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FDA advisors were nearly unanimous in backing the TriClip G4 transcatheter edge-to-edge repair (TEER) device as a treatment for severe tricuspid regurgitation (TR).

During an advisory committee meeting on Tuesday, the FDA's Circulatory System Devices Panel voted 13-1 that the benefits of the TriClip outweigh the risks when used for intermediate-or-higher-risk patients with severe TR who have symptoms despite optimal medical therapy.

Evidence that the TriClip reduced TR without excess safety events and significantly improved the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall score, a patient-reported quality-of-life metric, was enough for the majority of Tuesday's panelists to vote yes to both the device's effectiveness (12-2) and safety (14-0).

"The safety data speaks for itself. The device performs very well," said surgeon David Yuh, MD, of Stamford Hospital in Connecticut, who called TriClip a "significant advance" for the treatment of right heart failure.

"If we can help symptoms at a low cost in terms of risk, it makes a lot of sense," said James Blankenship, MD, an interventional cardiologist at the University of New Mexico in Albuquerque. He noted that the safety profile of the TriClip TEER seems better than many established procedures, including hip replacement.

Committee members generally agreed while acknowledging that the TRILUMINATE trial, the basis of TriClip's premarket application, technically met the superiority composite endpoint without being able to prove that the device helps hard outcomes any better than medical therapy alone.

In that open-label pivotal trial, TriClip recipients showed improved health status for patients on Bayesian analysis (win ratio 1.44, 95% CI 1.03-2.08). The only individual component of this primary endpoint to significantly favor the device was the KCCQ (≥15-point improvement achieved by 50% vs 26% of patients) -- with no reduction in mortality or heart failure hospitalization per se.

"In terms of efficacy, what the patient is experiencing, I do put a lot of faith in the KCCQ data even though [there are concerns about] the placebo effect," Yuh said. "It's still the reality to the patient, and to discount that does a disservice to the patient."

As for safety in TRILUMINATE, there were numerically more deaths, tricuspid valve interventions, and bleeding events associated with the TriClip intervention. Being that the small differences did not reach statistical significance, however, no one on Tuesday's panel expressed concerns about major adverse events occurring in patients.

FDA advisory committee members did take issue with the finding that TriClip's benefits in the trial did not extend to participating sites enrolling fewer than 10 patients, suggesting a steep learning curve precluding broad adoption for operators.

Notably, Abbott had taken the design for the TriClip from the MitraClip, now considered a mature technology for treating primary and secondary mitral regurgitation. Curiously, data suggest that more experience with the MitraClip did not appear to correlate with better TriClip outcomes in lower-enrolling centers.

TR occurs when the tricuspid valve leaflets do not close completely during systole, causing blood to regurgitate from the right ventricle into the right atrium. Affected patients have few treatment options, and surgery is often high-risk due to a typically older, sicker patient profile.

Abbott is proposing that TriClip be indicated for improvement of "health status" in patients with severe TR that is symptomatic despite optimal medical therapy and who are at intermediate or greater risk for surgery and deemed appropriate TEER candidates by a heart team.

"I think it's important to consider the alternatives for these patients, and the alternatives are limited," said Bradley Bart, MD, of the University of Minnesota and Minneapolis VA Medical Center.

That may change in the near future as many transcatheter therapies are currently being developed for TR.

In fact, the FDA just approved the Evoque tricuspid valve replacement system by Edwards Lifesciences, while that company's Pascal repair system has its pivotal trial scheduled for completion at the end of this year.

Abbott said it has a continued access protocol that will follow several hundred TriClip patients for 5 years after the procedure. The device maker is also proposing postmarket surveillance of the TriClip device through the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry should the device be FDA approved.

Panelist Marc Katz, MD, MPH, of the Medical University of South Carolina in Charleston, said he had concerns about indication creep in the real world resulting in sicker, non-TRILUMINATE-like patients getting the device. "That's not going to help results overall, especially as less experienced teams get involved."

He said he voted no to TriClip's efficacy but ultimately "caved" and voted yes for the benefit-risk question based on his personal experience on putting MitraClips in the tricuspid position. "There is a role for it in a limited population. It's going to have to find its niche between valves and leaflet modification."

The sole "no" vote for benefit-risk came from Paul Hauptman, MD, of the University of Nevada in Reno, who expressed the "need to pull back on unbridled enthusiasm" for the TriClip. He cautioned that important questions remain, including a better definition of which patients are likely to benefit.

He encouraged the FDA to look critically at data from the continued access protocol at 1 year. He also suggested more work to evaluate post-implant deployment of defibrillator leads and pacemaker leads in TriClip recipients and what happens a few years later when patients need their leads revised.

The FDA is not required to follow the advice of its advisory committees, but it often does.

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