Trial Outcomes & Findings for Cerebral Protection in Transcatheter Aortic Valve Replacement (NCT NCT02214277)

Last Updated: 2018-05-11

Results Overview

Total new lesion volume is defined as the sum of all diffusion-positive new cerebral lesions in post-TAVR DW-MRI relative to the pre-TAVR DW-MRI scans. Protected territories are defined as brain territories uniquely perfused by the vessels protected by the Sentinel System, namely the left and right carotid arteries, and the right vertebral artery.

Recruitment status

COMPLETED

Study phase

Target enrollment

363 participants

Primary outcome timeframe

Day 2-7 Post-Procedure

Results posted on

2018-05-11

Participant Flow

Participant milestones

Participant milestones
Measure	Safety Arm Safety Arm patients received TAVR and the Sentinel System. Patients enrolled in this arm of the study received safety follow-up at discharge, at 30 days and 90 days post-procedure; and neurological evaluation at baseline, discharge, 30 days and 90 days (only in the case of a stroke ≤ 30 days) post procedure. Safety Arm patients did not receive MRI. The Safety Arm was combined with the Test Arm for analysis of safety endpoints.	Test Arm Test Arm patients received TAVR and the Sentinel System. Patients enrolled in this arm of the study underwent safety follow-up at discharge, at 30 and at 90 days post-procedure; MRI assessment for efficacy at baseline, 2-7 days and 30 days post-procedure; neurological evaluation at baseline, discharge, 30 days and 90 days (only in the case of a stroke ≤ 30 days) post procedure; neurocognitive evaluation at baseline, 2-7 days (optional), 30 days and 90 days post-procedure; Quality of Life assessment at baseline, 30 days and 90 days; and histopathological evaluation of debris captured in the Sentinel device filters. The Test Arm was compared to the Control Arm for analysis of MRI related endpoints, and was combined with the Safety Arm for analysis of safety endpoints.	Control Arm Control Arm patients received TAVR only. Patients enrolled in this arm of the study underwent safety follow-up at discharge, at 30 and at 90 days post-procedure; MRI assessment for efficacy at baseline, 2-7 days and 30 days post-procedure; neurological evaluation at baseline, discharge, 30 days and 90 days (only in the case of a stroke ≤ 30 days) post procedure; neurocognitive evaluation at baseline, 2-7 days (optional), 30 days and 90 days post-procedure; and Quality of Life assessment at baseline, 30 days and 90 days. The Control Arm was compared to the Test arm for MRI related endpoints.
Overall Study STARTED	123	121	119
Overall Study COMPLETED	104	96	85
Overall Study NOT COMPLETED	19	25	34

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Cerebral Protection in Transcatheter Aortic Valve Replacement

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Safety Arm n=123 Participants Safety Arm patients received TAVR and the Sentinel System. Patients enrolled in this arm of the study received safety follow-up at discharge, at 30 days and 90 days post-procedure; and neurological evaluation at baseline, discharge, 30 days and 90 days (only in the case of a stroke ≤ 30 days) post procedure.	Test Arm n=121 Participants Test Arm patients received TAVR and the Sentinel System. Patients enrolled in this arm of the study underwent safety follow-up at discharge, at 30 and at 90 days post-procedure; MRI assessment for efficacy at baseline, 2-7 days and 30 days post-procedure; neurological evaluation at baseline, discharge, 30 days and 90 days (only in the case of a stroke ≤ 30 days) post procedure; neurocognitive evaluation at baseline, 2-7 days (optional), 30 days and 90 days post-procedure; Quality of Life assessment at baseline, 30 days and 90 days; and histopathological evaluation of debris captured in the Sentinel device filters.	Control Arm n=119 Participants Control Arm patients received TAVR only. Patients enrolled in this arm of the study underwent safety follow-up at discharge, at 30 and at 90 days post-procedure; MRI assessment for efficacy at baseline, 2-7 days and 30 days post-procedure; neurological evaluation at baseline, discharge, 30 days and 90 days (only in the case of a stroke ≤ 30 days) post procedure; neurocognitive evaluation at baseline, 2-7 days (optional), 30 days and 90 days post-procedure; and Quality of Life assessment at baseline, 30 days and 90 days.	Total n=363 Participants Total of all reporting groups
Age, Continuous	81.5 years STANDARD_DEVIATION 8.98 • n=5 Participants	82.0 years STANDARD_DEVIATION 7.95 • n=7 Participants	83.4 years STANDARD_DEVIATION 7.90 • n=5 Participants	82.3 years STANDARD_DEVIATION 8.31 • n=4 Participants
Sex: Female, Male Female	68 Participants n=5 Participants	63 Participants n=7 Participants	58 Participants n=5 Participants	189 Participants n=4 Participants
Sex: Female, Male Male	55 Participants n=5 Participants	58 Participants n=7 Participants	61 Participants n=5 Participants	174 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	123 Participants n=5 Participants	118 Participants n=7 Participants	118 Participants n=5 Participants	359 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	10 Participants n=4 Participants
Race (NIH/OMB) White	109 Participants n=5 Participants	115 Participants n=7 Participants	115 Participants n=5 Participants	339 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Region of Enrollment United States	98 participants n=5 Participants	95 participants n=7 Participants	96 participants n=5 Participants	289 participants n=4 Participants
Region of Enrollment Germany	25 participants n=5 Participants	26 participants n=7 Participants	23 participants n=5 Participants	74 participants n=4 Participants
STS PROM Score	6.2 units on a scale STANDARD_DEVIATION 3.17 • n=5 Participants	6.4 units on a scale STANDARD_DEVIATION 3.28 • n=7 Participants	7.5 units on a scale STANDARD_DEVIATION 4.66 • n=5 Participants	6.7 units on a scale STANDARD_DEVIATION 3.79 • n=4 Participants
History of Atrial Fibrillation	37 Participants n=5 Participants	42 Participants n=7 Participants	36 Participants n=5 Participants	115 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 2-7 Post-Procedure

