A randomized evaluation of the TriGuard™ HDH cerebral embolic protection device to Reduce the Impact of Cerebral Embolic LEsions after TransCatheter Aortic Valve ImplanTation: the REFLECT I trial
Alexandra J. LanskyRajendra MakkarTamim NazifSteven R. MesséJohn K. ForrestRahul SharmaJoachim SchöferAxel LinkeDavid L. BrownAbhijeet DhoblePhillip A. HorwitzMing ZangFrederico DeMarcoVivek RajagopalMichael G. DwyerRobert ZivadinovPieter R. StellaJoshua D. RovinHelen PariseSusheel KodaliAndreas BaumbachJeffrey W. Moses
Key result
TriGuard cerebral embolic protection during TAVR fails to meet predefined effectiveness endpoints versus unprotected controls.
- P=0.31
- n=258
Why the study?
Does the TriGuard HDH cerebral embolic deflection device improve clinical and imaging outcomes in patients undergoing TAVR?
Key Points
- To investigate the safety and clinical effectiveness of the TriGuard HDH cerebral embolic deflection device in patients undergoing transcatheter aortic valve replacement.
- Prospective, multicentre, single-blind trial randomizing patients 2:1 to either the TriGuard HDH device or unprotected transcatheter aortic valve replacement (N=258 enrolled; 54 roll-in and 204 randomized).
- Evaluated a primary 30-day safety endpoint against a performance goal, alongside a primary hierarchical composite efficacy endpoint spanning 30-day mortality/stroke, neurological/cognitive worsening, and DW-MRI lesion volume analyzed via the Finkelstein-Schoenfeld method.
- The primary safety outcome was met compared with the historical performance goal (21.8% vs. 35%, P < 0.0001).
- The primary hierarchical composite efficacy endpoint was not met, showing a mean score of -5.3 ± 99.8 for the device arm versus 11.8 ± 96.4 for controls (P = 0.31).
- Covert central nervous system injury occurred in 46.1% vs. 60.3% in-hospital (P = 0.0698) and 61.7% vs. 76.2% at 5 days (P = 0.054) for the device versus control groups, respectively.
Study Design
Type
RCT (n=258)
Blinding
Single-blind
Randomization
2:1
Multicenter
Yes
Structured PICO
Does the TriGuard HDH cerebral embolic deflection device improve clinical and imaging outcomes in patients undergoing TAVR?
P
Population
258 patients undergoing transcatheter aortic valve replacement (TAVR) followed for 30 days.
I
Intervention
TriGuard™ HDH (TG) cerebral embolic deflection device during TAVR
C
Comparator
No TG (unprotected TAVR controls)
O
Outcome
Primary combined safety endpoint (VARC-2 defined early safety) at 30 days; Primary efficacy endpoint: hierarchical composite of (i) all-cause mortality or any stroke at 30 days, (ii) National Institutes of Health Stroke Scale (NIHSS) worsening at 2-5 days or Montreal Cognitive Assessment worsening at 30 days, and (iii) total volume of cerebral ischaemic lesions detected by diffusion-weighted magnetic resonance imaging at 2-5 dayscomposite
Main Result
Absolute Event Rate: -5.3% vs 11.8%
p-value: p=0.31
The TriGuard HDH cerebral embolic deflection device was safe during TAVR but failed to demonstrate superior efficacy in reducing a hierarchical composite of mortality, stroke, cognitive worsening, and ischemic lesions compared to unprotected TAVR.
Limitations
- Under-enrollment (258 of planned 375 patients enrolled)
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Protecting the brain has become a priority to improve our patients' outcomes, and this is a new focus in interventional cardiology.”
JZJeffrey ZimmetAssociate Professor of Medicine, University of California, San Francisco
“In a world where positive publication bias is a reality, a negative trial like this one seems rare. Seemingly hidden in the text is the fact the authors paused the study early at the recommendation of the Data Safety and Monitoring Board.”
“Knowing what we now know about the significant risks of stroke and other neurological injury associated with TAVI and other cardiovascular procedures, there is a clear unmet clinical need for cerebral embolic protection devices that provide complete protection of all three cerebral branches for patients undergoing these procedures.”
Implication
No role for routine TriGuard CEP in TAVR; challenges prior neuroprotection signals and leaves open next-generation devices.
Abstract
AIMS: The REFLECT I trial investigated the safety and effectiveness of the TriGuard™ HDH (TG) cerebral embolic deflection device in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS AND RESULTS: This prospective, multicentre, single-blind, 2:1 randomized (TG vs. no TG) study aimed to enrol up to 375 patients, including up to 90 roll-in patients. The primary combined safety endpoint (VARC-2 defined early safety) at 30 days was compared with a performance goal. The primary efficacy endpoint was a hierarchical composite of (i) all-cause mortality or any stroke at 30 days, (ii) National Institutes of Health Stroke Scale (NIHSS) worsening at 2-5 days or Montreal Cognitive Assessment worsening at 30 days, and (iii) total volume of cerebral ischaemic lesions detected by diffusion-weighted magnetic resonance imaging at 2-5 days. Cumulative scores were compared between treatment groups using the Finkelstein-Schoenfeld method. A total of 258 of the planned, 375 patients (68.8%) were enrolled (54 roll-in and 204 randomized). The primary safety outcome was met compared with the performance goal (21.8% vs. 35%, P < 0.0001). The primary hierarchical efficacy endpoint was not met (mean efficacy score, higher is better: -5.3 ± 99.8 TG vs. 11.8 ± 96.4 control, P = 0.31). Covert central nervous system injury was numerically lower with TG both in-hospital (46.1% vs. 60.3%, P = 0.0698) and at 5 days (61.7 vs. 76.2%, P = 0.054) compared with controls. CONCLUSION: REFLECT I demonstrated that TG cerebral protection during TAVR was safe in comparison with historical TAVR data but did not meet the predefined effectiveness endpoint compared with unprotected TAVR controls.
Discussion
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Cite This Study
Lansky et al. (2021) conducted an RCT in Transcatheter aortic valve replacement (TAVR) (n=258). TriGuard™ HDH cerebral embolic deflection device vs. Unprotected TAVR controls was evaluated on Hierarchical composite of all-cause mortality or any stroke at 30 days, NIHSS/MoCA worsening, and total volume of cerebral ischaemic lesions at 2-5 days (p=0.31). The TriGuard HDH cerebral embolic deflection device during TAVR met its primary safety performance goal but did not improve the primary hierarchical efficacy endpoint compared to controls (P=0.31).