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

NCT02536196 | Completed Results

• 1 other identifier: REFLECT
• Study Type: interventional
• Target: 478
• Locations: 4 countries
• Sites: 30

Brief 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. 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.

Conditions

Symptomatic Aortic Stenosis

Keywords

Aortic stenosis; TAVI; TriGUARD; Keystone Heart; Cerebral Embolic Protection

Outcome Measures

Primary Outcomes (2)

• 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.

  30 Days

• 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.

  Pre-discharge through 30-days

Study Arms (2)

Intervention

EXPERIMENTAL

Embolic Protection with transcatheter aortic valve implantation (TAVI)

Device: Embolic Protection Device; Procedure: Transcatheter aortic valve implantation (TAVI)

Control Arm

ACTIVE COMPARATOR

Transcatheter aortic valve implantation (TAVI) without embolic protection

Procedure: Transcatheter aortic valve implantation (TAVI)

Interventions

Embolic Protection Device DEVICE

Embolic protection

Intervention

Transcatheter aortic valve implantation (TAVI) PROCEDURE

Transcatheter aortic valve implantation (TAVI)

Control Arm; Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient is a male or non-pregnant female ≥18 years of age
• The patient meets indications for transcatheter aortic valve implantation (TAVI)
• The patient is willing to comply with protocol-specified follow-up evaluations
• 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:

You may not qualify if:

• Patients undergoing transcatheter aortic valve implantation (TAVI) via the trans-axillary, trans-subclavian, or trans-aortic route
• Patients undergoing transcatheter aortic valve implantation (TAVI) via the transapical approach due to friable or mobile atherosclerotic plaque in the aortic arch
• Patients with a previously implanted prosthetic aortic valve (i.e., planned valve-in-valve transcatheter aortic valve implantation (TAVI))
• 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
• 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
• 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
• 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
• 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
• Patients with a history of a stroke or transient ischemic attack (TIA) within the prior 6 months
• Patients with renal failure (estimated Glomerular Filtration Rate \[eGFR\] \<30 mL/min, calculated from serum creatinine by the Cockcroft-Gault formula)
• Patients with hepatic failure (Child-Pugh class C)
• Patients with hypercoagulable states that cannot be corrected by additional periprocedural heparin
• Patients presenting with cardiogenic shock at the time of the index procedure
• Patients with severe peripheral arterial, abdominal aortic, or thoracic aortic disease that precludes delivery sheath vascular access
• Patients in whom the aortic arch, innominate artery ostium, or proximal innominate artery is heavily calcified, severely atheromatous, or severely tortuous

Sponsors & Collaborators

• Keystone Heart: lead

Study Sites (30)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Foundation for Cardiovascular Medicine

San Diego, California, 92122, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

Morton Plant Hospital

Clearwater, Florida, 33756, United States

Location

Delray Medical Center

Hialeah, Florida, 33016, United States

Location

Piedmont Hospital

Atlanta, Georgia, 30309, United States

Location

Northwestern University

Evanston, Illinois, 60208, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Cardiovascular Institute of the South

Houma, Louisiana, 70360, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

New York University

New York, New York, 10016, United States

Location

Columbia University Medical Center/NYPH

New York, New York, 10032, United States

Location

St. Francis Hospital

Roslyn, New York, 11576, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Pinnacle Health

Harrisburg, Pennsylvania, 17101, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor Heart and Vascular HospitalBaylor Heart and Vascular

Dallas, Texas, 75201, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

University of Texas

Houston, Texas, 77030, United States

Location

Baylor Research Center

Plano, Texas, 75093, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

University of Bonn

Bonn, Germany

Location

Universitats-Herzzentrum Freiburg

Freiburg im Breisgau, Germany

Location

Hamburg Univeristy Cardiovascular Center

Hamburg, Germany

Location

Leipzig Heart Institute

Leipzig, Germany

Location

San Donato Hospital

Milan, Italy

Location

San Rafeele Hospital

Milan, Italy

Location

UMC Utrecht

Utrecht, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 39142725 DERIVED

MeSH Terms

Conditions

Aortic Valve Stenosis

Interventions

Embolic Protection Devices; Transcatheter Aortic Valve Replacement

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Intervention Hierarchy (Ancestors)

Prostheses and Implants; Equipment and Supplies; Heart Valve Prosthesis Implantation; Cardiac Surgical Procedures; Cardiovascular Surgical Procedures; Surgical Procedures, Operative; Prosthesis Implantation; Thoracic Surgical Procedures

Limitations and Caveats

Study sample size was limited and imbalance in cohorts / randomization

Results Point of Contact

• Title: Pauliina Margolis - CMO
• Organization: Keystone Heart

pauliina.margolis@keystoneheart.com

813.530.8200

Study Officials

• Alexandra J Lansky, MD

  alexandra.lansky@yale.edu

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2015
• First Posted: August 31, 2015
• Study Start: June 1, 2016
• Primary Completion: May 1, 2019
• Study Completion: June 1, 2019
• Last Updated: February 18, 2021
• Results First Posted: February 18, 2021

Record last verified: 2021-02

Locations

DE (4); IT (2); NL (1); US (23)