WASHINGTON & SANTA ROSA, Calif.--(BUSINESS WIRE)--Claret Medical® today announced the results from the SENTINEL pivotal IDE trial of the Sentinel® Cerebral Protection System (CPS), used to protect patients’ brains during transcatheter aortic valve replacement (TAVR). Published in Journal of the American College of Cardiology (JACC) today, the data showed that the Sentinel CPS met its primary safety endpoint and exceeded the study observational success criteria of 30 percent treatment effect. The Sentinel CPS also reduced the clinical stroke rate, eliminated peri-procedural strokes and substantially reduced embolic lesion burden, demonstrating that it can make TAVR a safer procedure.
The results were unveiled simultaneously as a Late Breaking Clinical Trial at Transcatheter Cardiovascular Therapeutics (TCT), the annual scientific symposium of the Cardiovascular Research Foundation. The results were presented by national co-primary investigator Susheel Kodali, MD, of Columbia University Medical Center/New York-Presbyterian Hospital on behalf of his co-primary investigators, Samir Kapadia, MD, of The Cleveland Clinic, and Prof. Axel Linke, of The University of Leipzig, Germany.
The landmark SENTINEL trial was a prospective, single blind, multicenter, randomized trial of 363 TAVR patients studied at 19 centers in the U.S. and Germany. Patients were randomized 1:1:1 into a safety arm studying patients protected by the Sentinel CPS, and two imaging arms, in which patients randomly underwent TAVR protected by the Sentinel device or TAVR without protection. The two imaging arms included a serial assessment of new and chronic brain lesions created during the TAVR procedure using diffusion weighted MRI (DW-MRI) and fluid-attenuated inversion recovery MRI (FLAIR). In addition, the patients in the imaging arms simultaneously underwent a comprehensive, neurocognitive function assessment. All 363 patients underwent a rigorous, standardized assessment by neurologists for stroke and other neurological deficits post-TAVR at 30 days and 90 days. Each of these detailed imaging and clinical assessments were reviewed, adjudicated and reported by independent academic core labs and Clinical Events Committees (CEC). The study included the four TAVR valves commercially available in the U.S. as they were approved by the FDA.
The primary safety endpoint was the occurrence of major adverse cardiac and cerebrovascular events (MACCE) at 30 days. This endpoint was met, with MACCE in the two Sentinel CPS treatment arms at 7.3 percent, significantly lower than the pre-specified performance goal of 18.3 percent (p <0.001). Device delivery and retrieval were accomplished safely and successfully throughout the trial at a rate of 99.6 percent. The access site complication rate was only 0.4 percent. Device deployment took less than 10 minutes in 91 percent of cases. The device captured and removed highly heterogeneous embolic debris in 99 percent of patients in the study, including valve tissue, arterial debris, calcification, thrombus and foreign material, demonstrating the need for cerebral protection in the TAVR procedure to remove brain-bound debris.
“The SENTINEL study showed unequivocal evidence of device safety and performance, and confirmed the high frequency of embolic debris capture by the Sentinel,” said Dr. Kodali. “It also demonstrated that the device is compatible with standard cath lab workflow, with virtually no interference with the primary TAVR procedure and minimal time needed for deployment.”
While TAVR is considered the gold standard in treating high-risk aortic stenosis patients, the SENTINEL trial demonstrated that stroke is still a major complication of TAVR, with a stroke rate of 9.1 percent in patients unprotected by the Sentinel device. Use of the Sentinel CPS substantially cut the stroke rate by 39 percent, to 5.6 percent. Importantly, unprotected patients in the control group experienced seven peri-procedural strokes, while there were none in the treatment arm protected by the Sentinel CPS (p= 0.002).
The primary surrogate efficacy endpoint of statistical reduction in median new lesion volume in protected territories of the brain as assessed by DW-MRI at two to seven days after TAVR was not met. However, the trial observational success criteria of a minimum reduction of 30 percent in median new lesion volume in protected territories was exceeded, showing a treatment effect of 42 percent. New findings generated from the study showed that a patient’s pre-existing cerebral lesion burden, as measured by baseline FLAIR, was the strongest predictor of Sentinel effectiveness. After adjusting for this covariate and the effects of valve type and treatment arm interaction, the Sentinel CPS was shown to statistically significantly reduce new lesion volume in both protected (p= 0.0248) and all territories (p= 0.0500) of the brain.
“This study shows us that TAVR-generated brain lesions matter when assessing patient outcomes after TAVR, and that the Sentinel device reduced both clinical neurologic events and neuroimaging evidence of brain embolization,” said Martin Leon, MD, of Columbia University Medical Center/New York-Presbyterian Hospital and founder of the Cardiovascular Research Foundation. “It is also interesting to note that the strokes that did occur in the trial appeared to be less severe when the Sentinel device was used.”
“The SENTINEL study has, for the first time, revealed a strong link between frequency and size of new brain lesions, and neurocognitive deterioration post-TAVR,” said Ronald M. Lazar, PhD, of the Tananbaum Stroke Center, Neurological Institute, Columbia University Medical Center.
“We are gratified that our commitment to science and clinical trial excellence has enabled us to make TAVR a safer procedure and shed light on an important new risk factor in further validating the role of cerebral protection in TAVR,” said Claret Medical President and Chief Executive Officer Azin Parhizgar. “Following our recent marketing application submission, we look forward to working with the FDA to make the Sentinel CPS available to American physicians and their patients who want protection during TAVR.”
The Sentinel CPS is the only device designed to protect the brain by capturing and removing debris dislodged during TAVR that would otherwise enter the cerebral circulation and increase the potential for stroke.
The Sentinel CPS is the most-studied device in the field of TAVR cerebral protection, having been systematically evaluated in three randomized controlled trials involving more than 750 patients. More than 3,000 patients worldwide have been treated with the device to-date.
About Claret Medical
Claret Medical™ is a privately-held company focused on innovative solutions for cerebral protection during structural heart interventions, vascular interventions, and cardiac surgery procedures. The company is currently focusing product development and clinical research on addressing the problem of stroke during TAVR, a significant unmet clinical need. For more information: www.claretmedical.com.
CAUTION: Investigational Device. Limited by United States law to investigational use. Claret Medical and Sentinel are trademarks of Claret Medical, Inc.