EARLY TAVR: Evaluation of TAVR Compared to Surveillance for Patients With Asymptomatic Severe Aortic Stenosis

NCT ID: NCT03042104

Last Updated: 2024-05-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

901 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-12

Study Completion Date

2032-03-31

Brief Summary

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This study will evaluate the safety and effectiveness of the Edwards SAPIEN 3/SAPIEN 3 Ultra Transcatheter Heart Valve (THV) compared with clinical surveillance (CS) in asymptomatic patients with severe, calcific aortic stenosis.

Detailed Description

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This is a prospective, randomized, controlled, multicenter study. Patients will be randomized to receive either transcatheter aortic valve replacement (TAVR) with the Edwards SAPIEN 3 / SAPIEN 3 Ultra THV or clinical surveillance. Patients will be stratified by whether they are able to perform a treadmill stress test. Patients who have a positive stress test will be followed in a registry to collect data on subsequent treatment and mortality, as applicable.

Conditions

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Heart Diseases Aortic Stenosis, Severe

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TAVR

Transcatheter aortic valve replacement (TAVR)

Group Type EXPERIMENTAL

Edwards SAPIEN 3 / SAPIEN 3 Ultra THV

Intervention Type DEVICE

Patients will receive the SAPIEN 3 / SAPIEN 3 Ultra THV.

CS

Clinical surveillance (CS)

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Edwards SAPIEN 3 / SAPIEN 3 Ultra THV

Patients will receive the SAPIEN 3 / SAPIEN 3 Ultra THV.

Intervention Type DEVICE

Other Intervention Names

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SAPIEN 3, SAPIEN 3 Ultra

Eligibility Criteria

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Inclusion Criteria

1. 65 years of age or older
2. Severe aortic stenosis
3. Patient is asymptomatic
4. LV ejection fraction ≥ 50%
5. Society of Thoracic Surgeons (STS) risk score ≤ 10
6. The study patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent.

Exclusion Criteria

1. Patient is symptomatic
2. Patient has any concomitant valvular, aortic, coronary artery disease requiring surgery making AVR a Class I indication.
3. Native aortic annulus size unsuitable for sizes 20, 23, 26, or 29 mm THV
4. Iliofemoral vessel characteristics that would preclude safe placement of the introducer sheath.
5. Left ventricular outflow tract calcification that would increase the risk of annular rupture or significant paravalvular leak post TAVR
6. Evidence of an acute myocardial infarction ≤ 30 days before randomization
7. Aortic valve is unicuspid, bicuspid with unfavorable features for TAVR, or is non-calcified
8. Severe aortic regurgitation (\>3+)
9. Severe mitral regurgitation (\>3+) or ≥ moderate mitral stenosis
10. Pre-existing mechanical or bioprosthetic valve in any position
11. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 30 days of randomization
12. Leukopenia, anemia, thrombocytopenia, history of bleeding diathesis or coagulopathy, or hypercoagulable states
13. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of randomization
14. Hypertrophic cardiomyopathy with obstruction
15. Cardiac imaging evidence of intracardiac mass, thrombus or vegetation
16. Inability to tolerate or condition precluding treatment with anti-thrombotic therapy
17. Stroke or transient ischemic attack within 90 days of randomization
18. Renal insufficiency and/or renal replacement therapy
19. Active bacterial endocarditis within 180 days of randomization
20. Severe lung disease or currently on home oxygen
21. Severe pulmonary hypertension
22. History of cirrhosis or any active liver disease
23. Significant frailty as determined by the Heart Team
24. Significant abdominal or thoracic aortic disease that would preclude safe passage of the delivery system
25. Patient refuses blood products
26. BMI \>50 kg/m2
27. Estimated life expectancy \<24 months
28. Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with pre-medication
29. Currently participating in an investigational drug or another device study.
30. Active SARS-CoV-2 infection (Coronavirus-19 \[COVID-19\]) or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments
Minimum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Edwards Lifesciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Philippe Généreux, MD

