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

NCT03042104 | Active Not Recruiting DMC FDA Device

• 1 other identifier: 2016-07
• Study Type: interventional
• Target: 901
• Locations: 2 countries
• Sites: 77

Brief Summary

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.

Conditions

Heart Diseases; Aortic Stenosis, Severe

Keywords

Aortic valve; Asymptomatic; Transcatheter aortic valve replacement

Outcome Measures

Primary Outcomes (1)

• All-cause death, all stroke, and unplanned cardiovascular hospitalization

  The number of patients that have any of these conditions

  When all patients have reached 2-year follow-up

Secondary Outcomes (5)

• Composite of 1) alive, 2) Kansas City Cardiomyopathy Questionnaire (KCCQ) score ≥75 and 3) KCCQ decrease ≤10 points

  2 years

• Left Ventricular Health

  2 years

• Change in Left Ventricular Ejection Fraction (LVEF)

  2 years

• New onset atrial fibrillation

  When all patients have reached 2-year follow-up

• Death or disabling stroke

  When all patients have reached 2-year follow-up

Study Arms (2)

TAVR

EXPERIMENTAL

Transcatheter aortic valve replacement (TAVR)

Device: Edwards SAPIEN 3 / SAPIEN 3 Ultra THV

CS

NO INTERVENTION

Clinical surveillance (CS)

Interventions

Edwards SAPIEN 3 / SAPIEN 3 Ultra THV DEVICE

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

Also known as: SAPIEN 3, SAPIEN 3 Ultra

TAVR

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Patient is symptomatic
• Patient has any concomitant valvular, aortic, coronary artery disease requiring surgery making AVR a Class I indication.
• Native aortic annulus size unsuitable for sizes 20, 23, 26, or 29 mm THV
• Iliofemoral vessel characteristics that would preclude safe placement of the introducer sheath.
• Left ventricular outflow tract calcification that would increase the risk of annular rupture or significant paravalvular leak post TAVR
• Evidence of an acute myocardial infarction ≤ 30 days before randomization
• Aortic valve is unicuspid, bicuspid with unfavorable features for TAVR, or is non-calcified
• Severe aortic regurgitation (\>3+)
• Severe mitral regurgitation (\>3+) or ≥ moderate mitral stenosis
• Pre-existing mechanical or bioprosthetic valve in any position
• Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 30 days of randomization
• Leukopenia, anemia, thrombocytopenia, history of bleeding diathesis or coagulopathy, or hypercoagulable states
• Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of randomization
• Hypertrophic cardiomyopathy with obstruction
• Cardiac imaging evidence of intracardiac mass, thrombus or vegetation

Sponsors & Collaborators

• Edwards Lifesciences: lead

Study Sites (77)

Banner University Medical Center

Phoenix, Arizona, 85006, United States

Location

Mills Peninsula Health Services

Burlingame, California, 94010, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

Huntington Hospital

Pasadena, California, 91105, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

Kaiser San Francisco Medical Center

San Francisco, California, 94115, United States

Location

Stanford Hospital and Clinics Palo Alto

Stanford, California, 94305, United States

Location

UC Health Northern Colorado (Medical Center of the Rockies)

Loveland, Colorado, 80538, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

Washington Hospital Center DC

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

Location

The Cardiac & Vascular Institute Research Foundation

Gainesville, Florida, 32605, United States

Location

University of Florida

Gainesville, Florida, 32615, United States

Location

Piedmont Heart Institute

Atlanta, Georgia, 30309, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center Chicago

Chicago, Illinois, 60612, United States

Location

NorthShore University HealthSystem Research Institution

Evanston, Illinois, 60201, United States

Location

Alexian Brothers Hospital Network

Lisle, Illinois, 60532, United States

Location

Prairie Education and Research Cooperative

Springfield, Illinois, 62701, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Iowa Heart Center

West Des Moines, Iowa, 50266, United States

Location

Cardiovascular Research Institute of Kansas

Wichita, Kansas, 67226, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Cape Cod Hospital

Hyannis, Massachusetts, 02601, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Minneapolis Heart Institute

