield...

2026

MATTERHORN

In patients with resectable gastric or gastroesophageal junction adenocarcinoma, the addition of perioperative durvalumab to standard FLOT chemotherapy significantly improved event-free survival comp…

2025

OPTIMA-AF

In patients with atrial fibrillation undergoing percutaneous coronary intervention, one month of dual antithrombotic therapy followed by DOAC monotherapy was non-inferior to 12 months of dual thera...

2026

EAQ171CD

A multicenter randomized controlled trial demonstrating that a virtual sustained tobacco treatment program consisting of telehealth counseling and nicotine replacement therapy significantly increas...

2026

ASTARTÉ

In patients with bacteremia caused by third-generation cephalosporin-resistant Enterobacterales, targeted therapy with intravenous temocillin was non-inferior to carbapenems for 28-day clinical suc...

2026

EORTC 22033

The mature 13-year follow-up of a phase III trial in high-risk low-grade glioma found no significant overall survival difference between initial temozolomide and standard radiotherapy, reinforcing ...

2026

SWOG 8794

In men with pathologically advanced prostate cancer following radical prostatectomy, adjuvant radiotherapy significantly reduces the risk of PSA relapse and disease recurrence, with a trend toward im…

2006

CUPISCO

In patients with unfavorable cancer of unknown primary who achieved disease control after induction chemotherapy, comprehensive genomic profiling followed by molecularly guided therapy significantly…

2024

AEGEAN

In patients with resectable non-small-cell lung cancer, perioperative treatment consisting of neoadjuvant durvalumab plus chemotherapy followed by adjuvant durvalumab monotherapy significantly improv…

2023

Last year

530 trials

SHARE

PURPOSE To compare hypofractionated radiotherapy (RT) with conventional RT for treating biochemical recurrence following radical prostatectomy.

2026

ITACS

Abstract Objective To evaluate the effects of intravenous iron on red cell transfusion and recovery after cardiac surgery.

2026

PIVOTAL

In patients with resectable stage III melanoma, neoadjuvant intralesional administration of daromun (L19IL2 and L19TNF) prior to surgery significantly prolonged recurrence-free and distant metastasis…

2025

LITESPARK-011

Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial

2026

Euro-EWING99

A large randomized non-inferiority trial demonstrating that cyclophosphamide is non-inferior to ifosfamide as consolidation therapy for standard-risk localized Ewing sarcoma, offering a more favorabl…

2014

COMMIT

PURPOSE Immunotherapy for frontline mismatch repair–deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC) is effective;

2026

FIND

PURPOSE We hypothesized that a dynamic surveillance strategy guided by circulating tumor DNA (ctDNA) methylation would increase the rate of curative-intent therapy for recurrence in patients with nonm

2026

RADICAL

PURPOSE Bone metastases (BM) occur in approximately 30% of patients with metastatic renal cell carcinoma (mRCC) and are associated with poor survival and symptomatic skeletal events (SSEs).

2026

STELLAR

In patients with locally advanced rectal cancer, short-term radiotherapy followed by neoadjuvant chemotherapy (total neoadjuvant therapy) was non-inferior to standard long-term chemoradiotherapy for…

2022

AAML1831

PURPOSE The Children's Oncology Group phase III clinical trial AAML1831 (ClinicalTrials.gov identifier: NCT04293562 ) evaluated liposomal daunorubicin and cytarabine (CPX-351) versus standard daunorub

2026

BL-B01D1

The first-in-class EGFR-HER3 bispecific antibody-drug conjugate BL-B01D1 demonstrated promising preliminary antitumor activity and a manageable, predominantly hematologic safety profile in heavily pr…

2024

DART

PURPOSE Concurrent platinum-based chemotherapy and radiation therapy (cCRT) followed by consolidative durvalumab is the standard of care (SoC) for fit patients with inoperable, locally advanced non–sm

2026

TRAVERSE

PURPOSE Treatment options for clear cell renal cell carcinoma (ccRCC) refractory to immune checkpoint inhibitors (ICIs) and targeted therapy are needed.

2026

TRIANGLE

In younger patients with mantle cell lymphoma, adding ibrutinib to frontline induction and maintenance significantly improved failure-free survival, and standard ASCT was not superior to an ibrutinib…

2024

ACT-GI

PURPOSE Chemotherapy-induced thrombocytopenia (CIT) is a challenging and common complication of cytotoxic chemotherapy in patients with GI cancers.

2026

FINGER

The FINGER trial demonstrated that a 2-year multidomain lifestyle intervention significantly improves or maintains cognitive functioning in older adults at increased risk for dementia compared to reg…

2015

BRUIN

The phase 1/2 BRUIN trial demonstrated that pirtobrutinib, a highly selective noncovalent BTK inhibitor, is safe and highly active in heavily pretreated B-cell malignancies, overcoming acquired resis…

2021

RATE-AF

In older patients with permanent atrial fibrillation and symptoms of heart failure, low-dose digoxin compared with bisoprolol resulted in no significant difference in quality of life at 6 months, but…

2020

COMPETE

[177Lu]Lu-edotreotide versus everolimus for gastroenteropancreatic neuroendocrine tumours (COMPETE): a phase 3, multicentre, randomised, open-label, superiority trial

2026

eNRGy

In the phase 2 eNRGy trial, zenocutuzumab, a bispecific antibody targeting HER2 and HER3, demonstrated a 30% overall response rate with durable anti-tumor activity and a highly favorable safety profi…

2025

JCOG1008

In patients with postoperative high-risk locally advanced head and neck squamous cell carcinoma, chemoradiotherapy with weekly cisplatin was noninferior to standard 3-weekly cisplatin for overall sur…

2022

RCTS

PURPOSE Clinical data for first-line combination of antibody-drug conjugates (ADC) and immune checkpoint inhibitors in human epidermal growth factor receptor 2 (HER2)–overexpressing advanced gastric o

2026

GOAL-HF1

Safety, pharmacokinetics, and exploratory efficacy of the oral ghrelin receptor agonist AC01 in heart failure with reduced ejection fraction (GOAL-HF1): a randomised, double-blind, placebo-controlled,

2026

ATTRACTION-2

In patients with heavily pretreated advanced gastric or gastroesophageal junction cancer, third-line or later treatment with the PD-1 inhibitor nivolumab significantly improved overall survival compa…

2017

TRACE

In patients with left ventricular systolic dysfunction following an acute myocardial infarction, the ACE inhibitor trandolapril significantly reduces all-cause mortality, cardiovascular death, and pr…

1995

Trastuzumab

The addition of the anti-HER2 monoclonal antibody trastuzumab to standard chemotherapy significantly improved time to progression and overall survival in women with HER2-overexpressing metastatic bre…

2001

NICUSeq

In acutely ill infants with suspected genetic diseases, early whole-genome sequencing doubled the rate of diagnostic yield and significantly increased actionable changes in clinical management compar…

2021

SNAP

In the largest randomized adaptive platform trial for Staphylococcus aureus bacteremia, cefazolin was found to be noninferior to standard antistaphylococcal penicillins for 90-day mortality while sig…

2026

SUCCESSOR-2

Mezigdomide, carfilzomib, and dexamethasone versus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma (SUCCESSOR-2): a phase 3, open-label, randomised controlled tr

2026

REIMAGINE

In a prospective community-based screening study, upfront biparametric MRI detected a substantial number of clinically significant prostate cancers in men with normal PSA levels, demonstrating the fe…

2023

ACHIEVE-2

The ACHIEVE-2 trial demonstrated that 3 months of oxaliplatin-based adjuvant chemotherapy, particularly CAPOX, provided comparable disease-free survival to the standard 6-month regimen for high-risk…

2020

PATHFINDER

A prospective cohort study demonstrating the clinical feasibility of using a blood-based multi-cancer early detection (MCED) test to screen for multiple cancers simultaneously and direct subsequent d…

2023

PRADA

In women receiving adjuvant anthracycline-containing therapy for early breast cancer, concomitant treatment with the angiotensin receptor blocker candesartan protected against early decline in left v…

2016

ABBV-011

In a first-in-human phase 1 trial, the SEZ6-targeting antibody-drug conjugate ABBV-011 demonstrated a manageable safety profile and encouraging preliminary antitumor activity, yielding a 25% objectiv…

2024

Frexalimab

In a phase 2 clinical trial, frexalimab, an Fc-engineered anti-CD40L monoclonal antibody, significantly reduced the number of new gadolinium-enhancing brain lesions in patients with relapsing multipl…

2024

CHOP

The SWOG 8516 trial demonstrated that third-generation intensive chemotherapy regimens were neither more effective nor less toxic than the standard CHOP regimen for advanced non-Hodgkin's lymphoma.

1993

TXI

In an international, multicenter randomized trial, the use of Texture and Color Enhancement Imaging (TXI) during colonoscopy significantly increased the adenoma detection rate compared to standard hi…

2023

NEMIO

PURPOSE To evaluate the efficacy and safety of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) combined with durvalumab ± tremelimumab in patients with muscle-inv

2026

PFA-SHAM

BACKGROUND: Catheter ablation for atrial fibrillation (AF) is one of the most common cardiovascular procedures being performed worldwide.

2026

NOTION-3

In patients with severe aortic stenosis and stable coronary artery disease, performing percutaneous coronary intervention prior to or concurrently with TAVI reduced the composite risk of death, myoca…

2024

TRIBUTE

Single-inhaler triple therapy reduced moderate-severe exacerbations vs LAMA/LABA in symptomatic COPD with prior exacerbations.

