Randomized Evaluation of TriGuard 3 Cerebral Embolic Protection After Transcatheter Aortic Valve Replacement: REFLECT II.

OBJECTIVES

The REFLECT II (Randomized Evaluation of TriGuard 3 Cerebral Embolic Protection After Transcatheter Aortic Valve Implantation) trial was designed to investigate the safety and efficacy of the TriGUARD 3 (TG3) cerebral embolic protection in patients undergoing transcatheter aortic valve replacement.

BACKGROUND

Cerebral embolization occurs frequently following transcatheter aortic valve replacement and procedure-related ischemic stroke occurs in 2% to 6% of patients at 30 days. Whether cerebral protection with TriGuard 3 is safe and effective in reducing procedure-related cerebral injury is not known.

METHODS

This prospective, multicenter, single-blind, 2:1 randomized (TG3 vs. no TG3) study was designed to enroll up to 345 patients. The primary 30-day safety endpoint (Valve Academic Research Consortium-2 defined) was compared with a performance goal (PG). The primary hierarchical composite efficacy endpoint (including death or stroke at 30 days, National Institutes of Health Stroke Scale score worsening in hospital, and cerebral ischemic lesions on diffusion-weighted magnetic resonance imaging at 2 to 5 days) was compared using the Finkelstein-Schoenfeld method.

RESULTS

REFLECT II enrolled 220 of the planned 345 patients (63.8%), including 41 roll-in and 179 randomized patients (121 TG3 and 58 control subjects) at 18 US sites. The sponsor closed the study early after the U.S. Food and Drug Administration recommended enrollment suspension for unblinded safety data review. The trial met its primary safety endpoint compared with the PG (15.9% vs. 34.4% (p < 0.0001). The primary hierarchal efficacy endpoint at 30 days was not met (mean scores [higher is better]: -8.58 TG3 vs. 8.08 control; p = 0.857). A post hoc diffusion-weighted magnetic resonance imaging analysis of per-patient total lesion volume above incremental thresholds showed numeric reductions in total lesion volume >500 mm

CONCLUSIONS

The REFLECT II trial demonstrated that the TG3 was safe compared with a historical PG but did not meet its pre-specified primary superiority efficacy endpoint.

Informations de copyright

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

FUNDING SUPPORT AND Author Disclosures This work was supported by an unrestricted research grant from Keystone Heart. Dr. Nazif has equity in Venus Medtech; and has received consulting fees or honoraria from Keystone Heart, Edwards Lifesciences, Medtronic, and Boston Scientific. Dr. Dhoble has received honoraria from Edwards Lifesciences, Abbott Vascular, and Keystone Heart. Dr. Forrest has received consulting fees from Edwards Lifesciences and Medtronic. Dr. Zivadinov has received personal compensation from Bristol Myers Squibb, EMD Serono, Sanofi, Keystone Heart, Protembis, and Novartis for speaker and consulting fees; and has received financial support for research activities from Sanofi, Novartis, Bristol Myers Squibb, Mapi Pharma, Keystone Heart, Protembis, Boston Scientific, and V-WAVE Medical. Dr. Dwyer has received personal compensation from Novartis, EMD Serono, and Keystone Heart; and has received financial support for research activities from Bristol Myers Squibb, Novartis, Mapi Pharma, Keystone Heart, Protembis, and V-WAVE Medical. Dr. Lansky has equity in Venus Medtech; and has received consulting fees from Keystone Heart, Medtronic, Boston Scientific, and AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.