Trial Outcomes & Findings for The REFLECT Trial: Cerebral Protection to Reduce Cerebral Embolic Lesions After Transcatheter Aortic Valve Implantation (NCT NCT02536196)

Last Updated: 2021-02-18

Results Overview

Combined safety endpoint at 30 days defined according to VARC-2 ("TAVI early safety") as a composite of: 1. All-cause mortality - number of patients that expired 2. All stroke (disabling and non-disabling) - defined by VARC-2 scale 3. Life-threatening or disabled bleeding - BARC bleeding scale - 5 point scale ranging from no bleeding to fatal 4. Acute kidney injury - Stage 2 or 3 (including renal replacement therapy) 5. Coronary artery obstruction requiring intervention 6. Major vascular complication, and 7. Valve-related dysfunction requiring repeat procedure (BAV, TAVI, or SAVR) - number of patients in whom a valve related dysfunction occurred It was pre-specified to combine all participants that received the device in the andomized Intervention and Roll-in Arms/Groups for this Outcome Measure.

Recruitment status

COMPLETED

Study phase

Target enrollment

478 participants

Primary outcome timeframe

30 Days

Results posted on

2021-02-18

Participant Flow

Participant milestones

Participant milestones
Measure	Intervention Embolic Protection with transcatheter aortic valve implantation (TAVI) Embolic Protection Device: Embolic protection Transcatheter aortic valve implantation (TAVI): Transcatheter aortic valve implantation (TAVI)	Control Arm Transcatheter aortic valve implantation (TAVI) without embolic protection Transcatheter aortic valve implantation (TAVI): Transcatheter aortic valve implantation (TAVI)	Roll-in These are patients that were the initial 2 to 3 patients per site that recieved the device but were used to train physicians but not in the randomized group
Overall Study STARTED	262	121	95
Overall Study COMPLETED	233	107	95
Overall Study NOT COMPLETED	29	14	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The REFLECT Trial: Cerebral Protection to Reduce Cerebral Embolic Lesions After Transcatheter Aortic Valve Implantation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intervention n=262 Participants Embolic Protection with transcatheter aortic valve implantation (TAVI) Embolic Protection Device: Embolic protection Transcatheter aortic valve implantation (TAVI): Transcatheter aortic valve implantation (TAVI)	Control Arm n=121 Participants Transcatheter aortic valve implantation (TAVI) without embolic protection Transcatheter aortic valve implantation (TAVI): Transcatheter aortic valve implantation (TAVI)	Roll-In n=95 Participants Embolic Protection with transcatheter aortic valve implantation (TAVI) Embolic Protection Device: Embolic protection Transcatheter aortic valve implantation (TAVI): Transcatheter aortic valve implantation (TAVI) Only used for training / safety. No efficacy measurements	Total n=478 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Age, Categorical >=65 years	259 Participants n=5 Participants	119 Participants n=7 Participants	93 Participants n=5 Participants	471 Participants n=4 Participants
Sex: Female, Male Female	111 Participants n=5 Participants	44 Participants n=7 Participants	44 Participants n=5 Participants	199 Participants n=4 Participants
Sex: Female, Male Male	151 Participants n=5 Participants	77 Participants n=7 Participants	51 Participants n=5 Participants	279 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	14 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	255 Participants n=5 Participants	116 Participants n=7 Participants	93 Participants n=5 Participants	464 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
Region of Enrollment United States	220 Participants n=5 Participants	108 Participants n=7 Participants	90 Participants n=5 Participants	418 Participants n=4 Participants
Region of Enrollment Europe	42 Participants n=5 Participants	13 Participants n=7 Participants	5 Participants n=5 Participants	60 Participants n=4 Participants
Prior CVA/TIA	38 Participants n=5 Participants	10 Participants n=7 Participants	14 Participants n=5 Participants	62 Participants n=4 Participants

PRIMARY outcome

Timeframe: 30 Days

Population: The population that received the investigational device, Treatment and Rollin patients against safety performance goal. 5 patients withdrew prior to receiving the device resulting in 157 (121Tx+41RI-5). Control patients did not receive the device and were not evaluated in safety endpoint. Composite endpoint is comprised of the number of events against total number of events in accordance with MACCE. The safety endpoint was pre-specified to be calculated separately for the Roll-In population.