2018

BART

PURPOSE To report the primary analysis of a multicenter, phase III randomized trial of adjuvant radiotherapy (RT) after chemotherapy and radical cystectomy (RC) in patients with high-risk muscle-invas

2026

GMMG-HD7

Mass spectrometry (MS) offers a minimally invasive approach for detecting monoclonal proteins in multiple myeloma (MM), but large prospective evaluations remain limited.

2026

GBS3

GBS3 process-outcomes paper: universal late-pregnancy GBS testing was feasible and acceptable in UK maternity units; this paper does not report clinical effectiveness.

2026

SKYLIGHT 1

Fezolinetant NK3 receptor antagonist reduced moderate-severe vasomotor symptoms in menopause vs placebo.

2023

MsFLASH

Escitalopram modestly reduced frequency and severity of menopausal hot flashes vs placebo in non-hormonal trial.

2011

HERS

Estrogen plus progestin did not reduce CHD events in women with established coronary heart disease.

1998

STRIDER

Sildenafil did not improve outcomes in severe early-onset fetal growth restriction and was associated with neonatal harm.

2018

BEAM

Antenatal magnesium sulfate reduced moderate-severe cerebral palsy in surviving infants born very preterm.

2008

MOMS

Prenatal repair of myelomeningocele reduced need for VP shunt and improved motor outcomes vs postnatal repair.

2011

Term Breech

Planned cesarean delivery reduced perinatal mortality/morbidity vs planned vaginal birth for term breech presentation.

2000

PRISM

Vaginal progesterone did not improve overall live birth rate but benefitted women with prior miscarriages.

2019

Meis 17P

17-OHPC weekly reduced recurrent preterm birth vs placebo in women with prior spontaneous preterm delivery.

2003

PATENT-1

Riociguat soluble guanylate cyclase stimulator improved exercise capacity and clinical outcomes in PAH.

2013

STELLAR

Sotatercept added to background therapy improved 6-minute walk distance in pulmonary arterial hypertension.

2023

BOREAS

Dupilumab reduced exacerbations and improved lung function in COPD with type 2 inflammation (elevated eosinophils).

2023

INBUILD

Nintedanib slowed FVC decline in progressive fibrosing non-IPF interstitial lung diseases.

2019

INPULSIS-2

Nintedanib slowed annual FVC decline in idiopathic pulmonary fibrosis with manageable side effects.

2014

PEPTIC

Pantoprazole did not significantly reduce 90-day mortality vs histamine-2 blocker in ICU patients receiving mechanical ventilation.

2020

VITAL-DEP

Vitamin D3 2000 IU daily did not reduce incident depression in older adults without baseline depression.

2020

SURMOUNT-2

Tirzepatide produced significant weight loss in adults with obesity and type 2 diabetes vs placebo.

2023

Cerclage (Owen 2009)

Ultrasound-indicated cerclage for cervix <25 mm after prior preterm birth — no significant drop in birth <35 weeks overall; fewer previable births and perinatal deaths.

2009

HAPO

HAPO: maternal glucose levels below diabetes thresholds were associated with adverse pregnancy outcomes.

2008

WOMAN

Tranexamic acid reduced death due to bleeding in women with postpartum hemorrhage when given early.

2017

ASPRE

Low-dose aspirin in high-risk women reduced preterm preeclampsia vs placebo in first-trimester screening cohort.

2017

CHAP

Treating mild chronic hypertension to BP <140/90 reduced adverse pregnancy outcomes without harming fetal growth.

2022

CHIPS

Tight blood pressure control in non-severe pregnancy hypertension did not improve perinatal outcomes vs less tight.

2015

MAGPIE

Magnesium sulfate halved the risk of eclampsia in women with preeclampsia compared with placebo.

2002

ALPS

Antenatal betamethasone in late preterm pregnancy reduced respiratory morbidity in newborns vs placebo.

2016

CHEST-1

Riociguat improved exercise capacity and hemodynamics in inoperable CTEPH or persistent PH after PEA.

2013

AMBITION

Initial combination ambrisentan plus tadalafil reduced clinical failure vs monotherapy in treatment-naive PAH.

2015

GRIPHON

Selexipag oral prostacyclin receptor agonist reduced morbidity/mortality events in pulmonary arterial hypertension.

2015

SERAPHIN

Macitentan reduced morbidity/mortality composite vs placebo in pulmonary arterial hypertension.

2013

NOTUS

NOTUS confirmed dupilumab reduced exacerbations in COPD with type 2 inflammation, supporting FDA approval.

2024

TRAVERSE

Long-term dupilumab maintained efficacy and safety in patients with moderate-severe asthma over 96 weeks.

2022

QUEST

Dupilumab reduced exacerbations and improved FEV1 in moderate-severe uncontrolled asthma, especially eosinophilic.

2018

NAVIGATOR

Tezepelumab anti-TSLP reduced annualized asthma exacerbations vs placebo in severe uncontrolled asthma regardless of phenotype.

2021

SIRIUS

Mepolizumab reduced oral corticosteroid dose while maintaining asthma control in severe eosinophilic asthma.

2014

MENSA

Mepolizumab reduced clinically significant asthma exacerbations in patients with severe eosinophilic asthma.

2014

DREAM

Mepolizumab anti-IL-5 reduced eosinophilic asthma exacerbations vs placebo in severe disease.

2012

SENSCIS

Nintedanib slowed FVC decline in systemic sclerosis-associated interstitial lung disease over 52 weeks.

2019

POET-COPD

Tiotropium reduced time to first moderate-severe COPD exacerbation vs salmeterol over 1 year.

2011

WISDOM

Stepwise withdrawal of ICS in severe COPD did not increase exacerbations but slightly worsened lung function.

2014

FLAME

LABA/LAMA reduced COPD exacerbations vs ICS/LABA in patients with history of exacerbations.

2016

ETHOS

Budesonide/glycopyrrolate/formoterol triple therapy reduced exacerbations and all-cause mortality vs dual LAMA/LABA in COPD.

2020

IMPACT

Fluticasone/umeclidinium/vilanterol triple therapy reduced exacerbations vs dual therapy in symptomatic COPD.

2018

UPLIFT

Tiotropium did not slow FEV1 decline but improved lung function and quality of life over 4 years in COPD.

2008

TORCH

Salmeterol/fluticasone combination did not significantly reduce all-cause mortality vs placebo in moderate-severe COPD.

2007

CRASH-3

Tranexamic acid reduced head-injury-related death in patients with mild/moderate TBI treated early.

2019

CRASH-2

Early IV tranexamic acid reduced all-cause and bleeding-related mortality in adult trauma patients with hemorrhage.

2010

65 trial

Permissive hypotension (MAP 60-65) did not significantly reduce 90-day mortality vs usual care in older sepsis patients.

2020

EPaNIC

Late initiation of parenteral nutrition was superior to early in adult ICU patients; less infection and faster recovery.

2011

TARGET

Energy-dense (1.5 kcal/mL) enteral nutrition did not improve 90-day mortality vs routine in mechanically ventilated adults.

2018

SUP-ICU

Pantoprazole did not significantly reduce 90-day mortality vs placebo in adult ICU patients at risk for GI bleeding.

2018

NICE-SUGAR

Intensive glucose control (81-108 mg/dL) increased mortality vs conventional (<180 mg/dL) in adult ICU patients.

2009

PLUS

Balanced multielectrolyte solution did not significantly reduce 90-day mortality vs saline in critically ill adults.

2022

BaSICS

Balanced solution did not significantly reduce 90-day mortality vs saline in heterogeneous Brazilian ICU patients.

2021

SALT-ED

Balanced crystalloids reduced major adverse kidney events vs saline in non-critically ill ED patients.

2018

CHEST

Hydroxyethyl starch 130/0.4 increased renal replacement therapy vs saline in critically ill adults.

2012

6S

Hydroxyethyl starch 130/0.42 increased death and renal replacement therapy vs Ringer's acetate in severe sepsis.

2012

SAFE

4% albumin and 0.9% saline produced similar 28-day mortality in heterogeneous ICU population.

2004

EOLIA

Early VV-ECMO did not significantly reduce 60-day mortality vs conventional care in very severe ARDS.

2018

ROSE

Routine early cisatracurium did not reduce 90-day mortality vs usual care with lighter sedation in moderate-severe ARDS.

2019

ART

Lung recruitment maneuver and titrated PEEP increased mortality vs low-PEEP strategy in moderate-severe ARDS.

2017

PROSEVA

Early prolonged prone positioning reduced 28-day mortality in severe ARDS (PaO2/FiO2 <150).

2013

ProMISe

EGDT did not reduce 90-day mortality vs usual resuscitation in early septic shock in UK NHS hospitals.

2015

ARISE

Early goal-directed therapy did not reduce 90-day mortality vs usual care in septic shock.

2014

SOAP-II

Norepinephrine reduced arrhythmias vs dopamine in shock; mortality similar overall but dopamine worse in cardiogenic shock.

2010

VASST

Adding vasopressin to norepinephrine did not reduce mortality vs norepinephrine alone in septic shock.

2008

CORTICUS

Hydrocortisone did not improve survival vs placebo in septic shock regardless of corticotropin test response.

2008

APROCCHSS

Hydrocortisone plus fludrocortisone reduced 90-day mortality in septic shock with high severity scores.