Population: ITT with Imputation. Test Arm compared to the Control Arm.

Outcome measures

Outcome measures
Measure	Test Arm n=121 Participants Test Arm patients received TAVR and the Sentinel System. Patients enrolled in this arm of the study underwent safety followup at discharge, at 30 and at 90 days postprocedure; MRI assessment for efficacy at baseline, 2-7 days and 30 days postprocedure; neurological evaluation at baseline, discharge, 30 days and 90 days (only in the case of a stroke ≤ 30 days) post procedure; neurocognitive evaluation at baseline, 2-7 days (optional), 30 days and 90 days postprocedure; Quality of Life assessment at baseline, 30 days and 90 days; and histopathological evaluation of debris captured in the Sentinel device filters.	Control Arm n=119 Participants Control Arm patients received TAVR only. Patients enrolled in this arm of the study underwent safety follow-up at discharge, at 30 and at 90 days post-procedure; MRI assessment for efficacy at baseline, 2-7 days and 30 days post-procedure; neurological evaluation at baseline, discharge, 30 days and 90 days (only in the case of a stroke ≤ 30 days) post procedure; neurocognitive evaluation at baseline, 2-7 days (optional), 30 days and 90 days post-procedure; and Quality of Life assessment at baseline, 30 days and 90 days.
Reduction in Median Total New Lesion Volume in Protected Territories Between Test and Control Arms as Assessed by DW-MRI at Day 2-7 Post-procedure.	109.1 mm3 Interval 36.9 to 379.7	174 mm3 Interval 39.6 to 469.3

PRIMARY outcome

Timeframe: 30 Days Post-Procedure

Population: Safety Arm and Test Arm. ITT with imputation.

Primary Safety Endpoint: MACCE (all death, all stroke, and acute kidney injury class 3 within 72 hours or discharge, whatever occurs first) at 30 days compared to a historical performance goal of 18.3%.

Outcome measures

Outcome measures
Measure	Test Arm n=244 Participants Test Arm patients received TAVR and the Sentinel System. Patients enrolled in this arm of the study underwent safety followup at discharge, at 30 and at 90 days postprocedure; MRI assessment for efficacy at baseline, 2-7 days and 30 days postprocedure; neurological evaluation at baseline, discharge, 30 days and 90 days (only in the case of a stroke ≤ 30 days) post procedure; neurocognitive evaluation at baseline, 2-7 days (optional), 30 days and 90 days postprocedure; Quality of Life assessment at baseline, 30 days and 90 days; and histopathological evaluation of debris captured in the Sentinel device filters.	Control Arm Control Arm patients received TAVR only. Patients enrolled in this arm of the study underwent safety follow-up at discharge, at 30 and at 90 days post-procedure; MRI assessment for efficacy at baseline, 2-7 days and 30 days post-procedure; neurological evaluation at baseline, discharge, 30 days and 90 days (only in the case of a stroke ≤ 30 days) post procedure; neurocognitive evaluation at baseline, 2-7 days (optional), 30 days and 90 days post-procedure; and Quality of Life assessment at baseline, 30 days and 90 days.
Patients With Major Adverse Cardiac and Cerebrovascular Events (MACCE) at 30 Days	18 Participants	—

SECONDARY outcome

Timeframe: Post-procedure

Population: Only Test Arm patients had debris samples collected. Only samples with evaluable filters were used in the analysis.

