FDA panel recommends TriClip TEER device for severe tricuspid regurgitation
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Key takeaways:
- An FDA panel voted that the benefits of a transcatheter edge-to-edge repair device outweigh risks in severe tricuspid regurgitation.
- Panelists said more data are needed on ideal candidates for the procedure.
An FDA advisory panel voted 13-1 that the benefits of a transcatheter edge-to-edge repair device outweigh any risks in adults with symptomatic severe tricuspid regurgitation, despite no improvement in hard endpoints seen in a pivotal trial.
In a meeting of the FDA’s Circulatory System Devices Panel of the Medical Devices Advisory Committee Meeting, members also voted 12-2 that the TriClip G4 delivery system (Abbott) is effective for patients with severe tricuspid regurgitation who meet the criteria of the proposed label indication and voted unanimously (13-0) that the device is safe for use.
During the meeting, panelists and the FDA noted that the primary outcome of the pivotal TRILUMINATE study — a composite of mortality or tricuspid valve surgery, hospitalization for HF and improvement of at least 15 points in the Kansas City Cardiomyopathy Questionnaire (KCCQ) quality-of-life metric, evaluated at 1 year in a hierarchical fashion— was driven by improvements in KCCQ score without significant reductions in mortality or tricuspid regurgitation grades. Still, panelists agreed that patient-reported outcomes in quality of life were meaningful and that longer-term data may yield more promising mortality results.
“The safety data speaks for itself,” David D. Yuh, MD, FACS, FACC, chair of the department of surgery at Stamford Hospital, said after voting “yes” to all three questions. “The device performed very well, not only in the randomized group but the single-arm study as well. These [data] translated into what I think are meaningful subjective improvements in patient symptomatology. This technology represents a meaningful advance in the treatment of right HF and, as a reformed HF surgeon, I appreciate and sympathize with those who have to deal with right HF. This is a significant advance and although not definitive, it is still a move in the right direction and a lot can be learned from postmarketing studies going forward.”
Severe tricuspid regurgitation is a progressive disease with often debilitating symptoms that impact quality of life, and comes with high operative risk with surgery. Panelists noted that many patients are not responsive to medical therapy.
Abbot’s proposed indication states the TriClip system states the device is intended for “the improvement of health status in patients with symptomatic severe tricuspid regurgitation despite being treated optimally with medical therapy, who are at intermediate or greater risk for surgery and in whom tricuspid valve edge-to-edge repair is appropriate as determined by a heart team.”
Pivotal data; questioning benefit
As Healio previously reported, data from the TRILUMINATE Pivotal trial demonstrated that treatment of severe tricuspid regurgitation with TEER was safe, reduced severity of tricuspid regurgitation and led to improvements in quality of life at 1 year. The trial compared the TriClip G4 delivery system with guideline-directed medical therapy alone in 350 symptomatic patients with severe tricuspid regurgitation. The procedure is performed via the femoral vein and the system utilizes a 25 French delivery catheter to place one or more TriClip devices on the tricuspid valve leaflets to reduce tricuspid regurgitation.
The primary endpoint was met, demonstrating superiority of TEER over medical therapy alone (win ratio = 1.48; 95% CI, 1.06-2.13; P = .02). The demonstration of superiority over medical therapy was driven largely by significant improvements in quality of life. There was no difference between groups in the proportion of patients free from all-cause mortality or tricuspid valve surgery at 1 year and the rate of HF hospitalization at 1 year.
The TRILUMINATE trial will continue to follow patients for 5 years.
While panelists unanimously agreed the device is safe, some expressed skepticism about outcomes after TEER and who might be ideal candidates for the procedure.
“We all agree this is a safe procedure, but I have questions about its overall effectiveness,” Marc R. Katz, MD, MPH, professor and chief of the division of cardiothoracic surgery at Medical University of South Carolina in Charleston, said in a discussion prior to the vote. “It decreased tricuspid regurgitation some and improved KCCQ scores, but other metrics did not change. Medications did not change much. And given that there is now an approved tricuspid valve replacement, once [the valve] is clipped, you take that option off the table in the future. Those are my concerns.”
In background briefing documents, FDA expressed similar concerns, noting that the primary endpoint success in the randomized cohort was driven by improvement in KCCQ score — a patient-reported outcome that could be subject to the placebo effect in an unblinded trial. The agency also noted there was no signal of reduced mortality or HF hospitalization associated with TriClip device implantation through 12 months post-procedure.
“I felt the need to pull back on the unbridled enthusiasm,” Paul J. Hauptman, MD, FHFSA, dean and professor of medicine at the University of Nevada, said after voting “no” on the questions of device effectiveness on whether the benefits of TriClip outweigh any risks. “We have a responsibility to better understand who is going to benefit and that needs better definition. We do not know anything about patients in normal sinus rhythm, at least not in the U.S. study. I still am troubled by the fact that there was no change in diuretics and there was no consistent story with biomarkers. The imaging data are encouraging. So, I ended up being the sole dissenting vote on [question] 3. I encourage the agency to take a critical look at the continued access protocol at 1 year because I suspect those data could tip the scales and shore up what we know from the main cohort.”
Some panelists also questioned how the device might impact any later heart procedures, such as a pacemaker implant, if needed.
“I was very comforted by the data that we reviewed and I do have some shared concerns about the future of what happens when a valve is clipped,” David A. Friedman, MD, FACC, FASE, FASNC, FACP, cardiologist and director of the heart failure program at West Carver Medical Group in Huntington, New York, said after the vote. “How do we pass through a valve? How do we get by with a pulmonary artery catheter? What do electrophysiologists do when implanting a device? These are unanswered questions, and we need more time to discern where these patients go in the future.”
Panelist Craig H. Selzman, MD, professor and chief of the division of cardiothoracic surgery at the University of Utah, agreed, noting that he also had concerns about inappropriate use of the device beyond its label indication.
“When we take the patient population from the average age of our two presidential candidates down to something a little bit lower, that concerns me,” Selzman said during a discussion before the vote. “Once you put this clip on, if there is a surgical option, [the TriClip procedure] takes that away and demands there will be a [valve] replacement. As we think about this, I will state again: Somehow, some way, perhaps in the postmarket studies, as the ‘creep’ goes down to lower ages and patients with less risk, that there be some way to hold the therapy accountable.”
An ‘unmet need’ for tricuspid regurgitation
In a press release issued after the panel’s votes, Lars Søndergaard, MD, chief medical officer and divisional vice president of medical affairs of Abbott's structural heart business, said Abbott “recognized an unmet need” by using its clip-based technology for people with severe tricuspid regurgitation.
“TriClip offers an urgently needed alternative that is safe and effective for people who require tricuspid valve repair but are not able to withstand surgery,” Søndergaard said in the release.
If the FDA approves the device, Abbott said it will initiate a real-world, post-approval study, following patients at 30 days and then annually for 5 years. The TriClip received a CE mark in Europe in 2020.
The FDA is not required to follow the recommendations of its advisory panels, but it usually does.
References:
- FDA briefing documents. Available at: CSDP Feb. 13, 2024 FDA Executive Summary. Accessed Feb 13, 2024.
- Abbott briefing documents. Available at: CSDP Feb. 13, 2024 Sponsor Executive Summary. Accessed Feb. 13, 2024.
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FDA. Circulatory System Devices Panel of the Medical Devices Advisory Committee (MDAC) Live Video. Presented Feb. 13, 2024. Accessed Feb. 13, 2024.
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