2018

TRISS

Restrictive transfusion threshold (Hgb 7) similar mortality to liberal (Hgb 9) in septic shock patients.

2014

TRICC

Restrictive RBC transfusion (Hgb 7) was non-inferior or superior to liberal (Hgb 10) in critically ill adults.

1999

NORDICC

Invitation to colonoscopy reduced colorectal cancer risk modestly; effect attenuated by limited uptake.

2022

NELSON

Volume CT lung cancer screening reduced lung cancer mortality in male former and current smokers in Europe.

2020

WHISH

WHISH design and baseline paper: a pragmatic physical-activity trial in 49,331 older women; this paper reports no outcomes.

2021

PREDIMED

Mediterranean diet with olive oil or nuts reduced major CV events vs low-fat diet in high-risk adults.

2013

INTERACT2

Intensive systolic BP lowering (target <140 mmHg) in acute ICH trended toward better functional outcomes.

2013

FIELD

Fenofibrate did not significantly reduce coronary events in T2D, with possible benefit in dyslipidemic patients.

2005

PARAMEDIC2

In adults with out-of-hospital cardiac arrest, the use of epinephrine resulted in a significantly higher rate of 30-day survival and Return of Spontaneous Circulation (ROSC) than placebo, but did not…

2018

WSG TP-II

The WSG-TP-II trial found that neoadjuvant de-escalated chemotherapy (paclitaxel) combined with dual HER2 blockade achieved a significantly higher pathological complete response rate than endocrine t…

2023

MINT

In patients with acute myocardial infarction and anemia, a liberal blood transfusion strategy did not significantly reduce the 30-day risk of recurrent myocardial infarction or death compared to a re…

2023

PURE

PURE study: high carbohydrate intake associated with higher mortality; total fat with lower mortality globally.

2017

SSaSS

SSaSS: salt substitute with reduced sodium and added potassium reduced stroke and CV events in rural China.

2021

TONE

Weight loss and sodium reduction reduced need for antihypertensive medication in older adults with HTN.

1998

DASH-Sodium

Reducing sodium intake plus DASH diet lowered blood pressure more than either intervention alone.

2001

DASH

DASH dietary pattern lowered systolic and diastolic blood pressure substantially in adults with high-normal/Stage 1 HTN.

1997

ALLHAT-LLT

Pravastatin did not significantly reduce all-cause mortality vs usual care in hypertensive adults aged 55+.

2002

PolyIran

Polypill containing aspirin, statin, and antihypertensives reduced major CV events in Iranian rural cohort.

2019

TIPS-3

TIPS-3: polypill plus aspirin reduced CV events vs placebo in intermediate-risk adults without CVD.

2021

VITAL-Bone

Vitamin D3 2000 IU daily did not reduce fractures in generally healthy older adults without low BMD or vitamin D deficiency.

2022

D2d

Vitamin D3 4000 IU daily did not significantly reduce progression to T2D in adults with prediabetes.

2019

WHI Diet

Low-fat dietary pattern did not reduce breast cancer, colorectal cancer, or CHD over 8 years in postmenopausal women.

2006

PROVE-HF

PROVE-HF (single-arm): after starting sacubitril-valsartan in HFrEF, NT-proBNP fell and the fall tracked reverse remodeling — higher LVEF, smaller LV volumes at 12 months.

2019

COMPASS

Low-dose rivaroxaban plus aspirin reduced major CV events vs aspirin alone in stable atherosclerotic disease.

2017

MEGA

Pravastatin reduced coronary events in Japanese adults with hypercholesterolemia without prior CVD.

2006

PROSPER

Pravastatin reduced coronary events in older adults at risk for CVD with mixed effects in primary prevention.

2002

SPRINT-MIND

Intensive BP control (target <120 mmHg) reduced MCI and combined MCI/dementia but not probable dementia alone.

2019

EAGLES

Varenicline and bupropion did not increase neuropsychiatric adverse events vs NRT/placebo in smokers.

2016

SHEP

Antihypertensive drug treatment of isolated systolic hypertension in elderly reduced stroke and CV events.

1991

PREDIMED-Plus

PREDIMED-Plus interim analysis: an intensive energy-reduced Mediterranean diet program improved diet adherence at 12 months vs usual advice; this paper reports no cardiovascular outcomes.

2019

VITAL-Rhythm

Vitamin D and omega-3 did not reduce incidence of atrial fibrillation in primary prevention population.

2020

VITAL

Vitamin D3 2000 IU and omega-3 1g daily did not reduce major CV events or cancer vs placebo over 5 years.

2019

SANAD I

SANAD I: lamotrigine had better outcomes than carbamazepine for partial-onset seizures; valproate best for generalized.

2007

PROMISE-2

IV eptinezumab reduced monthly migraine days vs placebo in chronic migraine prevention.

2020

EVOLVE-1

Galcanezumab (anti-CGRP antibody) reduced monthly migraine headache days vs placebo in episodic migraine prevention.

2018

STRIVE

Erenumab CGRP receptor antagonist reduced monthly migraine days vs placebo in episodic migraine prevention.

2017

MCI-186 Study 19

MCI-186-19: IV edaravone slowed functional decline in early-stage ALS with preserved respiratory function.

2017

CENTAUR

AMX0035 slowed functional decline modestly vs placebo in ALS; later withdrawn after PHOENIX failed.

2020

VALOR

Tofersen did not significantly improve ALSFRS-R in SOD1 ALS but lowered neurofilament; conditional FDA approval.

2022

SUNBEAM

Ozanimod (S1P modulator) reduced relapse rate vs interferon beta-1a in relapsing-remitting MS.

2019

FREEDOMS

Oral fingolimod reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.

2010

CLARITY

Oral cladribine reduced annualized relapse rate vs placebo in relapsing-remitting multiple sclerosis.

2010

ORATORIO

Ocrelizumab slowed disability progression vs placebo in primary progressive multiple sclerosis.

2017

OPERA I/II

Ocrelizumab reduced annualized relapse rate vs interferon beta-1a in relapsing-remitting multiple sclerosis.

2017

EMERGE/ENGAGE

EMERGE/ENGAGE Phase 3 trials of aducanumab in early Alzheimer's gave mixed results; FDA approved controversially.

2022

TRAILBLAZER-ALZ 2

Donanemab slowed cognitive and functional decline in early symptomatic Alzheimer's with amyloid pathology.

2023

CLARITY-AD

Lecanemab anti-amyloid antibody slowed clinical decline in early Alzheimer's disease over 18 months.

2022

ANNEXA-4

Andexanet alfa effectively reversed anti-factor Xa activity in patients with major bleeding on apixaban/rivaroxaban.

2019

DEFUSE-2

Perfusion-DWI mismatch identified stroke patients more likely to benefit from endovascular reperfusion.

2012

CRYSTAL-AF

Insertable cardiac monitor detected AF in cryptogenic stroke patients more often than conventional monitoring.

2014

SPS3

Dual antiplatelet therapy after lacunar stroke increased bleeding without reducing recurrent stroke.

2012

ENCHANTED

Low-dose alteplase did not show non-inferiority but reduced symptomatic hemorrhage vs standard dose.

2016

ATACH-II

Intensive systolic BP lowering (110-139 mmHg) did not improve outcomes vs standard in acute ICH.

2016

SOCRATES

Ticagrelor was not superior to aspirin for prevention of recurrent vascular events after acute ischemic stroke.

2016

THALES

Ticagrelor plus aspirin reduced stroke/death vs aspirin alone after minor stroke or high-risk TIA.

2020

CHANCE

Clopidogrel plus aspirin for 21 days reduced 90-day stroke vs aspirin alone in minor stroke/TIA in China.

2013

POINT

Clopidogrel plus aspirin reduced ischemic events vs aspirin alone after minor stroke or high-risk TIA.

2018

RESILIENT

Mechanical thrombectomy improved functional outcomes vs medical therapy alone in middle-income country setting.

2020

TIMELESS

Tenecteplase in 4.5-24h window with perfusion mismatch did not improve functional outcomes vs placebo.

2024

AcT

Tenecteplase non-inferior to alteplase for functional outcomes in acute ischemic stroke within 4.5 hours.

2022

THRACE

Mechanical thrombectomy after IV tPA improved 3-month functional outcomes in large vessel occlusion stroke.

2016

SWIFT-PRIME

Stent retriever thrombectomy with IV tPA improved functional outcomes vs tPA alone in proximal anterior stroke.

2015

REVASCAT

Mechanical thrombectomy up to 8 hours improved functional outcomes in proximal anterior circulation occlusion.

2015

EXTEND-IA

Thrombectomy after IV tPA in patients with perfusion mismatch improved reperfusion and functional outcomes.

2015

ESCAPE

Rapid endovascular thrombectomy with collaterals selection reduced disability in proximal anterior stroke.

2015

MR CLEAN

Endovascular thrombectomy within 6 hours improved functional outcomes in proximal anterior circulation stroke.

2015

IST-3

IV alteplase up to 6 hours did not significantly improve primary outcome but suggested benefit in selected patients.

2012

ECASS-3

IV alteplase between 3 and 4.5 hours improved functional outcomes in acute ischemic stroke vs placebo.

2008

BEACON

BEACON: bardoxolone methyl in stage 4 CKD with T2D was halted for increased HF and CV events.

2013

ACCORD-Lipid

Adding fenofibrate to simvastatin did not reduce CV events in T2D, except in dyslipidemic subgroup.

