Amanda Pedersen 1

March 1, 2017

6 Min Read
Debris-Catching Device for TAVR Wins Over FDA Panel

An FDA advisory panel recently recommended approval for Claret Medical's Sentinel Cerebral Protection System based on a lack of alternative options and a low safety risk, but questions remain about the clinical efficacy of the device. As a de novo application, the Sentinel did not require a formal panel vote.

Amanda Pedersen

Claret Medical's Sentinel Cerebral Protection System got a green light from an FDA panel for use during TAVR procedures. The company now expects the device to be on the U.S. market by summer.

Sometimes safety matters more than efficacy, as was the case during a recent FDA advisory panel meeting to discuss a dual-filter device designed to capture and remove debris dislodged during increasingly-popular transcatheter aortic valve replacement (TAVR) procedures.

Learn about hot topics and trends in medical device regulation at ADM Cleveland, March 29-30.

There are embolic protection devices already on the market for carotid and peripheral interventions, but the Sentinel Cerebral Protection System from Santa Rosa, CA-based Claret Medical Inc. is the first device proposed specifically for use during TAVR procedures in order to reduce the incidence and/or impact of embolic events.

James Hallums, senior vice president and international general manager at Claret Medical, told Qmed that up to this point TAVR's key opinion leaders have primarily been interventional cardiologists and cardiac surgeons. "Neurologists have played a realatively small part in terms of what is seen as success in those procedures," he said.

Device makers and physicians have invested a lot of time and energy debating other TAVR issues, like the fact that up to 25% of patients currently end up needing a permanent pacemaker soon after their procedure. But the risk of stroke has always loitered in the background of those conversations, Hallums said. That's beginning to change though, as TAVR indications expand to include younger, lower-risk patient populations.

"Patients say stroke is more of a concern than the risk of dying on the table," Hallums said.

The Sentinel System uses an embrolic filter delivered to the brachiocephalic artery, and a second embrolic filter delivered to the left common carotid artery. At the end of the procedure, the filters and debris are recaptured into the catheter and removed.

FDA asked the advisory panel for input on the device's supporting clinical data, but the panel was not asked to take a formal vote because it was a de novo application. De novo classification means the device is of low or moderate risk and that there is not a substantially equivalent product on the market. Devices that meet de novo criteria are not eligible for 510(k) clearance, but they also are not subject to the same level of scrutiny as a device that goes through the agency's premarket approval process.

In the pivotal trial, dubbed SENTINEL, the stroke rate for Sentinel-protected patients was 5.6% versus 9.1% for unprotected patients. The company noted that the observed peri-procedural stroke rate (within the first 72 hours after the procedure) was reduced by 63%, from 8.2% for unprotected patients to 3.0% for protected patients.

Still, most of the panelists were not convinced that the Sentinel device reduces the risk for stroke or that it improved neurocognitive outcomes, and there was some concern about the relatively small patient number in the randomized pivotal trial (363 patients at 19 U.S. and German centers). Panelists agreed, however, that preventing debris from reaching the brain is a benefit of the Sentinel device, and that preventing some debris from traveling to the brain is better than allowing all of the debris to reach the brain.

Claret's data showed that the device captured and removed embolic debris in 99% of patients in the study, with one in four patients having more than 25 pieces of debris that were large enough to be seen with the naked eye, Hallums said.

FDA also noted in an executive summary that the pivotal trial was not designed to show a reduction in stroke. Rather, it was designed to provide imaging and corroborating clinical evidence that the device reduces ischemic events in the brain as detected by diffusion-weighted MRI.

But the safety results in the context of the TAVR procedure was what ultimately won the panel over.

In the SENTINEL trial, the primary safety endpoint of major adverse cardiovascular and cerebrovascular events (MACCE) at 30 days was met, with reported MACCE in the protected Sentinel group at 7.3%, significantly lower than the pre-specified historical performance goal of 18.3% and the rate of 9.9% seen in the control arm.

Hallums said the positive panel outcome was "validating."

"I was personally surprised by the overwhelming support that came out of the panel hearing," Hallums said. "I'm happy they accepted the totality of the data, they didn't just look at one study in isolation."

A meta-analysis of five randomized controlled clinical trials examining cerebral protection in valve repair and replacement procedures across more than 625 patients was published in the Journal of the American College of Cardiology in January. More than 80% of the patients (510 subjects) came from three of the five cited studies where Claret's dual-filter cerebral protection systems were used. These data demonstrate that the use of cerebral protection is associated with a greater than 40% lower risk of death or stroke after TAVR. According to the company, the data corresponded to a rate of one death or stroke potentially being averted for every 22 patients treated with cerebral protection.

Claret also had the advantage of having a renowned investigator in its corner. Martin Leon, director of the Center for Interventional Vascular Therapy at Columbia University Medical Center and New York Presbyterian Hospital, served as chairman of the SENTINEL clinical steering committee.

 

"The Sentinel device has shown its potential, across multiple trials, to filter and remove braine-borne debris safely, with ver few vascular complications," Leon said. "When we see the size and heterogeneity of the material captured, it is reassuring for me as a practicing TAVR implanter to know that it can be removed from the patient's vasculature before it reaches the brain."

Azin Parhizgar, president and CEO of Claret Medical, said the panel provided valuable feedback that will help the company define future study success criteria in the field of cerebral protection.

Up to this point, Claret has been vague about the projected timeline for getting Sentinel on the U.S. market, but based on the recent panel discussion, Hallums said the company anticipates getting the official FDA green light as early as the second quarter of this year, and "certainly by summer."

Amanda Pedersen is Qmed's news editor. Contact her at [email protected].

[Image credit: Claret Medical Inc.]

Sign up for the QMED & MD+DI Daily newsletter.

You May Also Like