FDA panel recommends ultrasound renal denervation device for uncontrolled hypertension
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Key takeaways:
- An FDA panel voted that for adults with uncontrolled hypertension, the benefits of an ultrasound renal denervation device outweigh its risks.
- Concerns about long-term durability of effect were expressed.
An FDA advisory panel voted 10-2 that the benefits of an ultrasound renal denervation system outweigh the risk for use in adults with uncontrolled hypertension who are unresponsive or intolerant to antihypertensive medications.
In a meeting of the FDA’s Circulatory System Devices Panel of the Medical Devices Advisory Committee Meeting, members also voted 8-3, with one abstention, that the Paradise ultrasound renal denervation system (ReCor) is effective for use in patients with uncontrolled hypertension, and voted unanimously (12-0) that the device is safe for use.
The system is indicated to reduce BP by ablating the nerves surrounding the renal artery in adult patients with uncontrolled hypertension, “who may be inadequately responsive to, or who are intolerant to, antihypertensive medications.” During the meeting, some panelists expressed concerns that renal denervation is not superior to antihypertensive medications and that, while studies demonstrated an acute decrease in BP with the procedure, the decrease was modest and any long-term durability remains unclear.
‘A novel mechanism’
“I voted ‘yes’ on efficacy with some misgivings, based on the small effect size and the heterogeneity of the response,” John Hirshfeld, Jr., MD, emeritus professor of medicine at the University of Pennsylvania Perelman School of Medicine, said after the vote. “I voted ‘yes’ because, since this is a novel mechanism for treating hypertension, [renal denervation] is an important tool to have in the toolbox. Hopefully, once in the toolbox, it will be used responsibly by the clinical community and promoted responsibly by the sponsor.”
Panels also debated the proposed indication for ultrasound renal denervation, noting that words such as “inadequately responsive,” “intolerant” and “uncontrolled hypertension” were not clearly defined.
“I voted ‘yes’ for safety. I voted ‘no’ for both the efficacy and the risk/safety profile primarily because I did not feel comfortable voting ‘yes’ based on the precise wording of the indication,” Benjamin Saville, PhD, director and senior statistical scientist at Berry Consultants in Austin, Texas, said after the vote. “Based on all of the feedback from my clinical colleagues [about] that indication, the indication was my main concern. There is clearly a benefit in the study population ... that benefit demonstrated is more short-term. It is unknown what longer benefit we might have.”
Keith Allen, MD, director of surgical research at St. Luke’s Hospital of Kansas City, Missouri, also expressed concerns about durability of effect with renal denervation.
“I voted ‘no’ on risk/benefit, despite this being a breakthrough device, because I have real concerns based on how it is currently listed and how it would be used in the real world,” Allen said after voting.
As Healio previously reported, ReCor conducted three independent clinical studies —RADIANCE-HTN SOLO and RADIANCE-HTN TRIO and the pivotal study, RADIANCE-II — evaluating the renal denervation system in patients with uncontrolled hypertension. All three trials were randomized, double-blind and sham-controlled. In SOLO and RADIANCE-II, participants were taken off antihypertensive medications 4 weeks prior to randomization; in TRIO, participants received a standardized hypertension medication regimen (triple pill) 4 weeks before randomization. For all three trials, the primary safety endpoint was a composite of major adverse events and the primary effectiveness endpoint was the difference between the treatment and sham groups in baseline-adjusted reduction in daytime ambulatory systolic BP (ASBP) at 2 months after the procedure. The ultrasound renal denervation system received an FDA breakthrough device designation in December 2020.
In RADIANCE-II, at 2 months, daytime ambulatory systolic BP declined 7.9 mm Hg in the renal denervation group and 1.8 mm Hg in the sham group, for a between-group difference in means of –6.3 mm Hg (95% CI, –9.3 to –3.2; P < .0001). Those results were consistent with the findings in SOLO and TRIO, confirming that ultrasound renal denervation lowers BP across the spectrum of hypertension, according to ReCor. The 2018 Circulatory System Devices Panel recommended a 5-7 mm Hg relative BP reduction in renal denervation-treated patients vs. controls as a clinically meaningful threshold for effectiveness, according to the FDA.
According to studies, no patients required renal artery intervention and no renal artery narrowing was considered clinically significant.
“Renal arterial imaging showed no cases of > 70% renal artery diameter stenosis through 12 months,” the FDA noted in background briefing documents. “However, there was a 0.8% incidence of 51-70% diameter stenosis, a 2.1% incidence of 31-50% diameter stenosis, and a 1.3% incidence of 1-30% diameter stenosis. Although mild to moderate luminal narrowing is not associated with a functional reduction in renal blood flow, long-term follow-up data are limited, and renal arterial lesions may progress over time.”
Discussing the safety and efficacy of ultrasound renal denervation, Saville noted that there are no safety concerns, but also “low benefit” demonstrated.
“There are certainly no safety concerns; this is low risk, but it is also low benefit,” Saville said. “There is a stronger benefit in the short-term. The question, to me, is how important is durability; that we have a long-term benefit? It is not an easy decision. It comes down to what is important: Timely access to something that will provide some short-term benefit in the hopes that there will be a longer long-term benefit.”
ReCor noted that the studies were not designed to answer questions of long-term durability.
‘A critical gap in care’
Speaking on behalf of ReCor, Naomi D.L. Fisher, MD, director of hypertension services and the hypertension specialty clinic at Brigham and Women’s Hospital, said that up to half of patients prescribed medications for hypertension are not taking them, adding that, for many people, lifestyle modification and standard care medical therapies are inadequate.
“The reality is that many people do not take, or cannot tolerate, enough antihypertensive medications for a host of reasons to control their BP,” Fisher said. “For these patients also, ultrasound renal denervation could fill a critical gap in care. The benefits of ultrasound renal denervation far outweigh the risks. Risks are minimal, especially in light of the substantial benefits we observed.
“Access to renal denervation as a supplement to medical therapy would be a significant medical advance,” Fisher said.
Panelists agreed that any postapproval study should include a detailed analysis of patient antihypertensive medications and doses used before and after ultrasound renal denervation, careful ambulatory BP monitoring and more data on patients across age groups and races. During a Q&A session after the ReCor presentation, the company said any postapproval study will seek to actively enroll patients from underrepresented groups, who were not as well represented as white participants in the three trials.
The FDA is not required to follow the recommendations of its advisory panels, but it usually does.
References:
- FDA briefing documents. Available at: http://www.fda.gov/media/171388/download. Accessed Aug. 22, 2023.
- ReCor briefing documents. Available at http://www.fda.gov/media/171397/download. Accessed Aug. 22, 2023.
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FDA. Circulatory System Devices Panel of the Medical Devices Advisory Committee (MDAC) Live Video. Presented Aug. 22, 2023. Accessed Aug. 22, 2023.
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