2010

VERIFY

Early combination metformin/vildagliptin delayed treatment failure vs sequential therapy in newly diagnosed T2D.

2019

High-Dose Flu Vaccine (FIM12)

High-dose inactivated influenza vaccine more efficacious than standard dose in adults aged 65 and older.

2014

FLAURA2

Osimertinib plus chemo improved PFS vs osimertinib alone in untreated EGFR-mutated advanced NSCLC.

2023

RELATIVITY-047

Relatlimab plus nivolumab (LAG-3 + PD-1) improved PFS vs nivolumab alone in untreated advanced melanoma.

2022

CANTATA-SU

Canagliflozin non-inferior to glimepiride for HbA1c reduction with weight loss in T2D on metformin.

2013

EMPULSE

Empagliflozin initiated during hospitalization for acute HF improved clinical benefit composite at 90 days.

2022

SELECT (kidney)

Semaglutide reduced kidney composite events in overweight/obese adults with established CVD without diabetes.

2024

STEP-HFpEF DM

Semaglutide improved symptoms and weight in obese HFpEF patients with type 2 diabetes.

2024

SCALE

Liraglutide 3.0 mg produced clinically meaningful weight loss vs placebo in adults with obesity over 56 weeks.

2015

ACCORD-MIND

Intensive glucose control did not improve cognitive outcomes vs standard therapy in T2D over 40 months.

2011

Look AHEAD (remission)

Look AHEAD lifestyle intervention produced T2D remission in a small but meaningful proportion of participants.

2012

ACHIEVE-1

Oral non-peptide GLP-1 receptor agonist orforglipron lowered HbA1c and weight in T2D.

2025

OASIS-1

Oral semaglutide 50 mg produced 15% weight loss in adults with obesity over 68 weeks.

2023

STEP 5

Weekly semaglutide 2.4 mg produced sustained ~15% weight loss over 2 years in adults with obesity.

2022

DPP

Lifestyle intervention and metformin reduced incidence of T2D in adults with impaired glucose tolerance.

2002

LookAHEAD

Intensive lifestyle intervention produced weight loss but did not reduce CV events in overweight/obese T2D.

2013

GRADE

Liraglutide and insulin glargine best maintained glycemic targets compared with glimepiride or sitagliptin in T2D.

2022

SURPASS-4

Tirzepatide produced greater HbA1c/weight reductions vs glargine in T2D with high CV risk; CV outcomes neutral.

2021

SURPASS-3

Tirzepatide produced greater HbA1c and weight reductions vs insulin degludec in T2D inadequately controlled.

2021

SURPASS-2

Tirzepatide showed greater HbA1c and weight reduction than semaglutide in T2D on metformin.

2021

SURMOUNT-1

Tirzepatide produced 15-22% weight loss in adults with obesity without diabetes over 72 weeks.

2022

DEVOTE

Insulin degludec was non-inferior to glargine for MACE and reduced severe hypoglycemia in T2D.

2017

ORIGIN

Insulin glargine targeting normal fasting glucose did not change CV outcomes in early dysglycemia/T2D.

2012

CARMELINA

Linagliptin was non-inferior to placebo for CV and kidney outcomes in T2D at high vascular risk.

2019

CAROLINA

Linagliptin was non-inferior to glimepiride for major adverse cardiovascular events in T2D.

2019

ELIXA

Lixisenatide was non-inferior to placebo for cardiovascular events in T2D after recent ACS.

2015

Harmony Outcomes

Albiglutide reduced major adverse CV events in T2D patients with established cardiovascular disease.

2018

AMPLITUDE-O

Efpeglenatide reduced MACE and renal events in T2D with prior CVD or kidney disease.

2021

PIONEER-6

Oral semaglutide was non-inferior to placebo for MACE in T2D at high cardiovascular risk.

2019

REWIND

Dulaglutide reduced major adverse cardiovascular events in T2D with established CVD or risk factors.

2019

EXAMINE

Alogliptin was non-inferior to placebo for major cardiovascular events in T2D after recent ACS.

2013

SAVOR-TIMI 53

Saxagliptin was non-inferior to placebo for ischemic events but increased heart failure hospitalization in T2D.

2013

TECOS

Sitagliptin was non-inferior to placebo for major cardiovascular events in T2D with established CVD.

2015

ACCORD (glycemia)

Intensive glucose control to HbA1c <6% increased mortality vs standard in T2D with CVD risk.

2008

VADT

Intensive vs standard glucose control in long-standing T2D did not reduce major CV events.

2009

ADVANCE

Intensive glucose control (HbA1c 6.5%) reduced nephropathy but not major macrovascular events in T2D.

2008

PARTNER2

PARTNER2: zero linked HIV transmissions among gay serodifferent couples with a virally suppressed partner across 76,088 condomless sex acts (U=U).

2019

CAPiTA

PCV13 prevented vaccine-type community-acquired pneumococcal pneumonia in adults aged 65+.

2015

PNEUMOSIL

PNEUMOSIL 10-valent pneumococcal conjugate vaccine was non-inferior to Synflorix (PHiD-CV) for IgG responses in Gambian infants.

2020

ACTT-2

Baricitinib plus remdesivir shortened recovery time and improved outcomes vs remdesivir in hospitalized COVID-19.

2021

COMET-ICE

COMET-ICE: sotrovimab reduced progression to hospitalization or death in high-risk non-hospitalized COVID-19.

2021

PREVENT TB

TBTC Study 26 / PREVENT TB: 12-dose weekly rifapentine-isoniazid (3HP) non-inferior to 9-month isoniazid.

2011

FLU-IVIG

Anti-influenza hyperimmune IV immunoglobulin did not improve outcomes in hospitalized influenza patients.

2019

OFLOTUB

Gatifloxacin-containing 4-month regimen for drug-susceptible TB was inferior to standard 6-month therapy.

2014

STREAM

9-month MDR-TB regimen non-inferior to longer WHO regimen with similar safety, more affordable.

2019

Nix-TB

BPaL regimen (bedaquiline, pretomanid, linezolid) showed high cure rates in XDR and pretreated MDR-TB.

2020

Study 31/A5349

Study 31/A5349: 4-month rifapentine/moxifloxacin regimen non-inferior to standard 6-month therapy for drug-susceptible TB.

2021

REMoxTB

4-month moxifloxacin-containing regimens failed noninferiority to standard 6-month therapy for drug-sensitive TB — more relapses despite faster culture conversion.

2014

C-EDGE

Elbasvir-grazoprevir achieved high SVR12 rates in chronic HCV genotype 1, 4, 6 treatment-naive patients.

2015

ION-1

Ledipasvir-sofosbuvir achieved >95% SVR12 in treatment-naive genotype 1 HCV without ribavirin.

2014

ASTRAL-1

Sofosbuvir-velpatasvir for 12 weeks achieved 99% SVR12 in HCV genotypes 1, 2, 4, 5 and 6 (genotype 3 was ASTRAL-3).

2015

MERINO

Piperacillin-tazobactam inferior to meropenem for ceftriaxone-resistant E. coli/Klebsiella bacteremia mortality.

2018

MATISSE

Maternal RSVpreF vaccination prevented medically attended severe RSV in infants up to 6 months.

2023

MELODY

Single-dose nirsevimab reduced medically attended RSV lower respiratory illness in healthy infants.

2022

RENOIR

Bivalent RSVpreF vaccine prevented RSV-associated lower respiratory illness in adults aged 60+.

2023

ZOE-50/70

Recombinant adjuvanted zoster vaccine (Shingrix) reduced herpes zoster incidence by ~90% in older adults.

2016

R21

R21/Matrix-M malaria vaccine showed high efficacy against clinical malaria in African children Phase 3.

2023

RTS,S

RTS,S/AS01 malaria vaccine provided partial protection against clinical and severe malaria in African children.

2015

MOVe-OUT

Molnupiravir reduced hospitalization/death in non-hospitalized adults with mild-moderate COVID-19 at risk.

2022

iPrEx

Oral TDF/FTC pre-exposure prophylaxis reduced HIV acquisition in men who have sex with men.

2010

MajesTEC-1

Teclistamab BCMA-CD3 bispecific produced durable responses in heavily pretreated relapsed/refractory myeloma.

2022

NOAH

Neoadjuvant trastuzumab plus chemo improved event-free survival in HER2+ locally advanced breast cancer.

2010

PAOLA-1

Olaparib plus bevacizumab maintenance improved PFS in advanced ovarian cancer, especially HRD-positive.

2019

CLEAR

Lenvatinib plus pembrolizumab improved PFS and OS vs sunitinib in advanced renal cell carcinoma.

2021

WOEST

Warfarin + clopidogrel vs triple therapy after PCI in patients on OAC — reduced bleeding without ischemic penalty.

2013

ENSEMBLE

Single-dose Ad26.COV2.S vaccine was efficacious against moderate-severe COVID-19 across multiple regions.

2021

ChAdOx1

ChAdOx1 nCoV-19 adenoviral COVID-19 vaccine showed efficacy against symptomatic disease in pooled Phase 3.

2021

NVX-CoV2373

Novavax NVX-CoV2373 protein-subunit vaccine showed ~90% efficacy against symptomatic COVID-19 in Phase 3.

2021

ACTIV-3

Bamlanivimab did not improve outcomes in hospitalized adults with COVID-19 and was discontinued for futility.

