AzTrials
AzTrials

Symptomatic Aortic StenosisNCT02536196

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

A study testing Embolic Protection Device and Transcatheter aortic valve implantation (TAVI) in people with Symptomatic Aortic Stenosis, run by Keystone Heart at 30 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The Keystone Heart TriGuard™ HDH is an aortic embolism deflection device intended to reduce the amount of embolic material that may enter the carotid, subclavian, and vertebral arteries during transcatheter heart valve implantation. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Symptomatic Aortic Stenosis
What is being tested?
Embolic Protection Device and Transcatheter aortic valve implantation (TAVI)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
478 participants
Where
30 sitesin 4 countries
Study dates
Jun 2016to Jun 2019
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Subjects must meet ALL of the following criteria:

General Inclusion Criteria

  1. The patient is a male or non-pregnant female ≥18 years of age
  2. The patient meets indications for transcatheter aortic valve implantation (TAVI)
  3. The patient is willing to comply with protocol-specified follow-up evaluations
  4. The patient, or legally authorized representative, has been informed of the nature of the study, agrees to its provisions and has provided written informed consent, approved by the appropriate Institutional Review Board (IRB) or Ethics Committee (EC).

Potential Subjects will be excluded if ANY of the following criteria apply:

General Exclusion Criteria

  1. Patients undergoing transcatheter aortic valve implantation (TAVI) via the trans-axillary, trans-subclavian, or trans-aortic route
  2. Patients undergoing transcatheter aortic valve implantation (TAVI) via the transapical approach due to friable or mobile atherosclerotic plaque in the aortic arch
  3. Patients with a previously implanted prosthetic aortic valve (i.e., planned valve-in-valve transcatheter aortic valve implantation (TAVI))
  4. Pregnant or nursing subjects and those who plan pregnancy in the period up to 1 year following index procedure. Female subjects of child-bearing potential must have a negative pregnancy test done within 14 days prior to index procedure per site standard test
  5. Patients with known diagnosis of acute myocardial infarction (AMI) within 72 hours preceding the index procedure (according to definition) or AMI >72 hours preceding the index procedure, in whom Creatine Kinase (CK) and CK-MB have not returned to within normal limits at the time of procedure, or patients who are currently experiencing clinical symptoms consistent with new-onset AMI, such as nitrate-unresponsive prolonged chest pain
  6. Patients with a history of bleeding diathesis or coagulopathy or patients in whom anti-platelet and/or anticoagulant therapy is contraindicated, patients who will refuse transfusion, or patients with an active peptic ulcer or history of upper gastrointestinal (GI) bleeding within the prior 3 months
  7. Patients with known mental or physical illness or known history of substance abuse that may cause non-compliance with the protocol, confound the data interpretation, or is associated with a life expectancy of less than one year
  8. Patients with severe allergy or known hypersensitivity or contraindication to aspirin, heparin/bivalirudin, clopidogrel, nitinol, stainless steel alloy, and/or contrast sensitivity that cannot be adequately pre-medicated
  9. Patients with a history of a stroke or transient ischemic attack (TIA) within the prior 6 months
  10. Patients with renal failure (estimated Glomerular Filtration Rate [eGFR] <30 mL/min, calculated from serum creatinine by the Cockcroft-Gault formula)
  11. Patients with hepatic failure (Child-Pugh class C)
  12. Patients with hypercoagulable states that cannot be corrected by additional periprocedural heparin
  13. Patients presenting with cardiogenic shock at the time of the index procedure
  14. Patients with severe peripheral arterial, abdominal aortic, or thoracic aortic disease that precludes delivery sheath vascular access
  15. Patients in whom the aortic arch, innominate artery ostium, or proximal innominate artery is heavily calcified, severely atheromatous, or severely tortuous
  16. Patients with an innominate artery ostium diameter <10 mm or >25 mm
  17. Patients with a transverse aortic diameter >43
  18. Patients with anatomic irregularities of the innominate artery that could prevent positioning of the TriGuard upper stabilizer and compromise stability of the device
  19. Patients with any other condition that would prevent adherence to the TriGuard HDH Instructions for Use
  20. Patients with contraindication to cerebral MRI
  21. Patients who have a planned treatment with any other investigational device or procedure during the study period
  22. Patients planned to undergo any other cardiac surgical or interventional procedure (e.g., concurrent coronary revascularization) during the TAVI procedure or within 10 days prior to the TAVI procedure. NOTE: Diagnostic cardiac catheterization is permitted within 10 day prior to the TAVI procedure

Trial locations and contacts

30 sites in 4 countries.

