SMall Annuli Randomized To Evolut™ or SAPIEN™ Trial

NCT04722250 | Active Not Recruiting Results DMC FDA Device

• 1 other identifier: MDT20023EVR012
• Study Type: interventional
• Target: 1,103
• Locations: 13 countries
• Sites: 92

Brief Summary

The purpose of this trial is to generate clinical evidence on valve safety and performance of self-expanding (SE) versus balloon-expandable (BE) transcatheter aortic valve replacement (TAVR) in subjects with a small aortic annulus and symptomatic severe native aortic stenosis. Additionally, a stress echocardiography sub-study will be conducted as part of the SMART Trial at select sites. The purpose of the sub-study is to evaluate performance of SE versus BE TAVR in subjects with a small aortic annulus and symptomatic severe native aortic stenosis after undergoing exercise stress echocardiographic testing.

Conditions

Symptomatic Aortic Stenosis; Aortic Valve Stenosis; Aortic Valve Replacement

Outcome Measures

Primary Outcomes (2)

• Mortality, Disabling Stroke or Heart Failure Rehospitalization

  Percentage of participants with all-cause mortality, disabling stroke, or heart failure rehospitalization.

  12 months

• Bioprosthetic Valve Dysfunction (BVD)

  Percentage of participants with BVD as determined by echocardiography (hemodynamic structural valve dysfunction (aortic valve no longer works properly as measured by hemodynamic mean gradient ≥ 20mmHg), non-structural valve dysfunction (severe prosthesis-patient mismatch (valve is too small) and/or ≥ moderate total aortic regurgitation (backward flow of blood)), thrombosis (formation of a blood clot), endocarditis (inflammation of the endocardium - the inner lining of the heart chambers and valves), or aortic valve re-intervention (a follow-up procedure to fix or replace the aortic prosthetic valve))

  12 months

Secondary Outcomes (5)

• Percentage of Participants With BVD in Female Subjects

  12 months

• Percentage of Participants With Hemodynamic Structural Valve Dysfunction (HSVD)

  12 months

• Hemodynamic Mean Gradient as Continuous Variable

  12 months

• Effective Orifice Area (EOA) as a Continuous Variable

  12 months

• Rate of Moderate or Severe Prothesis-patient Mismatch (PPM)

  30 days

Other Outcomes (15)

• Device Success

  30 days

• Incidence of an Early Safety Composite

  30 days

• Hospital Readmission Rate for Any Cause

  30 days

Study Arms (2)

Medtronic Self-Expanding TAV

EXPERIMENTAL

Subjects will be randomized on a 1:1 basis to receive TAVR with either a Medtronic SE TAV or an Edwards BE THV.

Device: Medtronic Evolut PRO, Evolut PRO+ or Evolut FX (where commercially available) TAV Systems

Edwards Balloon-Expandable THV

EXPERIMENTAL

Subjects will be randomized on a 1:1 basis to receive TAVR with either a Medtronic SE TAV or an Edwards BE THV.

Device: Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems

Interventions

Medtronic Evolut PRO, Evolut PRO+ or Evolut FX (where commercially available) TAV Systems DEVICE

TAVR treatment with Medtronic Evolut PRO, PRO+ System or Evolut FX System (where commercially available)

Medtronic Self-Expanding TAV

Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems DEVICE

TAVR treatment with Edwards SAPIEN 3 or SAPIEN 3 Ultra System

Edwards Balloon-Expandable THV

Eligibility Criteria

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

You may qualify if:

• Heart Team agrees that the subject is deemed symptomatic and is a candidate for transcatheter aortic valve replacement (TAVR)
• Subject has a predicted risk of operative mortality \< 15% as determined by the local Heart Team
• Subject has severe aortic stenosis as determined by transthoracic echocardiography (TTE) at rest
• Subject has a small aortic annulus as determined by Multi-detector computed tomography (MDCT)
• Subject's anatomy is appropriate for both Medtronic Evolut PRO/PRO+/FX TAV and Edwards SAPIEN 3/3 Ultra TAV
• Subject's anatomy is suitable for TAVR via transfemoral vessel access
• Subject and the treating physician agree that the subject will return for all required post-procedure follow-up visits

You may not qualify if:

• Estimated life expectancy of fewer than 2 years
• Multivessel coronary artery disease with a Syntax score \>32 and/or unprotected left main coronary artery(Syntax score calculation is not required for patients with history of previous revascularization if repeat revascularization is not planned).
• Participating in another trial that may influence the outcome of this trial
• Need for an emergent procedure for any reason
• Contraindicated for treatment with the Evolut PRO/PRO+/FX and Edwards SAPIEN 3/3 Ultra TAV in accordance with the Instructions for Use
• Other medical, social, or psychological conditions that in the opinion of the Investigator precludes the subject from appropriate consent or adherence to the protocol required follow-up exams
• Pregnant, nursing, or planning to be pregnant
• Subject is less than the legal age of consent, legally incompetent, unable to provide his/her own informed consent, or otherwise vulnerable
• Subject has an active COVID-19 infection or relevant history of COVID-19
• Previous aortic valve replacement

Sponsors & Collaborators

• Medtronic Cardiovascular: lead

Study Sites (92)

Scripps Memorial Hospital

La Jolla, California, 92037, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Sutter Health

San Francisco, California, 94109, United States

Location

Los Robles Hospital and Medical Center

Thousand Oaks, California, 91360, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

WHC Washington MedStar

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

Location

Morton Plant Hospital

Clearwater, Florida, 33756, United States

Location

HealthPark Medical Center

Fort Myers, Florida, 33908, United States

Location

University of Florida

Gainesville, Florida, 32608, United States

Location

Mount Sinai Medical Center

Miami Beach, Florida, 33140, United States

Location

Emory Structural Heart Clinic and Emory University Midtown

Atlanta, Georgia, 30308, United States

Location

Piedmont Atlanta Hospital

Atlanta, Georgia, 30309, United States

Location

Wellstar Kennestone Hospital

Marietta, Georgia, 30060, United States

Location

NorthShore Health Systems

Evanston, Illinois, 60201, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453, United States

Location

Saint Vincent Heart Center of Indiana

Carmel, Indiana, 46290, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

AscensionVia Christi St. Francis Hospital

Wichita, Kansas, 67226, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Ascension St. John Hospital

Detroit, Michigan, 48236, United States

Location

Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

St. Cloud Hospital

Saint Cloud, Minnesota, 56303, United States

Location

Missouri Baptist Medical Center

St Louis, Missouri, 63131, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Buffalo General Medical Center

Buffalo, New York, 14203, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

The Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Mission Hospital

Asheville, North Carolina, 28801, United States

Location

UNC Memorial Hospital

Chapel Hill, North Carolina, 27599, United States

Location

TriHealth / Bethesda North Hospital

Cincinnati, Ohio, 45220, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Hillcrest Medical Center

Tulsa, Oklahoma, 74104, United States

Location

UPMC Pinnacle Harrisburg

Harrisburg, Pennsylvania, 17110, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

UPMC Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

Lankenau Medical Center

Wynnewood, Pennsylvania, 19096, United States

Location

York Hospital

York, Pennsylvania, 17403, United States

Location

TriStar Centennial Medical Center

Nashville, Tennessee, 37203, United States

Location

St. Thomas West Hospital

Nashville, Tennessee, 37205, United States

Location

Seton Heart Institute

Austin, Texas, 78705, United States

Location

Baylor Jack and Jane Hamilton Heart and Vascular Hospital

Dallas, Texas, 75226, United States

Location

Texas Health Presbyterian Hospital/Dallas

Dallas, Texas, 76231, United States

Location

Baylor Saint Luke's Hospital

Houston, Texas, 77030, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

University of Texas Health Sciences Center at Houston - Center for Advanced Heart Failure

Houston, Texas, 77030, United States

Location

The Heart Hospital Baylor Plano

Plano, Texas, 75093, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

Saint George Regional Hospital

St. George, Utah, 84770, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

Location

J.W. Ruby Memorial Hospital/West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Providence Health-St. Paul's Hospital