2021

PANORAMIC

Molnupiravir did not reduce hospitalization/death in vaccinated high-risk outpatients with COVID-19.

2022

EPIC-HR

Nirmatrelvir-ritonavir reduced COVID-19 hospitalization or death by ~89% in high-risk unvaccinated outpatients.

2022

COV-BARRIER

Baricitinib reduced 28-day mortality in hospitalized adults with COVID-19 requiring oxygen.

2021

EMPACTA

Tocilizumab reduced progression to mechanical ventilation or death in hospitalized COVID-19 pneumonia.

2021

COVACTA

Tocilizumab in hospitalized severe COVID-19 pneumonia did not improve clinical status at day 28.

2021

REMAP-CAP

Tocilizumab and sarilumab improved organ-support-free days in critically ill COVID-19 patients.

2021

PURPOSE-2

Twice-yearly lenacapavir reduced HIV incidence vs daily oral TDF/FTC in MSM and gender-diverse populations.

2024

PURPOSE-1

Twice-yearly injectable lenacapavir prevented all HIV infections in cisgender women in sub-Saharan Africa.

2024

HPTN-083

Injectable cabotegravir every 8 weeks more effective than oral TDF/FTC for HIV PrEP in MSM/TGW.

2021

DISCOVER

F/TAF non-inferior to F/TDF for HIV PrEP in men and transgender women, with better renal/bone safety.

2020

SMART

Continuous ART was superior to CD4-guided treatment interruption for opportunistic disease and death.

2006

TEMPRANO

Early ART and isoniazid prophylaxis reduced severe illness/death in HIV-positive adults in West Africa.

2015

START

Immediate ART initiation reduced serious AIDS/non-AIDS events in HIV-positive adults with CD4 above 500.

2015

HPTN-052

Early ART in HIV-positive partner cut HIV transmission to serodiscordant partners by ~96%.

2011

MAGIC

Perioperative ECF chemotherapy improved OS vs surgery alone in resectable gastric/lower esophageal cancer.

2006

CROSS

Neoadjuvant chemoradiation improved OS vs surgery alone in resectable esophageal cancer.

2012

EPCORE NHL-1

Epcoritamab CD20-CD3 bispecific induced durable responses in relapsed/refractory large B-cell lymphoma.

2023

TOURMALINE-MM1

Ixazomib added to Rd improved PFS in relapsed/refractory multiple myeloma.

2016

EMILIA

T-DM1 improved PFS and OS vs lapatinib/capecitabine in HER2+ advanced breast cancer pretreated.

2012

AURA3

Osimertinib improved PFS vs chemo in T790M-positive EGFR NSCLC after first-line TKI failure.

2017

IDEA

IDEA pooled analysis suggested 3 months of adjuvant CAPOX non-inferior to 6 months in low-risk stage III colon cancer.

2018

X-ACT

Adjuvant capecitabine non-inferior to 5-FU/LV in stage III colon cancer with better tolerability.

2005

MOSAIC

Adjuvant FOLFOX improved DFS over 5-FU/LV in resected stage II/III colon cancer; established standard.

2004

CheckMate-577

Adjuvant nivolumab doubled disease-free survival in resected esophageal/GEJ cancer with residual disease.

2021

KEYNOTE-590

Pembrolizumab plus chemo improved OS in advanced esophageal and esophagogastric junction cancer.

2021

PALOMA-3

Palbociclib plus fulvestrant improved PFS in pretreated HR+/HER2- advanced breast cancer.

2015

MONALEESA-2

Ribociclib plus letrozole prolonged PFS in postmenopausal HR+/HER2- advanced breast cancer; OS benefit was reported in 2022.

2016

PALOMA-2

Palbociclib plus letrozole improved PFS in postmenopausal HR+/HER2- metastatic breast cancer first-line.

2016

OlympiA

One year of adjuvant olaparib improved invasive DFS in BRCA-mutated high-risk early breast cancer.

2021

RAPIDO

Short-course RT followed by chemo before surgery reduced disease-related treatment failure in rectal cancer.

2020

PRODIGE 23

Neoadjuvant FOLFIRINOX before chemoradiation improved DFS in locally advanced rectal cancer.

2021

NAPOLI-3

NALIRIFOX improved OS vs gem/nab-paclitaxel in untreated metastatic pancreatic adenocarcinoma.

2023

TOPAZ-1

Durvalumab plus chemo improved OS vs chemo alone in advanced biliary tract cancer first-line.

2022

POSEIDON

Tremelimumab plus durvalumab plus chemo improved OS vs chemo alone in untreated metastatic NSCLC.

2022

ALEX

Alectinib improved PFS vs crizotinib as first-line therapy in advanced ALK-positive NSCLC.

2017

CROWN

Lorlatinib improved PFS vs crizotinib in previously untreated advanced ALK-positive NSCLC.

2020

TROPION-Lung01

Dato-DXd improved PFS modestly vs docetaxel in previously treated advanced NSCLC, especially nonsquamous.

2023

PACIFIC-2

Concurrent durvalumab with chemoradiation in unresectable stage III NSCLC did not improve PFS vs sequential.

2024

KRYSTAL-1

Adagrasib produced a 42.9% response rate in previously treated KRAS G12C-mutated NSCLC, with intracranial activity.

2022

CodeBreaK 100

Sotorasib showed clinical activity in KRAS G12C-mutated advanced NSCLC, first KRAS-targeted approval.

2021

MARIPOSA

Amivantamab plus lazertinib improved PFS vs osimertinib in first-line EGFR-mutated advanced NSCLC.

2023

MAGNITUDE

Niraparib plus abiraterone improved PFS in HRR-positive metastatic castration-resistant prostate cancer.

2022

PROfound

Olaparib improved PFS and OS vs enzalutamide/abi in HRR-mutated metastatic castration-resistant prostate cancer.

2020

NOVA

Niraparib maintenance improved PFS in platinum-sensitive recurrent ovarian cancer, regardless of BRCA status.

2016

PRIMA

Niraparib maintenance improved PFS in newly diagnosed advanced ovarian cancer regardless of BRCA status.

2019

SOLO-1

Olaparib maintenance dramatically improved PFS in newly diagnosed BRCA-mutated advanced ovarian cancer.

2018

EV-302

Enfortumab vedotin plus pembrolizumab improved OS and PFS vs chemo in untreated advanced urothelial carcinoma.

2023

CheckMate-214

Nivolumab plus ipilimumab improved OS vs sunitinib in intermediate/poor-risk advanced renal cell carcinoma.

2018

KEYNOTE-426

Pembrolizumab plus axitinib improved OS and PFS vs sunitinib in advanced renal cell carcinoma.

2019

KEYNOTE-054

Adjuvant pembrolizumab improved recurrence-free survival in resected high-risk stage III melanoma.

2018

COMBI-AD

Adjuvant dabrafenib plus trametinib improved relapse-free survival in BRAF-mutant resected stage III melanoma.

2017

MAIA

Daratumumab plus Rd improved PFS and depth of response in transplant-ineligible newly diagnosed myeloma; OS immature at this report.

2019

ADAURA

Adjuvant osimertinib in resected EGFR-mutant NSCLC showed major DFS benefit; established adjuvant TKI standard.

2020

TRILUMINATE

Tricuspid TEER vs medical therapy in severe symptomatic TR — improved quality of life, neutral hard endpoints.

2023

COLCOT

Low-dose colchicine vs placebo within 30 days of MI — reduced ischemic CV events.

2019

ECHELON-1

Brentuximab vedotin plus AVD improved PFS over ABVD in previously untreated stage III/IV Hodgkin lymphoma.

2018

POLARIX

Pola-R-CHP improved PFS vs R-CHOP in previously untreated intermediate/high-risk DLBCL.

2022

CASTOR

Daratumumab added to bortezomib/dex improved PFS in relapsed or refractory multiple myeloma.

2016

ALCYONE

Daratumumab plus VMP improved PFS in transplant-ineligible newly diagnosed multiple myeloma.

2018

CARTITUDE-4

Cilta-cel improved PFS vs standard care in lenalidomide-refractory multiple myeloma after 1-3 lines.

2023

CARTITUDE-1

Cilta-cel BCMA CAR-T produced high response rates and durable remissions in heavily pretreated myeloma.

2021

KarMMa

Ide-cel BCMA CAR-T showed deep responses in heavily pretreated relapsed/refractory multiple myeloma.

2021

ZUMA-7

Axi-cel improved event-free survival vs standard care as second-line therapy in relapsed/refractory LBCL.

2022

ZUMA-1

Axi-cel CAR-T showed durable responses in refractory large B-cell lymphoma, leading to FDA approval.

2017

RUBY

Dostarlimab plus chemo improved PFS in advanced endometrial cancer, especially dMMR/MSI-H tumors.

2023

KEYNOTE-826

Pembrolizumab plus chemo improved OS in persistent, recurrent, or metastatic cervical cancer.

2021

ARASENS

Darolutamide added to ADT plus docetaxel improved OS in metastatic hormone-sensitive prostate cancer.

2022

TITAN

Apalutamide added to ADT improved OS and radiographic PFS in metastatic castration-sensitive prostate cancer.

2019

LATITUDE

Abiraterone plus prednisone added to ADT improved OS in newly diagnosed high-risk metastatic hormone-sensitive prostate cancer.

2017

STAMPEDE (docetaxel)

STAMPEDE: adding docetaxel to first-line hormone therapy improved survival in advanced prostate cancer; zoledronic acid did not.

