SMall Annuli Randomized To Evolut™ or SAPIEN™ Trial

NCT ID: NCT04722250

Last Updated: 2025-08-19

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

1103 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-02

Study Completion Date

2027-12-31

Brief Summary

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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.

Detailed Description

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This is a prospective, multi-center, international, randomized controlled, post-market trial.

The primary objectives of the trial are to demonstrate clinical non-inferiority and hemodynamic superiority of the Evolut PRO/PRO+/FX System when compared to subjects treated with the SAPIEN 3/3 Ultra System at 12 months post-procedure.

Subjects will be randomized on a 1:1 basis to receive TAVR with either a Medtronic SE Transcatheter Aortic Valve (TAV) or an Edwards BE Transcatheter Heart Valve (THV). Data will be collected at pre- and post-procedure, at discharge, at 30 days, and once a year until the 5-year follow-up is completed.

Product Names:

* Medtronic Evolut PRO and Evolut PRO+ TAV Systems, Evolut FX System (Commercially available in the United States and may be used upon commercial availability in Canada.)
* Edwards SAPIEN 3 and SAPIEN 3 Ultra THV Systems

The exercise stress echocardiographic testing at select SMART Trial sites seeks to evaluate the performance of the prosthetic aortic valve during exercise. The stress echocardiogram assessment will be conducted as part of the 12-month visit for participating subjects.

Conditions

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Symptomatic Aortic Stenosis Aortic Valve Stenosis Aortic Valve Replacement

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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Medtronic Self-Expanding TAV

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

Group Type EXPERIMENTAL

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

Intervention Type DEVICE

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

Edwards Balloon-Expandable THV

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

Group Type EXPERIMENTAL

Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems

Intervention Type DEVICE

TAVR treatment with Edwards SAPIEN 3 or SAPIEN 3 Ultra System

Interventions

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

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

Intervention Type DEVICE

Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems

TAVR treatment with Edwards SAPIEN 3 or SAPIEN 3 Ultra System

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medtronic Cardiovascular

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Howard Herrmann, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania, United States

Roxana Mehran, MD

Role: PRINCIPAL_INVESTIGATOR

Mount Sinai School of Medicine, United States

Didier Tchétché, MD

Role: PRINCIPAL_INVESTIGATOR

Clinique Pasteur Toulouse, France

Locations

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Scripps Memorial Hospital

La Jolla, California, United States

Site Status

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status

Sutter Health

San Francisco, California, United States

Site Status

Los Robles Hospital and Medical Center

Thousand Oaks, California, United States

Site Status

University of Colorado

Aurora, Colorado, United States

Site Status

Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

WHC Washington MedStar

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

Site Status

Morton Plant Hospital

Clearwater, Florida, United States

Site Status

HealthPark Medical Center

Fort Myers, Florida, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

Emory Structural Heart Clinic and Emory University Midtown

Atlanta, Georgia, United States

Site Status

Piedmont Atlanta Hospital

Atlanta, Georgia, United States

Site Status

Wellstar Kennestone Hospital

Marietta, Georgia, United States

Site Status

NorthShore Health Systems

Evanston, Illinois, United States

Site Status

Advocate Christ Medical Center

Oak Lawn, Illinois, United States

Site Status

Saint Vincent Heart Center of Indiana

Carmel, Indiana, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

AscensionVia Christi St. Francis Hospital

Wichita, Kansas, United States

Site Status

Tufts Medical Center

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Ascension St. John Hospital

Detroit, Michigan, United States

Site Status

Spectrum Health

Grand Rapids, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

St. Cloud Hospital

Saint Cloud, Minnesota, United States

Site Status

Missouri Baptist Medical Center

St Louis, Missouri, United States

Site Status

Morristown Medical Center

Morristown, New Jersey, United States

Site Status

Buffalo General Medical Center

Buffalo, New York, United States

Site Status

NYU Langone Medical Center

New York, New York, United States

Site Status

The Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status

Weill Cornell Medical Center

New York, New York, United States

Site Status

Mission Hospital

Asheville, North Carolina, United States

Site Status

UNC Memorial Hospital

Chapel Hill, North Carolina, United States

Site Status

TriHealth / Bethesda North Hospital

Cincinnati, Ohio, United States

Site Status

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Hillcrest Medical Center

Tulsa, Oklahoma, United States

Site Status

UPMC Pinnacle Harrisburg

Harrisburg, Pennsylvania, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Presbyterian

