SENTINEL Trial Evaluates Claret Medical's Cerebral Embolic Protection Device

November 1, 2016—The multicenter, randomized SENTINEL trial evaluating the role of embolic protection using the Sentinel cerebral protection device (Claret Medical, Inc.) during transcatheter aortic valve replacement (TAVR) found that the device was safe but did not meet the primary efficacy endpoint of reduction in median new lesion volume in protected territories as assessed by magnetic resonance imaging (MRI) at 2 to 7 days. In addition, neurocognitive function was not significantly improved.

Findings from the SENTINEL trial were reported at TCT 2016, the 28th annual Transcatheter Cardiovascular Therapeutics scientific symposium in Washington, DC. The study was simultaneously published online ahead of print by the trial’s Coprincipal Investigator Samir R. Kapadia, MD, et al in the Journal of the American College of Cardiology.

The Sentinel transcatheter cerebral embolic protection (TCEP) device consists of two filters within a single 6-F delivery catheter percutaneously placed from the right radial (preferred) or brachial artery over a 0.014-inch guidewire. The filters are positioned in the brachiocephalic and the left common carotid arteries before TAVR and are withdrawn into the catheter and removed after TAVR. The SENTINEL trial was designed to assess the safety of the device during TAVR and the efficacy in reducing the effects of cerebral embolization.

As summarized in the TCT announcement, the prospective, multicenter, randomized trial included 363 patients with severe symptomatic aortic stenosis and planned TAVR who were at high risk for surgery at 17 centers in the United States and two centers in Germany. Patients were randomized 1:1:1 into a safety arm (TCEP only) and two imaging cohorts, in which patients were randomly assigned to TAVR with TCEP (device arm) or without TCEP (control arm). Blinded diffusion-weighted MRI and neurocognitive function assessments were performed in the device and control arms. Particulate debris from the extracted filters was studied in the device arm, and all patients underwent rigorous neurologic evaluations post-TAVR at 30 and 90 days. 

The primary safety endpoint was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs) at 30 days compared to a historical performance goal.

The study found that MACCE (7.3%) in the device and safety arms was noninferior to the performance goal (18.3%; P_{noninferiority} < .001) but was not statistically different from the control (9.9%; P = .41). Despite the finding of histopathologic debris within filters in 99% of patients, which included thrombus, calcification, valve tissue, artery wall, and foreign material, all strokes at 30 days were not significantly different in the device and safety arms versus the control arm (5.6% vs 9.1%; P = .25). 

The median total new lesion volume in protected territories was not significantly different in the device arm compared with the control arm (102.8 mm³ vs 178 mm³; P = .33). However, there were important confounders identified including transcatheter valve type and baseline MRI lesion volume (marker of baseline cerebral disease burden). After adjusting for these factors, embolic protection resulted in reduction of new lesion volume on MRI. Additionally, the findings showed that there was no significant improvement in neurocognitive function associated with embolic protection. However, there was a correlation discovered between new lesion volume and neurocognitive decline (P = .0022). 

In the TCT announcement, Dr. Kodali commented, “Despite not meeting its primary efficacy endpoint, the study does provide evidence of device safety and confirms the high frequency of embolic debris capture with the Sentinel dual-filter neuroprotection therapy. In addition, there are important lessons from this trial which should impact future research on neuroprotection during TAVR.”