Minneapolis, Minnesota, 55407, United States

Location

University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

CentraCare Heart

Saint Cloud, Minnesota, 56303, United States

Location

Saint Luke's Hospital of Kansas City Mid America

Kansas City, Missouri, 64111, United States

Location

St. Patrick Hospital

Missoula, Montana, 59802, United States

Location

Mary Hitchcock Memorial Hospital

Lebanon, New Hampshire, 03756, United States

Location

Atlantic Health System Hospital Corp - Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

Rutgers Robert Wood Johnson Medical School

Piscataway, New Jersey, 08854, United States

Location

Albany Medical College

Albany, New York, 12211, United States

Location

University at Buffalo - Kaleida Health

Buffalo, New York, 14203, United States

Location

NYU Langone Hosptial - Long Island

Mineola, New York, 11501, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Columbia University Medical Center/ New York Presbyterian Hospital

New York, New York, 10032, United States

Location

Cornell University

New York, New York, 10065, United States

Location

Rochester General Hospital

Rochester, New York, 14621, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Carolina's Health System

Charlotte, North Carolina, 28203, United States

Location

NC Heart and Vascular (Rex Hospital)

Raleigh, North Carolina, 27607, United States

Location

The Christ Hospital, Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Mount Carmel Health System

Columbus, Ohio, 43213, United States

Location

The Ohio Health Research Institute

Columbus, Ohio, 43214, United States

Location

Kaiser Portland

Clackamas, Oregon, 97015, United States

Location

Pinnacle Health

Harrisburg, Pennsylvania, 17101, United States

Location

Allegheny - Singer Research Institute

Pittsburgh, Pennsylvania, 15212, United States

Location

Lankenau Medical Center

Wynnewood, Pennsylvania, 19096, United States

Location

York Hospital

York, Pennsylvania, 17403, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

The Heart Hospital Baylor Plano

Dallas, Texas, 75093, United States

Location

Texas Health Physician Group

Dallas, Texas, 75231, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Intermountain Medical Center Salt Lake City

Murray, Utah, 84107, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Inova Heart and Vascular Institute (Fairfax Inova)

Falls Church, Virginia, 22042, United States

Location

Sentara Cardiovascular Research Institute

Norfolk, Virginia, 23507, United States

Location

Carilion Medical Center

Roanoke, Virginia, 24014, United States

Location

Providence Everett

Everett, Washington, 98201, United States

Location

Swedish Medical Center

Seattle, Washington, 98122, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Sacred Heart Medical Center

Spokane, Washington, 99204, United States

Location

CAMC Clinical Trials Center

Charleston, West Virginia, 25304, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Hamilton Health Sciences

Hamilton, Ontario, L8L 2X2, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G2C4, Canada

Location

Related Publications (6)

• Genereux P, Schwartz A, Pibarot P, Lindman BR, Cohen DJ, Oldemeyer JB, Fearon WF, Babaliaros V, Daniels D, Chhatriwalla AK, Suradi HS, Shah PB, Szerlip M, Mack MJ, Dahle T, Goel K, O'Neill WW, Davidson CJ, Makkar RR, Sheth T, Williams M, Russo MJ, Guerrero M, McCabe J, Leipsic J, Zhao Y, Hahn RT, Blanke P, Leon MB. Outcomes of Early vs Delayed Aortic Valve Replacement: Analysis of the EARLY TAVR Valve Implant Population. JACC Cardiovasc Interv. 2025 Nov 24;18(22):2761-2773. doi: 10.1016/j.jcin.2025.09.029.

  PMID: 41297989 DERIVED

• 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.

  PMID: 41128701 DERIVED

• 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.

  PMID: 40163596 DERIVED

• 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.

  PMID: 39466903 DERIVED

• 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.

  PMID: 38056546 DERIVED

• 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.

  PMID: 32774184 DERIVED

MeSH Terms

Conditions

Heart Diseases; Aortic Valve Stenosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Philippe Généreux, MD

  Gagnon Cardiovascular Institute - Morristown Medical Center, Cardiovascular Research Foundation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2017
• First Posted: February 3, 2017
• Study Start: July 12, 2017
• Primary Completion: March 31, 2024
• Study Completion (Estimated): March 1, 2032
• Last Updated: May 13, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (74); CA (3)