Vancouver, British Columbia, V6Z 1Y6, Canada

Location

Victoria Heart Institute Foundation/Royal Jubilee Hospital

Victoria, British Columbia, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

St. Michaels Hospital/Unity Health Toronto

Toronto, Ontario, Canada

Location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

Rigshospitalet

Copenhagen, Denmark

Location

Helsinki University Hospital

Helsinki, Finland

Location

Centre Hospitalier Universitaire de Clermont-Ferrand

Clermont-Ferrand, France

Location

CHU Bordeaux

Pessac, France

Location

Clinique Pasteur

Toulouse, France

Location

Hers-und Diabeteszentrum NRW - Ruhr -Universitati Bochum

Bad Oeynhausen, Germany

Location

Deutsches Herzzentrum Berlin

Berlin, Germany

Location

Kath. St.-Johannes-Gesellschaft Dortmund gGmbH - St. Johannes-Hospital Dortmund

Dortmund, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, Germany

Location

Universitätsklinikum Schleswig-Holstein - Campus Kiel

Kiel, Germany

Location

Helios Health Institute GmbH

Leipzig, Germany

Location

Universitätsklinikum Schleswig-Holstein - Campus Lübeck

Lübeck, Germany

Location

Deutsches Herzzentrum Munchen

München, Germany

Location

Sheba Medical Center

Ramat Gan, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

Policlinico Sant' Orsala - Malpighi

Bologna, Italy

Location

Azienda Ospedaliero-Universitaria Pisana - Stabilimento di Cisanello

Pisa, Italy

Location

AOU Integrata Verona

Verona, Italy

Location

Catharina Ziekenhuis

Eindhoven, Netherlands

Location

Maastricht Universitair Medisch Centrum (MUMC)

Maastricht, Netherlands

Location

HagaZiekenhuis - Locatie Leyweg

The Hague, Netherlands

Location

Centro Hospitalar de Lisboa Ocidental, E.P.E. Hospital de Santa Cruz

Carnaxide, Portugal

Location

Hospital Vall d'Hebron

Barcelona, Spain

Location

Inselspital - Universitätsspital Bern

Bern, Switzerland

Location

Royal Infirmary of Edinburgh

Edinburgh, United Kingdom

Location

The Leeds Teaching Hospitals NHS Trust - Leeds General Infirmary

Leeds, United Kingdom

Location

Related Publications (3)

• Tchetche D, Mehran R, Blackman DJ, Khalil RF, Mollmann H, Abdel-Wahab M, Ben Ali W, Mahoney PD, Ruge H, Bleiziffer S, Lin L, Szerlip M, Grubb KJ, Byku I, Guerrero M, Gillam LD, Petronio AS, Attizzani GF, Batchelor WB, Gada H, Rogers T, Rovin JD, Whisenant B, Benton S, Gardner B, Padang R, Althouse AD, Herrmann HC. Transcatheter Aortic Valve Implantation by Valve Type in Women With Small Annuli: Results From the SMART Randomized Clinical Trial. JAMA Cardiol. 2024 Dec 1;9(12):1106-1114. doi: 10.1001/jamacardio.2024.3241.

  PMID: 39382856 DERIVED

• Herrmann HC, Mehran R, Blackman DJ, Bailey S, Mollmann H, Abdel-Wahab M, Ben Ali W, Mahoney PD, Ruge H, Wood DA, Bleiziffer S, Ramlawi B, Gada H, Petronio AS, Resor CD, Merhi W, Garcia Del Blanco B, Attizzani GF, Batchelor WB, Gillam LD, Guerrero M, Rogers T, Rovin JD, Szerlip M, Whisenant B, Deeb GM, Grubb KJ, Padang R, Fan MT, Althouse AD, Tchetche D; SMART Trial Investigators. Self-Expanding or Balloon-Expandable TAVR in Patients with a Small Aortic Annulus. N Engl J Med. 2024 Jun 6;390(21):1959-1971. doi: 10.1056/NEJMoa2312573. Epub 2024 Apr 7.

  PMID: 38587261 DERIVED

• Herrmann HC, Abdel-Wahab M, Attizzani GF, Batchelor W, Bleiziffer S, Verdoliva S, Chang Y, Gada H, Gillam L, Guerrero M, Mahoney PD, Petronio AS, Rogers T, Rovin J, Szerlip M, Whisenant B, Mehran R, Tchetche D. Rationale and design of the SMall Annuli Randomized To Evolut or SAPIEN Trial (SMART Trial). Am Heart J. 2022 Jan;243:92-102. doi: 10.1016/j.ahj.2021.09.011. Epub 2021 Sep 26.

  PMID: 34587510 DERIVED

MeSH Terms

Conditions

Aortic Valve Stenosis

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Myra Fan Director
• Organization: Medtronic Cardiovascular

rs.smarttrial@medtronic.com

763 514 4000

Study Officials

• Howard Herrmann, MD

  University of Pennsylvania, United States

  PRINCIPAL INVESTIGATOR

• Roxana Mehran, MD

  Mount Sinai School of Medicine, United States

  PRINCIPAL INVESTIGATOR

• Didier Tchétché, MD

  Clinique Pasteur Toulouse, France

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

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 20, 2021
• First Posted: January 25, 2021
• Study Start: April 2, 2021
• Primary Completion: November 10, 2023
• Study Completion (Estimated): December 1, 2027
• Last Updated: February 17, 2026
• Results First Posted: March 20, 2025

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1); FR (3); US (61); IT (3); PT (1); GB (2); NL (3); CH (1); ES (1); DK (1); IL (2); DE (8); CA (5)