2016

CheckMate-649

Nivolumab plus chemo improved OS vs chemo alone in advanced HER2-negative gastric/GEJ adenocarcinoma.

2021

CALGB 80405

Cetuximab and bevacizumab plus chemo showed similar OS in first-line KRAS wild-type metastatic colorectal cancer.

2017

MINDACT

MammaPrint genomic test identified breast cancer patients who could safely skip adjuvant chemotherapy.

2016

TAILORx

Endocrine therapy alone non-inferior to chemo-endocrine in HR+/HER2- node-negative breast cancer with mid-range RS.

2018

HER2CLIMB

Tucatinib added to trastuzumab/capecitabine in HER2+ metastatic breast cancer improved OS, including brain metastases.

2020

ASCENT

Sacituzumab govitecan improved OS vs chemo in pretreated metastatic triple-negative breast cancer.

2021

TROPiCS-02

Sacituzumab govitecan improved PFS vs chemotherapy in pretreated HR+/HER2- metastatic breast cancer; OS not yet mature in this report.

2022

DESTINY-Breast04

T-DXd improved OS in HER2-low metastatic breast cancer, establishing HER2-low as a treatable category.

2022

DESTINY-Breast03

Trastuzumab deruxtecan vs T-DM1 in HER2+ metastatic breast cancer showed dramatic PFS and OS benefit.

2022

monarchE

Adjuvant abemaciclib plus endocrine therapy in high-risk HR+/HER2- early breast cancer improved invasive DFS.

2020

KEYNOTE-522

Neoadjuvant pembrolizumab plus chemo in early triple-negative breast cancer improved pCR and event-free survival.

2020

CheckMate-816

Neoadjuvant nivolumab plus chemo before resection in NSCLC improved pCR and event-free survival.

2022

IMpower010

Adjuvant atezolizumab after resection in stage II-IIIA NSCLC improved DFS in PD-L1 positive disease.

2021

OPTIC

Amiodarone + beta-blocker vs sotalol vs beta-blocker alone for ICD shock prevention — amiodarone combo most effective.

2006

PARTITA

VT ablation after first appropriate ICD shock vs continued medical therapy — reduced death/VT storm.

2022

VANISH

Catheter ablation vs escalated antiarrhythmic therapy in recurrent VT — reduced composite of death/VT storm/ICD shocks.

2016

MADIT-RIT

High-rate or delayed ICD therapy vs conventional programming — reduced inappropriate shocks and mortality.

2012

PERIOP-2

LMWH bridging vs placebo during warfarin interruption in high-risk AF/mechanical valves — no benefit, more bleeding.

2021

PAUSE

Standardized DOAC interruption strategy in AF undergoing surgery — low rates of bleeding and thromboembolism.

2019

BRIDGE

Bridging anticoagulation vs no bridging during warfarin interruption in AF — no thromboembolism reduction, more bleeding.

2015

ENTRUST-AF-PCI

Edoxaban-based dual therapy vs warfarin triple therapy after PCI in AF — non-inferior bleeding endpoint.

2019

PIONEER-AF-PCI

Rivaroxaban-based vs warfarin triple therapy after PCI in AF — reduced clinically significant bleeding.

2016

RE-DUAL PCI

Dabigatran + P2Y12 inhibitor vs warfarin triple therapy after PCI in AF — less bleeding, non-inferior thromboembolism.

2017

MANAGE

Dabigatran in perioperative MI/myocardial injury after non-cardiac surgery — reduced major vascular complications.

2018

MATRIX

MATRIX 1-year results: radial access lowered net adverse clinical events vs femoral in invasively managed ACS; bivalirudin did not beat unfractionated heparin.

2018

RIVAL

Radial vs femoral access in ACS undergoing angiography — no overall difference; less major bleeding with radial.

2011

EVERESTII

MitraClip vs surgery for significant MR — less effective at MR reduction but safer with similar functional benefits.

2011

RECOVERY

Early SAVR vs watchful waiting in asymptomatic very severe AS — reduced operative/CV death.

2020

AVATAR

Early SAVR vs conservative care in asymptomatic severe AS — reduced composite of mortality and CV events.

2021

EARLY-TAVR

Early TAVR vs clinical surveillance in asymptomatic severe AS — reduced death/stroke/unplanned hospitalization.

2024

SURTAVI

Self-expanding TAVR vs SAVR in intermediate risk aortic stenosis — non-inferior all-cause death/stroke.

2017

DAPA-MI

Dapagliflozin vs placebo in MI without prior diabetes/HF — improved cardiometabolic outcomes; no MACE difference.

2023

EMPACT-MI

Empagliflozin vs placebo after acute MI with HF risk factors — no reduction in HF hospitalization or death.

2024

CANTOS

Canakinumab (anti-IL-1β) in post-MI with elevated hsCRP — reduced recurrent CV events independent of lipids.

2017

TIMACS

Routine early (<24h) vs delayed intervention in non-ST ACS — early benefit limited to high-risk subgroup.

2009

RITA-3

Early invasive vs conservative strategy in non-ST ACS — reduced refractory angina and MI long-term.

2002

ISCHEMIA-CKD

Invasive vs conservative strategy in stable CAD with advanced CKD — no reduction in death or MI.

2020

BARI 2D

Revascularization vs medical therapy in T2DM with stable CAD — overall no survival difference; CABG better in three-vessel.

2009

SYNTAX

PCI vs CABG in three-vessel/left main CAD — CABG better for complex anatomy at 1 year.

2009

COMPLETE

Complete vs culprit-only revascularization in STEMI multivessel disease — reduced CV death/MI.

2019

DANAMI-3-PRIMULTI

FFR-guided complete revascularization vs culprit-only in STEMI multivessel disease — reduced repeat revascularization.

2015

ECLS-SHOCK

VA-ECMO vs control in MI with cardiogenic shock — no mortality benefit, more bleeding/vascular complications.

2023

IABP-SHOCK II

IABP vs control in MI cardiogenic shock with planned revascularization — no 30-day mortality reduction.

2012

REVEAL

Anacetrapib added to statin in vascular disease — modest reduction in major coronary events.

2017

AFCAPS/TexCAPS

Lovastatin in low-LDL adults without CAD — reduced first acute coronary events.

1998

VALOR-HCM

Mavacamten in patients with obstructive HCM eligible for septal reduction — reduced need for surgery/ablation.

2022

SHOCK

Early revascularization vs initial medical stabilization in MI cardiogenic shock — improved 6-month mortality.

1999

CULPRIT-SHOCK

Culprit-lesion-only vs multivessel PCI in cardiogenic shock — culprit-only reduced 30-day death/renal failure.

2017

HOST-EXAM

Clopidogrel vs aspirin monotherapy beyond DAPT period after PCI — clopidogrel reduced CV and bleeding events.

2021

MASTER-DAPT

1-month vs ≥3-month DAPT in high bleeding risk patients after PCI — non-inferior, less bleeding.

2021

STOPDAPT-2

1-month DAPT then clopidogrel monotherapy vs 12-month DAPT after PCI — fewer CV/bleeding events.

2019

TWILIGHT

Ticagrelor monotherapy vs ticagrelor+aspirin after 3 months PCI in high-risk patients — reduced bleeding without ischemic penalty.

2019

TRITON-TIMI 38

Prasugrel vs clopidogrel in ACS undergoing PCI — reduced ischemic events, more bleeding.

2007

PLATO

Ticagrelor vs clopidogrel in ACS — reduced CV death/MI/stroke, slightly more non-CABG bleeding.

2009

GUSTO-I

Accelerated tPA vs streptokinase in acute MI — tPA reduced 30-day mortality with slightly more strokes.

1993

ISIS-2

Streptokinase and aspirin in suspected acute MI — each independently reduced mortality, additive benefit.

1988

ATLAS ACS 2-TIMI 51

Low-dose rivaroxaban added to antiplatelet therapy after ACS — reduced CV events, more bleeding.

2012

ACTIVE-W

Clopidogrel + aspirin vs warfarin in AF — warfarin superior in preventing vascular events.

2006

ACTIVE-A

Aspirin + clopidogrel vs aspirin alone in AF unsuitable for warfarin — reduced stroke, more bleeding.

2009

EARLY-AF

Cryoablation vs antiarrhythmic drugs as initial therapy in paroxysmal AF — reduced atrial tachyarrhythmias.

2021

STOP-AF

Cryoablation as first-line therapy vs antiarrhythmic drugs in paroxysmal AF — reduced AF recurrence.

2021

PRAGUE-17

LAA occlusion vs DOAC in high-risk AF — non-inferior composite of CV events and bleeding.

2020

PREVAIL

Watchman LAA closure vs warfarin in non-valvular AF — improved procedural safety, mixed efficacy endpoints.

2014

PROTECT-AF

Watchman LAA closure vs warfarin in non-valvular AF — non-inferior for stroke, more procedural events early.

2009

ATHENA

Dronedarone vs placebo in AF/AFL with CV risk — reduced first CV hospitalization or death.

2009

RACE

Rate vs rhythm control in persistent AF — non-inferior outcomes with rate control strategy.

2002

AFFIRM

Rhythm vs rate control in older atrial fibrillation patients — no survival difference, similar outcomes.

2002

PROMINENT

Pemafibrate vs placebo in T2DM with hypertriglyceridemia — no reduction in major CV events.