Role: PRINCIPAL_INVESTIGATOR

Gagnon Cardiovascular Institute - Morristown Medical Center, Cardiovascular Research Foundation

Locations

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Banner University Medical Center

Phoenix, Arizona, United States

Site Status

Mills Peninsula Health Services

Burlingame, California, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status

Huntington Hospital

Pasadena, California, United States

Site Status

UC Davis Medical Center

Sacramento, California, United States

Site Status

Kaiser San Francisco Medical Center

San Francisco, California, United States

Site Status

Stanford Hospital and Clinics Palo Alto

Stanford, California, United States

Site Status

UC Health Northern Colorado (Medical Center of the Rockies)

Loveland, Colorado, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Washington Hospital Center DC

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

Site Status

The Cardiac & Vascular Institute Research Foundation

Gainesville, Florida, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Piedmont Heart Institute

Atlanta, Georgia, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rush University Medical Center Chicago

Chicago, Illinois, United States

Site Status

NorthShore University HealthSystem Research Institution

Evanston, Illinois, United States

Site Status

Alexian Brothers Hospital Network

Lisle, Illinois, United States

Site Status

Prairie Education and Research Cooperative

Springfield, Illinois, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

Iowa Heart Center

West Des Moines, Iowa, United States

Site Status

Cardiovascular Research Institute of Kansas

Wichita, Kansas, United States

Site Status

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

Maine Medical Center

Portland, Maine, United States

Site Status

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Cape Cod Hospital

Hyannis, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Minneapolis Heart Institute

Minneapolis, Minnesota, United States

Site Status

University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

CentraCare Heart

Saint Cloud, Minnesota, United States

Site Status

Saint Luke's Hospital of Kansas City Mid America

Kansas City, Missouri, United States

Site Status

St. Patrick Hospital

Missoula, Montana, United States

Site Status

Mary Hitchcock Memorial Hospital

Lebanon, New Hampshire, United States

Site Status

Atlantic Health System Hospital Corp - Morristown Medical Center

Morristown, New Jersey, United States

Site Status

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Site Status

Rutgers Robert Wood Johnson Medical School

Piscataway, New Jersey, United States

Site Status

Albany Medical College

Albany, New York, United States

Site Status

University at Buffalo - Kaleida Health

Buffalo, New York, United States

Site Status

NYU Langone Hosptial - Long Island

Mineola, New York, United States

Site Status

New York University Langone Medical Center

New York, New York, United States

Site Status

Columbia University Medical Center/ New York Presbyterian Hospital

New York, New York, United States

Site Status

Cornell University

New York, New York, United States

Site Status

Rochester General Hospital

Rochester, New York, United States

Site Status

Stony Brook University Medical Center

Stony Brook, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Carolina's Health System

Charlotte, North Carolina, United States

Site Status

NC Heart and Vascular (Rex Hospital)

Raleigh, North Carolina, United States

Site Status

The Christ Hospital, Cincinnati

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Mount Carmel Health System

Columbus, Ohio, United States

Site Status

The Ohio Health Research Institute

Columbus, Ohio, United States

Site Status

Kaiser Portland

Clackamas, Oregon, United States

Site Status

Pinnacle Health

Harrisburg, Pennsylvania, United States

Site Status

Allegheny - Singer Research Institute

Pittsburgh, Pennsylvania, United States

Site Status

Lankenau Medical Center

Wynnewood, Pennsylvania, United States

Site Status

York Hospital

York, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

The Heart Hospital Baylor Plano

Dallas, Texas, United States

Site Status

Texas Health Physician Group

Dallas, Texas, United States

Site Status

University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

Intermountain Medical Center Salt Lake City

Murray, Utah, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Inova Heart and Vascular Institute (Fairfax Inova)

Falls Church, Virginia, United States

Site Status

Sentara Cardiovascular Research Institute

Norfolk, Virginia, United States

Site Status

Carilion Medical Center

Roanoke, Virginia, United States

Site Status

Providence Everett

Everett, Washington, United States

Site Status

Swedish Medical Center

Seattle, Washington, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Sacred Heart Medical Center