30 sites in 4 countries

United States23 sites
  • Piedmont Hospital

    Atlanta, Georgia, 30309

  • University of Virginia

    Charlottesville, Virginia, 22903

  • Morton Plant Hospital

    Clearwater, Florida, 33756

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Baylor Heart and Vascular HospitalBaylor Heart and Vascular

    Dallas, Texas, 75201

  • Northwestern University

    Evanston, Illinois, 60208

  • Pinnacle Health

    Harrisburg, Pennsylvania, 17101

  • Delray Medical Center

    Hialeah, Florida, 33016

  • Cardiovascular Institute of the South

    Houma, Louisiana, 70360

  • Houston Methodist Hospital

    Houston, Texas, 77030

  • University of Texas

    Houston, Texas, 77030

  • University of Iowa

    Iowa City, Iowa, 52242

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • Yale New Haven Hospital

    New Haven, Connecticut, 06510

  • New York University

    New York, New York, 10016

  • Columbia University Medical Center/NYPH

    New York, New York, 10032

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Baylor Research Center

    Plano, Texas, 75093

  • St. Francis Hospital

    Roslyn, New York, 11576

  • Foundation for Cardiovascular Medicine

    San Diego, California, 92122

  • Swedish Medical Center

    Seattle, Washington, 98122

  • MedStar Washington Hospital Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

Germany4 sites
  • University of Bonn

    Bonn

  • Universitats-Herzzentrum Freiburg

    Freiburg im Breisgau

  • Hamburg Univeristy Cardiovascular Center

    Hamburg

  • Leipzig Heart Institute

    Leipzig

Other trials in Germany

Italy2 sites
  • San Donato Hospital

    Milan

  • San Rafeele Hospital

    Milan

Other trials in Italy

Netherlands1 site
  • UMC Utrecht

    Utrecht

Other trials in Netherlands

About this study

Official title: A Randomized Evaluation of the TriGuard Embolic Deflection Device to Reduce the Impact of Cerebral Embolic Lesions After Transcatheter Aortic Valve Implantation

The Keystone Heart TriGuard™ HDH is an aortic embolism deflection device intended to reduce the amount of embolic material that may enter the carotid, subclavian, and vertebral arteries during transcatheter heart valve implantation.

The objective of the study is to assess the safety and efficacy of the TriGuard™ HDH embolic deflection device in patients undergoing transcatheter aortic valve implantation (TAVI), in comparison with an active control group of patients undergoing unprotected TAVI.

Subjects with indications for TAVI and who meet study eligibility criteria will be randomized 2:1 to one of two treatment arms: 1) Intervention: Embolic protection device (TriGuard™) with transcatheter aortic valve implantation or 2) Control: Unprotected transcatheter aortic valve implantation.

Read the detailed description

This prospective, single-blind, three arm, randomized, (2 device: 1 control), multicenter safety and efficacy trial is designed to enroll up to 603 total subjects in two consecutive phases: Phase I enrolled 258 subjects (including 54 Roll-Ins) and utilized the TriGuard HDH and Phase II will enroll up to 345 subjects (including 40-50 Roll-Ins) and will utilize the TriGUARD 3 (Figure 3b shows the patient flow/disposition).

Phase I In phase I, a total of 204 evaluable subjects and 54 roll-in subjects were enrolled at 26 total investigational sites in the United States, Europe, and Israel, of which 20 sites were in the United States. A minimum of 50% of subjects were planned to be enrolled at US sites, and no single site was permitted to enroll more than 20% of all subjects.

Subjects with indications for TAVI and who met study eligibility criteria were randomized 2:1 (stratified by study site) to one of two treatment arms:

  • Intervention (Phase 1 Cohort) - TAVI with the TriGuard HDH CEPD
  • Control - standard unprotected TAVI At sites where the investigator did not have prior experience with the TriGuard device (minimum of 2 prior cases), up to 3 roll-in subjects were enrolled. Roll-in subjects were not randomized, but underwent TAVI with the TriGuard HDH device. These cases were proctored by a Sponsor representative. Investigational sites with ≥2 prior TriGuard cases were allowed to enroll 1 roll-in subject at the discretion of the site principal investigator.

All subjects were to be followed clinically in-hospital and at 30 and 90 days, and to undergo diffusion-weighted MR imaging 2 to 5 days post-procedure, and neurologic and neuropsychological testing pre-procedure, post-procedure (2-5 days post-procedure), and at 30 and 90 days.