2022

STRENGTH

Omega-3 carboxylic acids vs corn oil in high CV risk — no reduction in CV events, stopped early for futility.

2020

ORION-11

Inclisiran in ASCVD or risk equivalents — significant durable LDL-C lowering with twice-yearly injections.

2020

ORION-10

Inclisiran (siRNA against PCSK9) in ASCVD — sustained LDL reduction with twice-yearly dosing.

2020

AIM-HIGH

Extended-release niacin added to simvastatin in low HDL CAD — no incremental CV benefit, stopped early.

2011

HPS2-THRIVE

Niacin/laropiprant added to statin — no reduction in major vascular events, more adverse effects.

2014

HPS

Simvastatin in high-risk patients regardless of baseline LDL — reduced mortality and vascular events.

2002

TNT

Atorvastatin 80mg vs 10mg in stable CAD — high-dose reduced major CV events.

2005

PROVE IT-TIMI 22

High-dose atorvastatin vs moderate pravastatin in ACS — intensive statin reduced CV events.

2004

WOSCOPS

Pravastatin in men with hypercholesterolemia but no MI — reduced CV events in primary prevention.

1995

RADIANCE-HTN

Ultrasound renal denervation vs sham in uncontrolled hypertension — modest BP reduction at 2 months.

2018

VALUE

Valsartan vs amlodipine in high-risk hypertension — similar primary CV outcomes, amlodipine lowered BP more.

2004

INVEST

Verapamil-based vs atenolol-based therapy in hypertensive CAD — similar primary CV outcomes.

2003

PATHWAY-2

Spironolactone vs bisoprolol vs doxazosin in resistant hypertension — spironolactone most effective.

2015

SYMPLICITY HTN-3

Renal denervation vs sham in treatment-resistant hypertension — no significant BP reduction at 6 months.

2014

ACCOMPLISH

Benazepril/amlodipine vs benazepril/HCTZ in high-risk hypertension — reduced CV events with amlodipine combo.

2008

ASCOT-BPLA

Amlodipine-based vs atenolol-based regimen in hypertension — reduced CV events and all-cause mortality.

2005

LIFE

Losartan vs atenolol in hypertension with LVH — reduced composite CV endpoint, mainly driven by stroke.

2002

HYVET

Indapamide ± perindopril in patients ≥80 years with hypertension — reduced stroke and all-cause mortality.

2008

ATTR-ACT

Tafamidis in ATTR cardiomyopathy — reduced all-cause mortality and CV hospitalization vs placebo.

2018

EXPLORER-HCM

Mavacamten vs placebo in symptomatic obstructive HCM — improved exercise capacity and LVOT gradient.

2020

CHAMPION

Implantable hemodynamic monitor (CardioMEMS) in NYHA III HF — reduced HF hospitalizations.

2011

DANISH

Prophylactic ICD in non-ischemic systolic HF — no significant all-cause mortality reduction.

2016

RAFT

CRT-D vs ICD in NYHA II-III HF with wide QRS — reduced death and HF hospitalization.

2010

MADIT-CRT

CRT-D in mild HF (NYHA I-II) with EF ≤30% and wide QRS — reduced HF events vs ICD alone.

2009

CARE-HF

CRT-P vs medical therapy in HFrEF with wide QRS — reduced mortality and HF hospitalization.

2005

COMPANION

CRT-P and CRT-D vs medical therapy in advanced HF with wide QRS — reduced hospitalization/death.

2004

MADIT-II

Prophylactic ICD in post-MI patients with EF ≤30% — reduced all-cause mortality vs conventional therapy.

2002

SCD-HeFT

ICD vs amiodarone vs placebo in HFrEF (ischemic and non-ischemic) — ICD reduced all-cause mortality.

2005

AIRE

Ramipril in post-MI patients with HF — reduced all-cause mortality vs placebo.

1993

SAVE

Captopril post-MI in asymptomatic LV dysfunction — reduced mortality and progression to HF.

1992

I-PRESERVE

Irbesartan vs placebo in HFpEF — no significant reduction in death or CV hospitalization.

2008

CHARM-Alternative

Candesartan in ACE inhibitor-intolerant HFrEF — reduced CV death/HF hospitalization vs placebo.

2003

Val-HeFT

Valsartan added to standard therapy in HFrEF — reduced combined endpoint of mortality/morbidity.

2001

CONSENSUS

Enalapril vs placebo in NYHA IV HF — first trial to show ACE inhibitor mortality benefit, stopped early.

1987

SOLVD

Enalapril vs placebo in HFrEF with reduced ejection fraction — reduced mortality and HF hospitalization.

1991

COPERNICUS

Carvedilol in severe HFrEF — reduced all-cause mortality, expanded beta-blocker use to severe HF.

2001

CIBIS-II

Bisoprolol vs placebo in moderate-severe HFrEF — reduced all-cause mortality, stopped early for benefit.

1999

MERIT-HF

Metoprolol CR/XL in chronic HFrEF — reduced all-cause mortality, established beta-blocker benefit in HF.

1999

EPHESUS

Eplerenone in post-MI patients with LV dysfunction and HF — reduced all-cause mortality and CV events.

2003

RALES

Spironolactone added to standard therapy in severe HFrEF — reduced mortality, stopped early for benefit.

1999

TOPCAT

Spironolactone vs placebo in HFpEF — no significant reduction in primary composite, regional heterogeneity raised efficacy questions.

2014

ProCESS

Protocolized early goal-directed therapy in sepsis — no mortality benefit vs usual care.

2014

SUSTAIN-6

Semaglutide (GLP-1) in T2DM with high CV risk — significant reduction in major CV events.

2016

ATTAIN-MAINTAIN

Abstract Incretins have improved the management of obesity and its related complications, but maintaining these health benefits requires ongoing administration, which can be challenging.

2026

SURMOUNT-MAINTAIN

Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial

2026

DCCT

Intensive vs conventional glycemic control in T1DM — major reduction in microvascular complications.

1993

CAST

Encainide/flecainide vs placebo to suppress PVCs post-MI — increased mortality; pivotal negative trial.

1991

WHI (E+P)

Hormone replacement (estrogen + progestin) in postmenopausal women — increased breast cancer and CVD; stopped early.

2002

ARRIVE

Elective induction at 39 weeks vs expectant management in low-risk nulliparous women — fewer cesareans without harm.

2018

ASCEND

Pirfenidone in IPF (confirmatory trial) — slowed decline, reduced mortality.

2014

INPULSIS-1

Nintedanib in IPF — slowed FVC decline.

2014

CAPACITY

Pirfenidone in idiopathic pulmonary fibrosis — slowed lung function decline.

2011

ANDROMEDA-SHOCK

Capillary refill vs lactate-guided resuscitation in septic shock — trend toward lower mortality with CRT-guided care.

2019

CESAR

ECMO referral in severe respiratory failure — improved 6-month outcomes.

2009

ARMA (ARDSNet)

Low tidal volume ventilation (6 mL/kg) in ARDS — reduced mortality; defined modern ventilator strategy.

2000

NETTER-1

177Lu-DOTATATE PRRT in advanced midgut neuroendocrine tumors — established peptide receptor radionuclide therapy.

2017

EMBRACA

Talazoparib (PARP inhibitor) in BRCA+ metastatic breast cancer — improved PFS vs chemotherapy.

2018

KATHERINE

T-DM1 vs trastuzumab in residual HER2+ breast cancer after neoadjuvant therapy — major iDFS benefit.

2019

APHINITY

Adjuvant pertuzumab + trastuzumab + chemo in HER2+ early breast cancer — modest invasive DFS benefit.

2017

CLEOPATRA

Pertuzumab + trastuzumab + docetaxel in first-line HER2+ metastatic breast cancer — longer PFS; the survival benefit was reported in 2015.

2012

IMpassion130

Atezolizumab + nab-paclitaxel in PD-L1+ TNBC — PFS benefit (controversial OS).

2018

PACIFIC

Durvalumab consolidation after chemoradiation in unresectable stage III NSCLC — markedly longer PFS; OS reported later.

2017

FLAURA

First-line osimertinib vs first-generation EGFR-TKIs in EGFR-mutant NSCLC — longer PFS (18.9 vs 10.2 months); OS immature at this analysis.

2017

CheckMate-067

Nivolumab + ipilimumab or nivolumab alone vs ipilimumab in untreated advanced melanoma — longer progression-free survival; OS data immature.

2015

KEYNOTE-407

First-line pembrolizumab + chemo in squamous NSCLC — improved overall survival.

2018

KEYNOTE-189

First-line pembrolizumab + chemo in non-squamous NSCLC — significant OS and PFS gain.

2018

KEYNOTE-024

First-line pembrolizumab vs chemotherapy in PD-L1-high NSCLC — major overall survival benefit.

2016

ASPREE

Low-dose aspirin in healthy elderly primary prevention — no benefit, increased bleeding.

2018

mRNA-1273

Moderna mRNA COVID-19 vaccine Phase 3 — 94% efficacy.

2020

BNT162b2

Pfizer-BioNTech mRNA COVID-19 vaccine Phase 3 — 95% efficacy.

2020

SOLIDARITY

WHO multi-drug COVID-19 treatment trial — remdesivir, HCQ, lopinavir, and IFN-β not effective on mortality.

2020

ACTT-1

Remdesivir in hospitalized COVID-19 — shorter time to recovery; modest mortality signal.

