A Randomized Evaluation of the TriGUARD3 Cerebral Embolic Protection Device to Reduce the Impact of Cerebral Embolic Lesions After Transcatheter Aortic Valve Implantation - REFLECT II

Contribution To Literature:

The REFLECT II trial failed to show that cerebral embolic protection with the TriGUARD 3 device during TAVR was beneficial.

Description:

The goal of the trial was to compare cerebral embolic protection with the TriGUARD 3 device compared with usual care among patients undergoing transcatheter aortic valve replacement (TAVR).

Study Design

Subjects who met enrollment criteria were randomized 2:1 to the TriGUARD 3 device versus usual care. There were 121 subjects in the TriGUARD 3 device group versus 58 subjects in the usual care group. There were 41 subjects included from a roll-in phase.

  • Total number of enrollees: 220
  • Duration of follow-up: 30 days
  • Mean patient age: 80 years
  • Percentage female: 45%
  • Percentage with diabetes mellitus: 39%

Inclusion criteria:

  • Severe aortic stenosis with planned TAVR procedure with a commercially available device

Exclusion criteria:

  • Prior AVR
  • Stroke/transient ischemic attack (TIA) <6 months
  • Contraindication to antiplatelet or anticoagulation therapy
  • Estimated glomerular filtration rate (eGFR) <30 ml/min
  • Severe peripheral vascular disease
  • Severe aortic calcification or atheroma
  • Contraindication to magnetic resonance imaging (MRI)

Other salient features/characteristics:

  • Prior stroke/TIA: 17%
  • Bicuspid aortic valve: 25%

Technical success was 71%. During TAVR, 59.3% had complete cerebral coverage, 82.7% had complete or partial coverage, and 17.2% had no coverage.

Principal Findings:

The sponsor closed the trial after the Food and Drug Administration had suspended enrollment for unblinded safety data review. At this point, 220 of 345 subjects had been enrolled.

The primary safety endpoint at 30 days, defined as 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: 15.9% of the cerebral embolic protection device group. The historical performance goal was 34.4% (p for noninferiority = 0.0001). The actual frequency of the composite safety event in the control group was 7.0% (p = 0.11).

The primary efficacy score, defined as all-cause mortality or any stroke at 30 days, National Institutes of Health Stroke Scale (NIHSS) worsening from baseline to 2-5 days, freedom from any cerebral ischemic lesions on diffusion-weighted (DW)-MRI at 2-5 days, and total volume of cerebral ischemic lesions on DW-MRI at 2-5 days: -8.58 in the cerebral embolic protection device group vs. 8.08 in the usual care group (p = 0.86).

Secondary endpoints:

  • All strokes at 30 days: 8.3% of the cerebral embolic protection device group vs. 5.3% of the usual care group (p = not significant)
  • All-cause mortality or any stroke at 30 days: 9.8% of the cerebral embolic protection device group vs. 6.7% of the usual care group (p = 0.48)
  • Life-threatening or disabling bleeding: 5.7% of the cerebral embolic protection device group vs. 0 of the usual care group (p = 0.12)
  • Major vascular complications: 7.0% of the cerebral embolic protection device group vs. 0 of the usual care group (p = 0.04)

Interpretation:

Among patients undergoing TAVR, cerebral embolic protection with the TriGUARD 3 device was not beneficial. This trial was inconclusive due to early termination of the study; however, based on the available data, cerebral embolic protection was associated with a numerically higher incidence of the composite safety endpoint compared with control. Cerebral embolic protection also failed to improve a composite efficacy endpoint. Although an area of intense research, routine cerebral embolic protection during TAVR has not been able to demonstrate a reduction in neurologic events.

References:

Nazif TM, Moses J, Sharma R, et al., on behalf of the REFLECT II Trial Investigators. Randomized Evaluation of TriGuard 3 Cerebral Embolic Protection After Transcatheter Aortic Valve Replacement: REFLECT II. JACC Cardiovasc Interv 2021;14:515-27.

Editorial Comment: Van Mieghem NM, Daemen J. Reflections on the Fate of Cerebral Embolic Protection Devices With TAVR: The REFLECT II Trial. JACC Cardiovasc Interv 2021;14:528-30.

Presented by Dr. Jeffrey W. Moses at the Transcatheter Cardiovascular Therapeutics Virtual Meeting (TCT Connect), October 15, 2020.

Keywords: Acute Kidney Injury, Aortic Valve Stenosis, Cardiac Surgical Procedures, Cerebral Hemorrhage, Diffusion Magnetic Resonance Imaging, Embolic Protection Devices, Embolism, Geriatrics, Heart Valve Diseases, Hemorrhage, Intracranial Embolism, Ischemic Attack, Transient, Stroke, Transcatheter Aortic Valve Replacement, TCT20, Transcatheter Cardiovascular Therapeutics, Vascular Diseases


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