Spokane, Washington, United States

Site Status

CAMC Clinical Trials Center

Charleston, West Virginia, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

Site Status

Toronto General Hospital

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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Lindman BR, Pibarot P, Schwartz A, Cohen DJ, Giustino G, Oldemeyer JB, Strote JA, Babaliaros V, Devireddy CM, Fearon WF, Fischbein MP, Daniels D, Spies C, Chhatriwalla AK, Kavinsky CJ, Shah P, Szerlip M, Dahle T, Stegman B, O'Leary JM, O'Neill WW, Makkar RR, Davidson CJ, Sheth T, DeVries JT, Southard J, Depta JP, Pop A, Leipsic J, Blanke P, Li Y, Hahn RT, Leon MB, Genereux P. Left Ventricular Health and TAVR Timing in Asymptomatic Severe Aortic Stenosis: Analysis From the EARLY TAVR Trial. J Am Coll Cardiol. 2025 Sep 7:S0735-1097(25)07642-9. doi: 10.1016/j.jacc.2025.08.071. Online ahead of print.

Reference Type DERIVED
PMID: 41128701 (View on PubMed)

Lindman BR, Pibarot P, Schwartz A, Oldemeyer JB, Su YR, Goel K, Cohen DJ, Fearon WF, Babaliaros V, Daniels D, Chhatriwalla A, Suradi HS, Shah P, Szerlip M, Mack MJ, Dahle T, O'Neill WW, Davidson CJ, Makkar R, Sheth T, Depta J, DeVries JT, Southard J, Pop A, Sorajja P, Hahn RT, Zhao Y, Leon MB, Genereux P; EARLY TAVR Trial Executive Committee and Study Investigators. Cardiac Biomarkers in Patients With Asymptomatic Severe Aortic Stenosis: Analysis From the EARLY TAVR Trial. Circulation. 2025 Jun 3;151(22):1550-1564. doi: 10.1161/CIRCULATIONAHA.125.074425. Epub 2025 Mar 31.

Reference Type DERIVED
PMID: 40163596 (View on PubMed)

Genereux P, Schwartz A, Oldemeyer JB, Pibarot P, Cohen DJ, Blanke P, Lindman BR, Babaliaros V, Fearon WF, Daniels DV, Chhatriwalla AK, Kavinsky C, Gada H, Shah P, Szerlip M, Dahle T, Goel K, O'Neill W, Sheth T, Davidson CJ, Makkar RR, Prince H, Zhao Y, Hahn RT, Leipsic J, Redfors B, Pocock SJ, Mack M, Leon MB; EARLY TAVR Trial Investigators. Transcatheter Aortic-Valve Replacement for Asymptomatic Severe Aortic Stenosis. N Engl J Med. 2025 Jan 16;392(3):217-227. doi: 10.1056/NEJMoa2405880. Epub 2024 Oct 28.

Reference Type DERIVED
PMID: 39466903 (View on PubMed)

Genereux P, Schwartz A, Oldemeyer B, Cohen DJ, Redfors B, Prince H, Zhao Y, Lindman BR, Pibarot P, Leon MB. Design and rationale of the evaluation of transcatheter aortic valve replacement compared to surveillance for patients with asymptomatic severe aortic stenosis: The EARLY TAVR trial. Am Heart J. 2024 Feb;268:94-103. doi: 10.1016/j.ahj.2023.11.019. Epub 2023 Dec 4.

Reference Type DERIVED
PMID: 38056546 (View on PubMed)

Zelis JM, Tonino PAL, Pijls NHJ, De Bruyne B, Kirkeeide RL, Gould KL, Johnson NP. Coronary Microcirculation in Aortic Stenosis: Pathophysiology, Invasive Assessment, and Future Directions. J Interv Cardiol. 2020 Jul 22;2020:4603169. doi: 10.1155/2020/4603169. eCollection 2020.

Reference Type DERIVED
PMID: 32774184 (View on PubMed)

Other Identifiers

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2016-07

Identifier Type: -

Identifier Source: org_study_id

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