October 15, 2020
REFLECT II Trial Evaluates Keystone Heart's TriGuard 3 Cerebral Deflection Filter for TAVR
October 15, 2020—The REFLECT II randomized clinical trial evaluating the safety and efficacy of the TriGuard 3 self-stabilizing cerebral embolic deflection filter (Keystone Heart, Ltd., a Venus Medtech company) found that the device met the primary safety endpoint compared to historical controls but did not demonstrate superiority of the device for the primary hierarchical efficacy endpoint. The trial evaluated the safety and effectiveness of the TriGuard 3, which is designed to reduce cerebral embolization and ischemic stroke in patients undergoing transcatheter aortic valve replacement (TAVR).
The findings were reported by Jeffrey W. Moses, MD, at TCT Connect, the 32nd annual Transcatheter Cardiovascular Therapeutics scientific symposium of the Cardiovascular Research Foundation held online October 14–18, 2020.
According to the TCT Connect announcement, REFLECT II was intended to randomize 295 patients 2:1 to TAVR with TriGuard 3 versus a control arm. The primary safety endpoint was a composite of all-cause mortality, stroke, life-threatening or disabling bleeding, stage 2/3 acute kidney injury, coronary artery obstruction requiring intervention, major vascular complication, and valve-related dysfunction requiring intervention (VARC 2 defined) at 30 days. The endpoint was compared with a performance goal (PG) of 34.4%.
The primary efficacy endpoint was a hierarchical composite of all-cause mortality or stroke at 30 days, NIHSS worsening, absence of diffusion-weighted magnetic resonance imaging (DWI) lesions post procedure, and total volume of cerebral lesions (TLV) by DWI. Cumulative scores derived by the Finkelstein-Schoenfeld method were summed for each patient and compared between groups.
The REFLECT II analysis population included 283 patients: 41 roll-in, 121 randomized to TriGuard 3 and 121 controls (58 randomized in phase II and 63 pooled from REFLECT phase I). TriGuard 3 was delivered and positioned in the aortic arch before TAVR in 100% of cases and retrieved intact in all cases.
After enrollment of 179 of the 225 planned randomized patients, the sponsor suspended trial enrollment with the concurrence of the FDA and the Data Monitoring Committee. After limited unblinding and review of the data, Keystone Heart decided to formally close the study and proceed with the FDA 510(k) marketing application.
As summarized by TCT Connect, TriGuard 3 met the primary safety endpoint (22.5% vs 34.4% PG; Pnoninferiority = .0001). However, superiority for the primary efficacy endpoint was not met, with similar win-ratios and win% (TriGuard, 0.84 and 45.7% vs 1.19 and 54.3%; P = .857) between groups. Median TLV was not different with TriGuard 3 protection (215.39 mm3 vs 188.09 mm3; P = .405).
Dr. Moses commented in the TCT Connect press release, “Compared to controls, the primary 30-day safety endpoint was higher with TriGuard 3 primarily because of TAVR-related vascular and bleeding complications. While the study did not demonstrate superiority of TriGuard 3 compared to pooled controls for the primary hierarchical efficacy endpoint, a post hoc DW-MRI analysis suggests that TriGuard 3 may reduce larger ischemic lesions. Improved device stability to achieve reliable, complete cerebral coverage may improve outcomes."