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

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ClinicalTrials.gov Identifier: NCT02536196
Recruitment Status : Completed
First Posted : August 31, 2015
Results First Posted : February 18, 2021
Last Update Posted : February 18, 2021
Sponsor:
Information provided by (Responsible Party):
Keystone Heart

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Prevention
Condition Symptomatic Aortic Stenosis
Interventions Device: Embolic Protection Device
Procedure: Transcatheter aortic valve implantation (TAVI)
Enrollment 478
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Intervention Control Arm Roll-in
Hide Arm/Group Description

Embolic Protection with transcatheter aortic valve implantation (TAVI)

Embolic Protection Device: Embolic protection

Transcatheter aortic valve implantation (TAVI): Transcatheter aortic valve implantation (TAVI)

Transcatheter aortic valve implantation (TAVI) without embolic protection

Transcatheter aortic valve implantation (TAVI): Transcatheter aortic valve implantation (TAVI)

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
Period Title: Overall Study
Started 262 121 95
Completed 233 107 95
Not Completed 29 14 0
Arm/Group Title Intervention Control Arm Roll-In Total
Hide Arm/Group Description

Embolic Protection with transcatheter aortic valve implantation (TAVI)

Embolic Protection Device: Embolic protection

Transcatheter aortic valve implantation (TAVI): Transcatheter aortic valve implantation (TAVI)

Transcatheter aortic valve implantation (TAVI) without embolic protection

Transcatheter aortic valve implantation (TAVI): Transcatheter aortic valve implantation (TAVI)

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 of all reporting groups
Overall Number of Baseline Participants 262 121 95 478
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 262 participants 121 participants 95 participants 478 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
3
   1.1%
2
   1.7%
2
   2.1%
7
   1.5%
>=65 years
259
  98.9%
119
  98.3%
93
  97.9%
471
  98.5%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 262 participants 121 participants 95 participants 478 participants
Female
111
  42.4%
44
  36.4%
44
  46.3%
199
  41.6%
Male
151
  57.6%
77
  63.6%
51
  53.7%
279
  58.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 262 participants 121 participants 95 participants 478 participants
Hispanic or Latino
7
   2.7%
5
   4.1%
2
   2.1%
14
   2.9%
Not Hispanic or Latino
255
  97.3%
116
  95.9%
93
  97.9%
464
  97.1%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 262 participants 121 participants 95 participants 478 participants
United States
220
  84.0%
108
  89.3%
90
  94.7%
418
  87.4%
Europe
42
  16.0%
13
  10.7%
5
   5.3%
60
  12.6%
Prior CVA/TIA  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 262 participants 121 participants 95 participants 478 participants
38
  14.5%
10
   8.3%
14
  14.7%
62
  13.0%
1.Primary Outcome
Title Primary Safety Endpoint - Composite Safety Endpoint Based on MACCE
Hide Description

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.
Time Frame 30 Days
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Intervention
Hide Arm/Group Description:

Embolic Protection with transcatheter aortic valve implantation (TAVI)

Embolic Protection Device: Embolic protection

Transcatheter aortic valve implantation (TAVI): Transcatheter aortic valve implantation (TAVI)

Overall Number of Participants Analyzed 157
Measure Type: Count of Participants
Unit of Measure: Participants
25
  15.9%
2.Primary Outcome
Title Primary Efficacy Endpoint
Hide Description

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.
Time Frame Pre-discharge through 30-days
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Intervention Control
Hide Arm/Group Description:

Embolic Protection with transcatheter aortic valve implantation (TAVI)

Embolic Protection Device: Embolic protection

Transcatheter aortic valve implantation (TAVI): Transcatheter aortic valve implantation (TAVI)

Without CEP
Overall Number of Participants Analyzed 112 119
Mean (Standard Deviation)
Unit of Measure: units on a scale
587.8  (1028.42) 508.2  (1123.96)
Time Frame 30 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Intervention Control Roll In
Hide Arm/Group Description

Embolic Protection with transcatheter aortic valve implantation (TAVI)

Embolic Protection Device: Keystone Heart TriGUARD 3

The control group received a TAVI but did not receive a cerebral embolic protection device. Patients who received the investigational device - TriGUARD 3 but were used for physician training.
All-Cause Mortality
Intervention Control Roll In
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/157 (2.55%)      1/63 (1.59%)      0/41 (0.00%)    
Hide Serious Adverse Events
Intervention Control Roll In
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/157 (1.27%)      2/63 (3.17%)      1/41 (2.44%)    
Vascular disorders       
Vascular Bleed  1 [1]  2/157 (1.27%)  2 2/63 (3.17%)  2 1/41 (2.44%)  1
1
Term from vocabulary, MedDRA (10.0)
Indicates events were collected by systematic assessment
[1]
vascular complications with closure; not directly related
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Intervention Control Roll In
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   130/157 (82.80%)      43/63 (68.25%)      0/41 (0.00%)    
Blood and lymphatic system disorders       
Blood and Lymphatic  1  24/157 (15.29%)  29 7/63 (11.11%)  7 0/41 (0.00%) 
Cardiac disorders       
Cardiac  1  83/157 (52.87%)  122 27/63 (42.86%)  35 0/41 (0.00%) 
General disorders       
General Disorders  1  19/157 (12.10%)  19 4/63 (6.35%)  4 0/41 (0.00%) 
Infections and infestations       
Infections and Infestations  1  13/157 (8.28%)  16 5/63 (7.94%)  5 0/41 (0.00%) 
1
Term from vocabulary, MedDRA (10.0)
Indicates events were collected by systematic assessment
Study sample size was limited and imbalance in cohorts / randomization
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pauliina Margolis - CMO
Organization: Keystone Heart
Phone: 813.530.8200
EMail: pauliina.margolis@keystoneheart.com
Layout table for additonal information
Responsible Party: Keystone Heart
ClinicalTrials.gov Identifier: NCT02536196    
Other Study ID Numbers: REFLECT
First Submitted: August 26, 2015
First Posted: August 31, 2015
Results First Submitted: October 23, 2020
Results First Posted: February 18, 2021
Last Update Posted: February 18, 2021