Pittsburgh, Pennsylvania, United States

Site Status

Lankenau Medical Center

Wynnewood, Pennsylvania, United States

Site Status

York Hospital

York, Pennsylvania, United States

Site Status

TriStar Centennial Medical Center

Nashville, Tennessee, United States

Site Status

St. Thomas West Hospital

Nashville, Tennessee, United States

Site Status

Seton Heart Institute

Austin, Texas, United States

Site Status

Baylor Jack and Jane Hamilton Heart and Vascular Hospital

Dallas, Texas, United States

Site Status

Texas Health Presbyterian Hospital/Dallas

Dallas, Texas, United States

Site Status

Baylor Saint Luke's Hospital

Houston, Texas, United States

Site Status

Houston Methodist Hospital

Houston, Texas, United States

Site Status

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

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

Houston, Texas, United States

Site Status

The Heart Hospital Baylor Plano

Plano, Texas, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

Saint George Regional Hospital

St. George, Utah, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Inova Fairfax Hospital

Falls Church, Virginia, United States

Site Status

Sentara Norfolk General Hospital

Norfolk, Virginia, United States

Site Status

J.W. Ruby Memorial Hospital/West Virginia University

Morgantown, West Virginia, United States

Site Status

Providence Health-St. Paul's Hospital

Vancouver, British Columbia, Canada

Site Status

Victoria Heart Institute Foundation/Royal Jubilee Hospital

Victoria, British Columbia, Canada

Site Status

Toronto General Hospital

Toronto, Ontario, Canada

Site Status

St. Michaels Hospital/Unity Health Toronto

Toronto, Ontario, Canada

Site Status

Montreal Heart Institute

Montreal, Quebec, Canada

Site Status

Rigshospitalet

Copenhagen, , Denmark

Site Status

Helsinki University Hospital

Helsinki, , Finland

Site Status

Centre Hospitalier Universitaire de Clermont-Ferrand

Clermont-Ferrand, , France

Site Status

CHU Bordeaux

Pessac, , France

Site Status

Clinique Pasteur

Toulouse, , France

Site Status

Hers-und Diabeteszentrum NRW - Ruhr -Universitati Bochum

Bad Oeynhausen, , Germany

Site Status

Deutsches Herzzentrum Berlin

Berlin, , Germany

Site Status

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

Dortmund, , Germany

Site Status

Universitätsklinikum Düsseldorf

Düsseldorf, , Germany

Site Status

Universitätsklinikum Schleswig-Holstein - Campus Kiel

Kiel, , Germany

Site Status

Helios Health Institute GmbH

Leipzig, , Germany

Site Status

Universitätsklinikum Schleswig-Holstein - Campus Lübeck

Lübeck, , Germany

Site Status

Deutsches Herzzentrum Munchen

München, , Germany

Site Status

Sheba Medical Center

Ramat Gan, , Israel

Site Status

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Policlinico Sant' Orsala - Malpighi

Bologna, , Italy

Site Status

Azienda Ospedaliero-Universitaria Pisana - Stabilimento di Cisanello

Pisa, , Italy

Site Status

AOU Integrata Verona

Verona, , Italy

Site Status

Catharina Ziekenhuis

Eindhoven, , Netherlands

Site Status

Maastricht Universitair Medisch Centrum (MUMC)

Maastricht, , Netherlands

Site Status

HagaZiekenhuis - Locatie Leyweg

The Hague, , Netherlands

Site Status

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

Carnaxide, , Portugal

Site Status

Hospital Vall d'Hebron

Barcelona, , Spain

Site Status

Inselspital - Universitätsspital Bern

Bern, , Switzerland

Site Status

Royal Infirmary of Edinburgh

Edinburgh, , United Kingdom

Site Status

The Leeds Teaching Hospitals NHS Trust - Leeds General Infirmary

Leeds, , United Kingdom

Site Status

Countries

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United States Canada Denmark Finland France Germany Israel Italy Netherlands Portugal Spain Switzerland United Kingdom

References

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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.

Reference Type DERIVED
PMID: 39382856 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38587261 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34587510 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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MDT20023EVR012

Identifier Type: -

Identifier Source: org_study_id

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