Outcome measures

Outcome measures
Measure	Test Arm n=105 Participants Test Arm patients received TAVR and the Sentinel System. Patients enrolled in this arm of the study underwent safety followup at discharge, at 30 and at 90 days postprocedure; MRI assessment for efficacy at baseline, 2-7 days and 30 days postprocedure; neurological evaluation at baseline, discharge, 30 days and 90 days (only in the case of a stroke ≤ 30 days) post procedure; neurocognitive evaluation at baseline, 2-7 days (optional), 30 days and 90 days postprocedure; Quality of Life assessment at baseline, 30 days and 90 days; and histopathological evaluation of debris captured in the Sentinel device filters.	Control Arm Control Arm patients received TAVR only. Patients enrolled in this arm of the study underwent safety follow-up at discharge, at 30 and at 90 days post-procedure; MRI assessment for efficacy at baseline, 2-7 days and 30 days post-procedure; neurological evaluation at baseline, discharge, 30 days and 90 days (only in the case of a stroke ≤ 30 days) post procedure; neurocognitive evaluation at baseline, 2-7 days (optional), 30 days and 90 days post-procedure; and Quality of Life assessment at baseline, 30 days and 90 days.
Captured Debris Histopathology (Observational) Debris present	104 Participants	—
Captured Debris Histopathology (Observational) No debris present	1 Participants	—

Adverse Events

Safety Cohort (Test + Safety Arms)

Serious events: 17 serious events

Other events: 158 other events

Deaths: 11 deaths

Control Arm

Serious events: 11 serious events

Other events: 79 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Safety Cohort (Test + Safety Arms) n=244 participants at risk The Safety Cohort is the combination of the Safety and Test Arms. Patients enrolled in these arms of the study underwent safety follow-up at discharge, at 30 and at 90 days post-procedure.	Control Arm n=119 participants at risk Control Arm patients received TAVR only. Patients enrolled in this arm of the study underwent safety follow-up at discharge, at 30 and at 90 days post-procedure.
Cardiac disorders Death	1.2% 3/244 • Number of events 3 • 0-30 days	1.7% 2/119 • Number of events 2 • 0-30 days
Nervous system disorders Stroke	5.3% 13/244 • Number of events 13 • 0-30 days	8.4% 10/119 • Number of events 10 • 0-30 days
Renal and urinary disorders Acute Kidney Injury	0.41% 1/244 • Number of events 1 • 0-30 days	0.00% 0/119 • 0-30 days

Other adverse events

Other adverse events
Measure	Safety Cohort (Test + Safety Arms) n=244 participants at risk The Safety Cohort is the combination of the Safety and Test Arms. Patients enrolled in these arms of the study underwent safety follow-up at discharge, at 30 and at 90 days post-procedure.	Control Arm n=119 participants at risk Control Arm patients received TAVR only. Patients enrolled in this arm of the study underwent safety follow-up at discharge, at 30 and at 90 days post-procedure.
General disorders Abnormal Lab Value	6.1% 15/244 • Number of events 18 • 0-30 days	6.7% 8/119 • Number of events 9 • 0-30 days
Injury, poisoning and procedural complications Access Site Hematoma	5.3% 13/244 • Number of events 13 • 0-30 days	5.0% 6/119 • Number of events 6 • 0-30 days
Blood and lymphatic system disorders Anemia	9.4% 23/244 • Number of events 24 • 0-30 days	9.2% 11/119 • Number of events 11 • 0-30 days
Cardiac disorders Arrhythmia	5.3% 13/244 • Number of events 14 • 0-30 days	8.4% 10/119 • Number of events 10 • 0-30 days
Cardiac disorders Cardiac Arrest	1.6% 4/244 • Number of events 4 • 0-30 days	5.0% 6/119 • Number of events 6 • 0-30 days
General disorders Bleed, Operative or Post-Operative	4.9% 12/244 • Number of events 13 • 0-30 days	5.0% 6/119 • Number of events 6 • 0-30 days
Cardiac disorders Conduction System Injury	17.2% 42/244 • Number of events 47 • 0-30 days	25.2% 30/119 • Number of events 36 • 0-30 days
General disorders Fever	6.1% 15/244 • Number of events 15 • 0-30 days	2.5% 3/119 • Number of events 3 • 0-30 days
General disorders Hypertension	4.5% 11/244 • Number of events 11 • 0-30 days	7.6% 9/119 • Number of events 9 • 0-30 days
Nervous system disorders Neurological Event, Imaging Only	12.3% 30/244 • Number of events 31 • 0-30 days	19.3% 23/119 • Number of events 24 • 0-30 days
General disorders Other	21.7% 53/244 • Number of events 74 • 0-30 days	25.2% 30/119 • Number of events 42 • 0-30 days

Additional Information

Director of Clinical Research

Claret Medical

Phone: 707-528-9300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place