The initial randomized cohort expected to enroll up to 285 subjects. Note: Enrollment in Phase I has been halted after enrolling a total of 258 subjects (54 roll-ins and 204 randomized subjects including 63 controls) based on the recommendation of the Data Monitoring Committee following a review of interim 30-day data on 90 subjects at the prespecified interim analysis time point. A next iteration device designed for increased efficacy, ease of use, and improved safety will be tested in Phase II (below).

Phase II In Phase II, up to 295 randomized subjects and 40-50 roll-in subjects will be enrolled at up to 25 sites in the United States (inclusive of sites enrolling subjects in Phase I). No single site will be permitted to enroll more than 20% of all randomized subjects in Phase II.

Subjects with indications for TAVI and who meet study eligibility criteria will be randomized 2:1 (stratified by study site) to one of two treatment arms:

  • Intervention - TAVI with the TriGUARD 3 CEPD
  • Control - standard unprotected TAVI. Randomization will be stratified by implanted valve type (Medtronic vs. Edwards).

No single valve type will be implanted in more than approximately 70% of randomized patients (phase II).

Roll-in subjects (a minimum of 2 and a maximum of 3 Roll-ins per-site) will not be randomized, but will undergo TAVI with the TriGUARD 3 device. These cases will be proctored by a Sponsor representative.

All subjects will be followed clinically in-hospital and at 30 days, undergo diffusion-weighted MR imaging 2 to 5 days post-procedure, and undergo neurologic (NIHSS) testing pre-procedure, post-procedure (2-5 days post-procedure), and at 30 days. A follow-up phone-call to assess the occurrence of death or stroke will be done at 90 days.

The initial randomized cohort will consist of up to 225 subjects. After at least 50% of the initial randomized cohort (approximately 112 subjects) have reached the 30 day primary efficacy endpoint evaluation time point, a sample size reestimation will be performed in case the conditional power of the trial (assessed by the independent biostatistician) is >40% but <80%, subject to approval by the Sponsor. If this analysis determines that more than 225 randomized subjects will be required to ensure adequate study power, enrollment may continue until the required number of subjects have been enrolled, or until the total subject limit for the study has been reached (whichever occurs first).

Being tested
Embolic Protection Device, Transcatheter aortic valve implantation (TAVI)
Keywords
Aortic stenosis, TAVI, TriGUARD, Keystone Heart, Cerebral Embolic Protection
Medical subject headings
Aortic Valve Stenosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Embolic Protection DeviceDevice

    Embolic protection

  • Transcatheter aortic valve implantation (TAVI)Procedure or surgery

    Transcatheter aortic valve implantation (TAVI)

Study groups in NCT02536196
Study groupRoleWhat they receive
InterventionExperimentalEmbolic Protection with transcatheter aortic valve implantation (TAVI)
Receives: Device: Embolic Protection Device; Procedure: Transcatheter aortic valve implantation (TAVI)
Control ArmActive comparatorTranscatheter aortic valve implantation (TAVI) without embolic protection
Receives: Procedure: Transcatheter aortic valve implantation (TAVI)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Primary Safety Endpoint - Composite Safety Endpoint Based on MACCE

    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.

    Measured: 30 Days

  2. Primary 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.

    Measured: Pre-discharge through 30-days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2015 (estimated)
  2. Study startJun 2016
  3. Primary completionMay 2019
  4. Study completionJun 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
478 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02536196
Sponsor's protocol ID
REFLECT
Status last verified
Feb 2021
First submitted
26 Aug 2015
Last updated
18 Feb 2021
Data monitoring committee
No

Publications

  • Lansky AJ, Grubman D, Dwyer MG 3rd, Zivadinov R, Parise H, Moses JW, Shah T, Pietras C, Tirziu D, Gambone L, Leon MB, Nazif TM, Messe SR. Clinical Significance of Diffusion-Weighted Brain MRI Lesions After TAVR: Results of a Patient-Level Pooled Analysis. J Am Coll Cardiol. 2024 Aug 20;84(8):712-722. doi: 10.1016/j.jacc.2024.05.055.

    PubMed 39142725

Questions about this trial

What is this clinical trial studying?

A study testing Embolic Protection Device and Transcatheter aortic valve implantation (TAVI) in people with Symptomatic Aortic Stenosis, run by Keystone Heart at 30 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in United States, Germany, Italy, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary Safety Endpoint - Composite Safety Endpoint Based on MACCE (time frame: 30 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02536196, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2021.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in