Outcome measures

Outcome measures
Measure	Intervention n=157 Participants Embolic Protection with transcatheter aortic valve implantation (TAVI) Embolic Protection Device: Embolic protection Transcatheter aortic valve implantation (TAVI): Transcatheter aortic valve implantation (TAVI)	Control Without CEP
Primary Safety Endpoint - Composite Safety Endpoint Based on MACCE	25 Participants	—

PRIMARY outcome

Timeframe: Pre-discharge through 30-days

Population: eITT population consists of those patients that received the device, i.e. didn't withdraw prior to receiving the investigational device. Of 121 interventional patients in phase 2 of the protocol, 9 patients withdrew before receiving the device. From the total 121 control patients, 2 of the subjects withdrew before receiving the TAVI. There is no theoretical min and max as the number of events could not be known ahead of time, ROLL-IN PATIENTS ARE NOT INCLUDED IN THE EFFICACY ENDPOINT

Hierarchical composite efficacy endpt, determined by pair-wise comparisons among subjects according to hierarchy: * mortality or any stroke \[30 days\] * death/stroke time to event analysis by days determine win * stroke at same day the comparison moves to next tier * NIHSS worsening \[2-5 days post\] * Freedom from lesions detected by DW-MRI 2-5 days post * Total volume lesions detected by DW-MRI 2-5 days post Each subj in intervention compared with each subj from control based on hierarchy according to Finkelstein-Schoenfeld method. If Subj A dies or has stroke \&Subj B survives free of stroke to 30 days, Subj B wins(score+1) \&Subj A loses (score-1). Both die or have stroke, patient with later event wins. Both have death/stroke on same day is equilibrium (score 0). Both are alive \& have stroke on same day, comparison moves to next tier. Both stroke-free to 30 days, comparison moves to the next tier. Scores summed to cumulative score for each subj, \&outcomes between groups are compared.

Outcome measures

Outcome measures
Measure	Intervention n=112 Participants Embolic Protection with transcatheter aortic valve implantation (TAVI) Embolic Protection Device: Embolic protection Transcatheter aortic valve implantation (TAVI): Transcatheter aortic valve implantation (TAVI)	Control n=119 Participants Without CEP
Primary Efficacy Endpoint	587.8 units on a scale Standard Deviation 1028.42	508.2 units on a scale Standard Deviation 1123.96

Adverse Events

Intervention

Serious events: 2 serious events

Other events: 130 other events

Deaths: 4 deaths

Control

Serious events: 2 serious events

Other events: 43 other events

Deaths: 1 deaths

Roll In

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Intervention n=157 participants at risk Embolic Protection with transcatheter aortic valve implantation (TAVI) Embolic Protection Device: Keystone Heart TriGUARD 3	Control n=63 participants at risk The control group received a TAVI but did not receive a cerebral embolic protection device.	Roll In n=41 participants at risk Patients who received the investigational device - TriGUARD 3 but were used for physician training.
Vascular disorders Vascular Bleed	1.3% 2/157 • Number of events 2 • 30 days	3.2% 2/63 • Number of events 2 • 30 days	2.4% 1/41 • Number of events 1 • 30 days

Other adverse events

Other adverse events
Measure	Intervention n=157 participants at risk Embolic Protection with transcatheter aortic valve implantation (TAVI) Embolic Protection Device: Keystone Heart TriGUARD 3	Control n=63 participants at risk The control group received a TAVI but did not receive a cerebral embolic protection device.	Roll In n=41 participants at risk Patients who received the investigational device - TriGUARD 3 but were used for physician training.
Blood and lymphatic system disorders Blood and Lymphatic	15.3% 24/157 • Number of events 29 • 30 days	11.1% 7/63 • Number of events 7 • 30 days	0.00% 0/41 • 30 days
Cardiac disorders Cardiac	52.9% 83/157 • Number of events 122 • 30 days	42.9% 27/63 • Number of events 35 • 30 days	0.00% 0/41 • 30 days
General disorders General Disorders	12.1% 19/157 • Number of events 19 • 30 days	6.3% 4/63 • Number of events 4 • 30 days	0.00% 0/41 • 30 days
Infections and infestations Infections and Infestations	8.3% 13/157 • Number of events 16 • 30 days	7.9% 5/63 • Number of events 5 • 30 days	0.00% 0/41 • 30 days

Additional Information

Pauliina Margolis - CMO

Keystone Heart

Phone: 813.530.8200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place