FDA Panel Reviews Claret Medical's Sentinel Cerebral Protection System for TAVR
February 27, 2017—Claret Medical Inc. announced that in an open public hearing of the US Food and Drug Administration's Circulatory System Devices Panel held on February 23, virtually all panel members recommended the de novo application of the company's Sentinel cerebral protection system (CPS) be granted, which would enable commercialization of the device in the United States. A formal vote was not taken, as the Sentinel CPS is a medium-risk accessory device reviewed as a de novo application, advised the company.
The Sentinel CPS is designed to protect the brain by capturing and removing debris dislodged during transcatheter aortic valve replacement (TAVR) that would otherwise enter the cerebral circulation and increase the potential for stroke.
According to Claret Medical, the American Association of Neurological Surgeons and the Society of NeuroInterventional Surgery also endorsed the need for embolic protection in TAVR and were represented in the open public hearing by Adnan Siddiqui, MD, Professor of Neurological Surgery at the University of Buffalo and Chief Medical Officer at the Jacobs Institute in Buffalo, New York.
Martin Leon, MD, of Columbia University Medical Center/New York-Presbyterian Hospital, serves as Chairman of the Clinical Steering Committee of the pivotal SENTINEL trial investigating the device. In the company's announcement, Dr. Leon, commented, “The Sentinel device has shown its potential, across multiple trials, to filter and remove brain-borne debris safely, with very few vascular complications. 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."
Claret Medical stated that the landmark SENTINEL trial met its primary safety endpoint of major adverse cardiovascular and cerebral events (MACCE) at 30 days, with a reported MACCE rate in the protected Sentinel group of 7.3%, which is significantly lower than the prespecified historical performance goal of 18.3% and the rate of 9.9% seen in the control arm. The stroke rate for Sentinel-protected patients was 5.6% versus 9.1% for unprotected patients. The observed periprocedural stroke rate—encompassing 72 hours postprocedure—was reduced by 63%, from 8.2% for unprotected patients to 3% for protected patients.
In the trial, device delivery and retrieval were accomplished safely and successfully in 99.6% of cases. The access site complication rate in the Sentinel cohort was 0.4%. 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 sized ≥ 0.5 mm captured in the filters.
Results of the SENTINEL trial were recently published in Journal of the American College of Cardiology by Samir R. Kapadia, MD, et al (2017;69:367–377).
Additionally, the company noted that a meta-analysis of five randomized controlled clinical trials examining cerebral protection in valve repair and replacement procedures across more than 625 patients was recently published by Gennaro Giustino, MD, et al in Journal of the American College of Cardiology (2017;69:463–470).
In the meta-analysis, more than 80% of the patients (510 patients) came from three of the five cited studies, where Claret Medical’s dual-filter CPSs were used. These data demonstrate that the use of cerebral protection is associated with a > 40% lower risk of death or stroke after TAVR. The data corresponded to a rate of one death or stroke potentially being averted for every 22 patients treated with cerebral protection.
Claret Medical noted that the Sentinel CPS has been systematically evaluated in three randomized controlled trials involving more than 600 patients. More than 3,250 patients worldwide have been protected with the device. The Sentinel CPS received European CE Mark approval in 2013.