2020

WAKE-UP

IV alteplase in wake-up stroke with DWI-FLAIR mismatch — extended thrombolysis to unknown-onset stroke.

2018

EXTEND

IV alteplase 4.5-9 hours with perfusion imaging selection — improved functional outcomes.

2019

DEFUSE-3

Thrombectomy 6-16 hours in large-vessel occlusion with perfusion mismatch — major outcome improvement.

2018

DAWN

Thrombectomy 6-24 hours from last-known-normal with imaging mismatch — substantial functional benefit.

2017

NINDS

IV alteplase within 3 hours of stroke onset — established acute thrombolysis as standard of care.

1995

UKPDS

Intensive vs conventional glycemic control in newly diagnosed T2DM — reduced microvascular complications.

1998

STEP-HFpEF

Semaglutide in obesity-related HFpEF — improved symptoms, weight, and inflammation.

2023

STEP 1

Once-weekly semaglutide 2.4 mg in obesity — ~15% weight loss vs placebo.

2021

FLOW

Semaglutide in T2DM with chronic kidney disease — reduced renal and CV events.

2024

SELECT

Semaglutide in non-diabetic overweight/obese patients with CVD — reduced major CV events.

2023

DAPA-CKD

Dapagliflozin in CKD regardless of diabetes — broad renal, CV, and mortality benefit.

2020

CREDENCE

Canagliflozin in T2DM + diabetic kidney disease — major reduction in renal and CV endpoints.

2019

CANVAS

Canagliflozin in T2DM with CV risk — CV event benefit but signal for amputations and fractures.

2017

DECLARE-TIMI 58

Dapagliflozin in T2DM with or at risk for CVD — reduced HF hospitalization and renal endpoints.

2018

LEADER

Liraglutide (GLP-1) in T2DM with high CV risk — reduced CV death and all-cause mortality.

2016

EMPA-REG OUTCOME

Empagliflozin in T2DM with established CVD — first SGLT2i to reduce CV death; class-defining trial.

2015

AUGUSTUS

Antithrombotic strategies in AF + ACS/PCI — apixaban without aspirin reduced bleeding without raising ischemic events.

2019

POISE-2

Perioperative aspirin and clonidine in non-cardiac surgery — neither reduced CV events; aspirin increased bleeding.

2014

POISE

Perioperative metoprolol in non-cardiac surgery — fewer MIs but more strokes and total deaths.

2008

COAPT

MitraClip + GDMT vs GDMT alone in HF with severe secondary MR — reduced HF hospitalization and mortality.

2018

Evolut Low Risk

Self-expanding TAVR vs surgical AVR in low-surgical-risk AS — non-inferior 24-month outcomes.

2019

PARTNER 3

TAVR vs surgical AVR in low-risk severe AS — superior 1-year outcomes with TAVR.

2019

PARTNER 2A

TAVR vs surgical AVR in intermediate-risk severe AS — non-inferior outcomes, expanded TAVR indications.

2016

PARTNER 1A

TAVR vs surgical AVR in high-surgical-risk severe AS — non-inferior 1-year mortality, paradigm shift.

2011

PEGASUS-TIMI 54

Long-term ticagrelor added to aspirin 1-3 years post-MI — reduced CV events at cost of bleeding.

2015

ISAR-REACT 5

Prasugrel vs ticagrelor in ACS — prasugrel reduced primary composite of death, MI, or stroke.

2019

FAME 2

FFR-guided PCI + OMT vs OMT alone in stable CAD — lower urgent revascularization with PCI.

2012

FAME

FFR-guided PCI vs angiography-guided PCI in multivessel CAD — fewer adverse events with FFR guidance.

2009

NOBLE

PCI vs CABG in left main CAD — CABG superior on composite endpoint.

2016

EXCEL

PCI (everolimus-eluting stents) vs CABG in left main CAD with low-intermediate SYNTAX score — noninferior for death, stroke or MI at 3 years.

2016

FREEDOM

CABG vs PCI in diabetes with multivessel CAD — CABG reduced major CV events and mortality.

2012

ORBITA-2

PCI vs sham in stable angina off antianginal medications — significant placebo-controlled angina relief from PCI.

2023

COURAGE

PCI + OMT vs OMT alone in stable CAD — no mortality benefit from initial PCI, similar MI rates.

2007

AVERROES

Apixaban vs aspirin in AF patients unsuitable for warfarin — major stroke reduction with similar bleeding.

2011

CASTLE-AF

Catheter ablation vs medical management in AF + HFrEF — lower mortality and HF hospitalization with ablation.

2018

EAST-AFNET 4

Early rhythm control vs usual care in early AF — fewer adverse cardiovascular outcomes.

2020

CABANA

Catheter ablation vs antiarrhythmic drugs in AF — no significant difference in primary composite (ITT analysis).

2019

ARISTOTLE

Apixaban vs warfarin in nonvalvular AF — superior stroke prevention, less bleeding, and mortality benefit.

2011

ROCKET-AF

Rivaroxaban vs warfarin in nonvalvular AF — non-inferior for stroke prevention with similar major bleeding.

2011

RE-LY

Dabigatran 110/150 mg vs warfarin in nonvalvular AF — first DOAC to demonstrate stroke prevention with less hemorrhage.

2009

4S

Simvastatin vs placebo in established CHD with hypercholesterolemia — first trial to show statins reduce mortality.

1994

CLEAR Outcomes

Bempedoic acid in statin-intolerant patients — modest reduction in major CV events.

2023

REDUCE-IT

Icosapent ethyl (high-dose EPA) in statin-treated patients with elevated triglycerides — significant CV event reduction.

2019

ODYSSEY OUTCOMES

Alirocumab (PCSK9) in post-ACS — reduced major CV events with mortality signal in higher-LDL subgroup.

2018

FOURIER

Evolocumab (PCSK9 inhibitor) added to statin in atherosclerotic disease — large LDL drop, modest event reduction.

2017

IMPROVE-IT

Ezetimibe + simvastatin vs simvastatin alone in post-ACS — added LDL lowering yielded modest event reduction.

2015

ALLHAT

First-line thiazide vs ACE inhibitor vs CCB in hypertension — chlorthalidone non-inferior or superior at lower cost.

2002

STEP (BP)

Intensive (<130) vs standard (<150) SBP in elderly Chinese adults — fewer CV events with intensive control.

2021

HOPE-3

Rosuvastatin + candesartan/HCTZ in intermediate-risk primary prevention — statin reduced events; BP combo only helped if hypertensive.

2016

EMPHASIS-HF

Eplerenone in mild HFrEF (NYHA II) — extended MRA benefit to less severe heart failure.

2011

SHIFT

Ivabradine in HFrEF with HR ≥70 on beta-blocker — reduced HF hospitalization and improved symptoms.

2010

CHARM-Added

Candesartan added to ACE inhibitor in HFrEF — modestly reduced CV death and HF hospitalization.

2003

FINEARTS-HF

Finerenone (non-steroidal MRA) in HFmrEF/HFpEF — reduced CV death and HF events.

2024

STRONG-HF

High-intensity rapid up-titration of GDMT after acute HF — fewer readmissions and lower mortality.

2022

VICTORIA

Vericiguat (soluble guanylate cyclase stimulator) in recent-decompensation HFrEF — reduced CV death and HF hospitalization.

2020

GALACTIC-HF

Omecamtiv mecarbil (cardiac myosin activator) in HFrEF — modest reduction in HF events, no mortality signal.

2021

PIONEER-HF

Sacubitril/valsartan initiated in-hospital after acute HF — faster NT-proBNP reduction vs enalapril.

2019

DELIVER

Dapagliflozin in HFpEF (LVEF >40%) — extended SGLT2i benefit across the EF spectrum.

2022

EMPEROR-Preserved

Empagliflozin in HFpEF — first SGLT2i shown to reduce HF hospitalization regardless of ejection fraction.

2021

ONTARGET

Telmisartan vs ramipril vs combo in high-CV-risk patients — non-inferior, combo gave no benefit and more adverse events.

2008

STICH

CABG + medical therapy vs medical therapy alone in ischemic cardiomyopathy — no significant reduction in all-cause death at 5 years; fewer CV deaths and hospitalizations.

2011

RECOVERY

Dexamethasone in hospitalized COVID-19 — first proven mortality-reducing therapy in COVID-19.

2021

ACCORD-BP

Intensive (<120) vs standard (<140) BP control in T2DM — no reduction in primary composite, more adverse events.

2010

ISCHEMIA

Routine invasive vs optimal medical therapy in stable CAD with moderate ischemia — no mortality benefit from invasive approach.

2020

PARADIGM-HF

Sacubitril/valsartan vs enalapril in HFrEF — established ARNI as superior to ACE inhibitor.

2014

EMPEROR-Reduced

Empagliflozin in HFrEF — confirmed SGLT2i class benefit, reduced HF hospitalization and CV death.

2020

DAPA-HF

Dapagliflozin (SGLT2i) added to GDMT in HFrEF — first SGLT2i to show benefit regardless of diabetes status.

2019

SPRINT

Intensive (<120) vs standard (<140) BP control in non-diabetic high-CV-risk adults — fewer CV events and deaths.

2015

JUPITER

Rosuvastatin in primary prevention with elevated hs-CRP and normal LDL — large CV event reduction; stopped early for benefit.

2008

ENGAGE AF-TIMI 48

Edoxaban 30/60 mg vs warfarin in AF — non-inferior efficacy with less hemorrhagic stroke.

2013

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