The Lancet June 09, 2018

Endovascular ultrasound renal denervation to treat hypertension (RADIANCE-HTN SOLO): a multicentre, international, single-blind, randomised, sham-controlled trial

Michel Azizi, Roland E Schmieder, Felix Mahfoud, Michael A Weber, Joost Daemen, Justin Davies, Jan Basile, Ajay J Kirtane, et al.

Source: View publication →

Bottom Line

RADIANCE-HTN SOLO demonstrated that endovascular ultrasound renal denervation significantly reduced daytime ambulatory systolic blood pressure compared to a sham procedure in patients with mild-to-moderate hypertension who were taken off antihypertensive medications.

Key Findings

1. At 2 months, daytime ambulatory systolic blood pressure decreased by 8.5 mm Hg in the ultrasound renal denervation group compared to 2.2 mm Hg in the sham group, resulting in a between-group difference of -6.3 mm Hg (P=0.0001).

2. Daytime ambulatory diastolic blood pressure also significantly decreased with a between-group difference of -2.6 mm Hg (P=0.01).

3. 24-hour ambulatory systolic blood pressure decreased by 7.0 mm Hg in the denervation group versus 3.1 mm Hg in the sham group (a significant difference of -4.1 mm Hg, P=0.006).

4. At 6-month follow-up, after patients were allowed to resume a stepped-care medication protocol, significantly fewer patients in the renal denervation group required antihypertensive medications compared to the sham group (65.2% vs. 84.5%, P=0.008).

5. There were no major adverse events at 30 days in either group, indicating a strong early safety profile for the ultrasound ablation device.

Study Design

Design

RCT

Single-Blind

Sample

146

Patients

Duration

2 mo

Median

Setting

Multicenter, US, Europe

Population Adults aged 18 to 75 years with mild-to-moderate hypertension and daytime ambulatory BP ≥135/85 mm Hg and <170/105 mm Hg after a 4-week washout of up to two antihypertensive medications.

Intervention Endovascular ultrasound renal denervation using the Paradise system.

Comparator Sham procedure consisting of renal angiography only.

Outcome Change in daytime ambulatory systolic blood pressure from baseline to 2 months.

Study Limitations

• The primary efficacy endpoint was assessed at a short follow-up interval of 2 months, which was necessitated for safety reasons to minimize the time patients were kept off antihypertensive medications, limiting assessment of unconfounded long-term durability.

• Operators performing the procedure could not be blinded, rendering the trial technically single-blind (though patients and outcome assessors were masked).

• The sample size (N=146) was sufficiently powered for blood pressure efficacy but was not large enough to detect rare periprocedural or long-term safety events.

• The study enrolled patients with mild-to-moderate hypertension off medications, meaning the immediate findings did not directly apply to patients with resistant hypertension on multiple agents (a population that was subsequently addressed in the RADIANCE-HTN TRIO trial).

Clinical Significance

By rigorously testing endovascular ultrasound renal denervation in the absence of confounding antihypertensive medications and incorporating a sham control arm, RADIANCE-HTN SOLO provided proof-of-principle that the Paradise device exerts a true, biologically significant blood pressure-lowering effect. This reignited confidence in device-based hypertension therapies.

Historical Context

Following the high-profile failure of the sham-controlled SYMPLICITY HTN-3 trial in 2014, the field of renal denervation was practically halted. Researchers hypothesized that HTN-3 was confounded by variable patient medication adherence and incomplete nerve ablation from first-generation, point-by-point radiofrequency catheters. In response, RADIANCE-HTN SOLO utilized a next-generation circumferential ultrasound device (the Paradise system) and a strict off-medication protocol, definitively isolating the physiological effect of renal denervation and proving its fundamental efficacy.

Guided Discussion

High-yield insights from every perspective

Med Student

Medical Student

Based on the pathophysiological mechanism of renal denervation, which specific autonomic pathways are being targeted by the ultrasound energy, and how does their disruption physiologically lower blood pressure in the RADIANCE-HTN SOLO patients?

Key Response

This tests foundational knowledge of the sympathetic nervous system. Renal denervation disrupts both efferent sympathetic nerves (which normally increase renin release, promote sodium retention, and increase renal vascular resistance) and afferent nerves (which send signals to the central nervous system to increase systemic sympathetic tone), thereby reducing overall sympathetic drive and blood pressure.

Resident

The RADIANCE-HTN SOLO trial uniquely required patients to be taken off their antihypertensive medications before the procedure. In standard clinical practice, how does this 'washout' trial design influence how you would select a patient who might benefit from renal denervation today?

Key Response

This question bridges trial design to clinical reality. The trial used an off-medication design to prove physiological efficacy without the major confounder of variable medication adherence. Residents must understand that while the trial proves a biological effect, real-world application currently focuses heavily on resistant hypertension where patients are on multiple drugs, making patient selection a balance between proven biological efficacy and real-world adherence issues.

