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AzTrials

Symptomatic Aortic StenosisSMARTNCT04722250

SMall Annuli Randomized To Evolut™ or SAPIEN™ Trial

A study testing Medtronic Evolut PRO, Evolut PRO+ or Evolut FX (where commercially available) TAV Systems and Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems in people with Symptomatic Aortic Stenosis and Aortic Valve Stenosis, run by Medtronic Cardiovascular at 92 sites in 13 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Medtronic Evolut PRO, Evolut PRO+ or Evolut FX (where commercially available) TAV Systems and Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,103 participants
Where
92 sitesin 13 countries
Study dates
2 Apr 2021to Dec 2027
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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

Trial locations and contacts

92 sites in 13 countries.

92 sites in 13 countries

United States61 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Mission Hospital

    Asheville, North Carolina, 28801

  • Emory Structural Heart Clinic and Emory University Midtown

    Atlanta, Georgia, 30308

  • Piedmont Atlanta Hospital

    Atlanta, Georgia, 30309

  • University of Colorado

    Aurora, Colorado, 80045

  • Seton Heart Institute

    Austin, Texas, 78705

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Buffalo General Medical Center

    Buffalo, New York, 14203

  • Saint Vincent Heart Center of Indiana

    Carmel, Indiana, 46290

  • UNC Memorial Hospital

    Chapel Hill, North Carolina, 27599

  • University of Virginia

    Charlottesville, Virginia, 22903

  • TriHealth / Bethesda North Hospital

    Cincinnati, Ohio, 45220

  • Morton Plant Hospital

    Clearwater, Florida, 33756

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Baylor Jack and Jane Hamilton Heart and Vascular Hospital

    Dallas, Texas, 75226

  • Texas Health Presbyterian Hospital/Dallas

    Dallas, Texas, 76231

  • Ascension St. John Hospital

    Detroit, Michigan, 48236

  • NorthShore Health Systems

    Evanston, Illinois, 60201

  • Inova Fairfax Hospital

    Falls Church, Virginia, 22042

  • HealthPark Medical Center

    Fort Myers, Florida, 33908

  • University of Florida

    Gainesville, Florida, 32608

  • Spectrum Health

    Grand Rapids, Michigan, 49503

  • UPMC Pinnacle Harrisburg

    Harrisburg, Pennsylvania, 17110

  • Baylor Saint Luke's Hospital

    Houston, Texas, 77030

  • Houston Methodist Hospital

    Houston, Texas, 77030

  • The University of Texas Health Science Center at Houston

    Houston, Texas, 77030

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

    Houston, Texas, 77030

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Scripps Memorial Hospital

    La Jolla, California, 92037

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Wellstar Kennestone Hospital

    Marietta, Georgia, 30060

  • Mount Sinai Medical Center

    Miami Beach, Florida, 33140

  • J.W. Ruby Memorial Hospital/West Virginia University

    Morgantown, West Virginia, 26506

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • Intermountain Medical Center

    Murray, Utah, 84107

  • TriStar Centennial Medical Center

    Nashville, Tennessee, 37203

  • St. Thomas West Hospital

    Nashville, Tennessee, 37205

  • Yale New Haven Hospital

    New Haven, Connecticut, 06510

  • NYU Langone Medical Center

    New York, New York, 10016

  • The Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

  • Weill Cornell Medical Center

    New York, New York, 10065

  • Sentara Norfolk General Hospital

    Norfolk, Virginia, 23507

  • Advocate Christ Medical Center

    Oak Lawn, Illinois, 60453

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Penn Presbyterian Medical Center