Fellow

Previous landmark trials like SYMPLICITY HTN-3 failed to show a blood pressure benefit for radiofrequency renal denervation over sham. What specific procedural and anatomical advantages does the endovascular ultrasound technique used in RADIANCE-HTN SOLO offer over the older radiofrequency catheters?

Key Response

This explores interventional nuances. Ultrasound renal denervation delivers uniform, circumferential thermal energy that penetrates deeper into the peri-arterial adventitia compared to the point-by-point, operator-dependent ablation of first-generation radiofrequency catheters. This ensures more complete nerve ablation while sparing the endothelial intima, addressing a major procedural flaw of earlier trials.

Attending

As renal denervation re-emerges as a viable therapy following the RADIANCE-HTN SOLO results, how should we balance the modest absolute reduction in ambulatory daytime systolic blood pressure (roughly 8.5 mmHg) against the cost and invasive nature of the procedure when counseling a non-adherent hypertensive patient?

Key Response

Focuses on clinical wisdom and shared decision-making. An 8.5 mmHg drop is epidemiologically significant for reducing long-term stroke and myocardial infarction risk, roughly equivalent to the effect of 1 to 2 antihypertensive medications. Attendings must weigh this 'always-on' therapy against the realities of lifelong medication non-adherence, procedural risks, and healthcare economics.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD

The RADIANCE-HTN SOLO trial utilized a single-blind, sham-controlled design with a strict medication washout period. What are the methodological trade-offs of using a short-term 2-month primary endpoint in an off-medication population to assess an irreversible device-based intervention?

Key Response

Critiques study design and limitations. A 2-month endpoint minimizes the duration patients remain dangerously off medications and avoids high dropout rates, but it prevents the assessment of long-term durability of the denervation effect and the potential for nerve regeneration, which are critical mechanistic questions for a permanent anatomical intervention.

Journal Editor

During peer review of the RADIANCE-HTN SOLO manuscript, how does the potential for a higher rate of 'escape' medications (re-initiation of antihypertensives prior to the 2-month endpoint due to safety parameters) in the sham arm compared to the denervation arm threaten the validity of the unadjusted ambulatory blood pressure analysis?

Key Response

Looks for statistical confounders and bias. If more sham patients required rescue medications due to dangerously high blood pressure, their final 2-month blood pressure would be artificially lowered by the drugs. This would bias the results toward the null, potentially underestimating the true physiological treatment effect of denervation if the statistical model does not appropriately handle these censored off-medication data points.

Guideline Committee

Current ACC/AHA and ESC/ESH guidelines generally position renal denervation as an experimental procedure or restrict it to clinical trials. Does the RADIANCE-HTN SOLO trial provide sufficient evidence to upgrade its recommendation to an alternative therapy for mild-to-moderate hypertension, or does the reliance on a surrogate endpoint limit its guideline impact?

Key Response

Assesses the threshold for guideline updates. While SOLO provides robust proof-of-concept for efficacy without adherence confounders, guidelines require long-term safety, durability, and hard outcome data (reduction in major adverse cardiovascular events) rather than just surrogate blood pressure markers at 2 months. Therefore, while it represents a breakthrough in evidence, it likely requires supplementary long-term, on-medication outcome data to shift to a Class I or IIa recommendation.

Clinical Landscape

Noteworthy Related Trials

2014

SYMPLICITY HTN-3 Trial

n = 535 · NEJM

Tested

Radiofrequency renal denervation

Population

Patients with severe resistant hypertension

Comparator

Sham procedure

Endpoint

Change in office systolic blood pressure at 6 months

Key result: Renal denervation did not significantly reduce systolic blood pressure compared to a sham control in patients with resistant hypertension.

2020

SPYRAL HTN-OFF MED Pivotal Trial

n = 331 · Lancet

Tested

Radiofrequency renal denervation

Population

Patients with uncontrolled mild-to-moderate hypertension off medications

Comparator

Sham procedure

Endpoint

Change in 24-hour ambulatory systolic blood pressure at 3 months

Key result: Radiofrequency renal denervation significantly reduced both office and ambulatory blood pressure compared with a sham procedure in the absence of antihypertensive medications.

2021

RADIANCE-HTN TRIO Trial

n = 136 · Lancet

Tested

Ultrasound renal denervation

Population

Patients with resistant hypertension on a standardized triple fixed-dose combination pill

Comparator

Sham procedure

Endpoint

Change in daytime ambulatory systolic blood pressure at 2 months

Key result: Ultrasound renal denervation significantly reduced daytime ambulatory systolic blood pressure compared with a sham procedure in patients with resistant hypertension.

Tailored to your role

Want this tailored to you?

Add your specialty or training stage to get role-specific takeaways and more questions.

Personalize this analysis