    Philadelphia, Pennsylvania, 19104

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • UPMC Presbyterian

    Pittsburgh, Pennsylvania, 15213

  • The Heart Hospital Baylor Plano

    Plano, Texas, 75093

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • St. Cloud Hospital

    Saint Cloud, Minnesota, 56303

  • Sutter Health

    San Francisco, California, 94109

  • Missouri Baptist Medical Center

    St Louis, Missouri, 63131

  • Saint George Regional Hospital

    St. George, Utah, 84770

  • Los Robles Hospital and Medical Center

    Thousand Oaks, California, 91360

  • Hillcrest Medical Center

    Tulsa, Oklahoma, 74104

  • WHC Washington MedStar

    Washington D.C., District of Columbia, 20010

  • AscensionVia Christi St. Francis Hospital

    Wichita, Kansas, 67226

  • Lankenau Medical Center

    Wynnewood, Pennsylvania, 19096

  • York Hospital

    York, Pennsylvania, 17403

Other trials in United States

Germany8 sites

  • Hers-und Diabeteszentrum NRW - Ruhr -Universitati Bochum

    Bad Oeynhausen

  • Deutsches Herzzentrum Berlin

    Berlin

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

    Dortmund

  • Universitätsklinikum Düsseldorf

    Düsseldorf

  • Universitätsklinikum Schleswig-Holstein - Campus Kiel

    Kiel

  • Helios Health Institute GmbH

    Leipzig

  • Universitätsklinikum Schleswig-Holstein - Campus Lübeck

    Lübeck

  • Deutsches Herzzentrum Munchen

    München

Other trials in Germany

Canada5 sites

  • Montreal Heart Institute

    Montreal, Quebec, H1T 1C8

  • Toronto General Hospital

    Toronto, Ontario, M5G 2C4

  • St. Michaels Hospital/Unity Health Toronto

    Toronto, Ontario

  • Providence Health-St. Paul's Hospital

    Vancouver, British Columbia, V6Z 1Y6

  • Victoria Heart Institute Foundation/Royal Jubilee Hospital

    Victoria, British Columbia

Other trials in Canada

France3 sites

  • Centre Hospitalier Universitaire de Clermont-Ferrand

    Clermont-Ferrand

  • CHU Bordeaux

    Pessac

  • Clinique Pasteur

    Toulouse

Other trials in France

Italy3 sites

  • Policlinico Sant' Orsala - Malpighi

    Bologna

  • Azienda Ospedaliero-Universitaria Pisana - Stabilimento di Cisanello

    Pisa

  • AOU Integrata Verona

    Verona

Other trials in Italy

Netherlands3 sites

  • Catharina Ziekenhuis

    Eindhoven

  • Maastricht Universitair Medisch Centrum (MUMC)

    Maastricht

  • HagaZiekenhuis - Locatie Leyweg

    The Hague

Other trials in Netherlands

Israel2 sites

  • Sheba Medical Center

    Ramat Gan

  • Tel Aviv Sourasky Medical Center

    Tel Aviv

Other trials in Israel

United Kingdom2 sites

  • Royal Infirmary of Edinburgh

    Edinburgh

  • The Leeds Teaching Hospitals NHS Trust - Leeds General Infirmary

    Leeds

Other trials in United Kingdom

Denmark1 site

  • Rigshospitalet

    Copenhagen

Other trials in Denmark

Finland1 site

  • Helsinki University Hospital

    Helsinki

Other trials in Finland

Portugal1 site

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

    Carnaxide

Other trials in Portugal

Spain1 site

  • Hospital Vall d'Hebron

    Barcelona

Other trials in Spain

Switzerland1 site

  • Inselspital - Universitätsspital Bern

    Bern

Other trials in Switzerland

About this study

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.

Read the detailed description

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.

Being tested
Medtronic Evolut PRO, Evolut PRO+ or Evolut FX (where commercially available) TAV Systems, Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems
Medical subject headings
Aortic Valve Stenosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

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

  • Edwards SAPIEN 3 or SAPIEN 3 Ultra THV SystemsDevice

    TAVR treatment with Edwards SAPIEN 3 or SAPIEN 3 Ultra System

Study groups in NCT04722250
Study groupRoleWhat they receive
Medtronic Self-Expanding TAVExperimentalSubjects will be randomized on a 1:1 basis to receive TAVR with either a Medtronic SE TAV or an Edwards BE THV.
Receives: Device: Medtronic Evolut PRO, Evolut PRO+ or Evolut FX (where commercially available) TAV Systems
Edwards Balloon-Expandable THVExperimentalSubjects will be randomized on a 1:1 basis to receive TAVR with either a Medtronic SE TAV or an Edwards BE THV.
Receives: Device: Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mortality, Disabling Stroke or Heart Failure Rehospitalization

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

    Measured: 12 months

  2. 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))

    Measured: 12 months

Secondary outcomes (5)

  1. Percentage of Participants With BVD in Female Subjects

    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)).

    Measured: 12 months

  2. Percentage of Participants With Hemodynamic Structural Valve Dysfunction (HSVD)

    HSVD is defined as hemodynamic mean gradient ≥ 20mmHg on any echocardiogram after implant procedure.

    Measured: 12 months

  3. Hemodynamic Mean Gradient as Continuous Variable

    Mean aortic gradient as measured by echocardiogram at the 12-month visit.

    Measured: 12 months

  4. Effective Orifice Area (EOA) as a Continuous Variable

    Effective Orifice Area (EOA) as measured by echocardiogram at the 12-month visit.

    Measured: 12 months

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

    Moderate or severe PPM will be defined as follows:

    For subjects with BMI < 30 kg/m2

    • Moderate PPM: EOAI = 0.85 - 0.65 cm2/m2
    • Severe PPM: EOAI = ≤ 0.65 cm2/m2

    For subjects with BMI ≥ 30 kg/m2

    • Moderate PPM: EOAI = 0.70 - 0.55 cm2/m2
    • Severe PPM: EOAI = ≤ 0.55 cm2/m2

    Measured: 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2021
  2. Study start2 Apr 2021
  3. Primary completion10 Nov 2023
  4. Study completionDec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,103 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04722250
Sponsor's protocol ID
MDT20023EVR012
Acronym
SMART
Status last verified
May 2026
First submitted
20 Jan 2021
Last updated
2 Jun 2026
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 39382856

  • 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.

    PubMed 38587261

  • 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.

    PubMed 34587510

Questions about this trial

What is this clinical trial studying?

A study testing Medtronic Evolut PRO, Evolut PRO+ or Evolut FX (where commercially available) TAV Systems and Edwards SAPIEN 3 or SAPIEN 3 Ultra THV Systems in people with Symptomatic Aortic Stenosis and Aortic Valve Stenosis, run by Medtronic Cardiovascular at 92 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 2 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 92 sites in United States, Germany, Canada, France, Italy and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mortality, Disabling Stroke or Heart Failure Rehospitalization (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04722250, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2026.

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