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Heart DiseasesEARLY TAVRNCT03042104

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

A study testing Edwards SAPIEN 3 / SAPIEN 3 Ultra THV in people with Heart Diseases and Aortic Stenosis, Severe, run by Edwards Lifesciences at 77 sites in 2 countries.

Active, not recruiting

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

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 65 years and older
Conditions the study is for
Heart Diseases, Aortic Stenosis, Severe
What is being tested?
Edwards SAPIEN 3 / SAPIEN 3 Ultra THV
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
901 participants
Where
77 sitesin 2 countries
Study dates
12 Jul 2017to Mar 2032
Phase
Interventional
Are there results?
Not yet: the study is under way

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 65 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 65 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.

Who cannot join

  • 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
Show all 30Show fewer
  • 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
  • Inability to tolerate or condition precluding treatment with anti-thrombotic therapy
  • Stroke or transient ischemic attack within 90 days of randomization
  • Renal insufficiency and/or renal replacement therapy
  • Active bacterial endocarditis within 180 days of randomization
  • Severe lung disease or currently on home oxygen
  • Severe pulmonary hypertension
  • History of cirrhosis or any active liver disease
  • Significant frailty as determined by the Heart Team
  • Significant abdominal or thoracic aortic disease that would preclude safe passage of the delivery system
  • Patient refuses blood products
  • BMI >50 kg/m2
  • Estimated life expectancy <24 months
  • Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with pre-medication
  • Currently participating in an investigational drug or another device study.
  • Active SARS-CoV-2 infection (Coronavirus-19 [COVID-19]) or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments

Trial locations and contacts

77 sites in 2 countries.

77 sites in 2 countries

United States74 sites

  • Albany Medical College

    Albany, New York, 12211

  • Piedmont Heart Institute

    Atlanta, Georgia, 30309

  • Emory University

    Atlanta, Georgia, 30322

  • University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • University at Buffalo - Kaleida Health

    Buffalo, New York, 14203

  • Mills Peninsula Health Services

    Burlingame, California, 94010

  • CAMC Clinical Trials Center

    Charleston, West Virginia, 25304

  • Carolina's Health System

    Charlotte, North Carolina, 28203

  • University of Virginia

    Charlottesville, Virginia, 22908

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush University Medical Center Chicago

    Chicago, Illinois, 60612

  • The Christ Hospital, Cincinnati

    Cincinnati, Ohio, 45219

  • Kaiser Portland

    Clackamas, Oregon, 97015

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Mount Carmel Health System

    Columbus, Ohio, 43213

  • The Ohio Health Research Institute

    Columbus, Ohio, 43214

  • The Heart Hospital Baylor Plano

    Dallas, Texas, 75093

  • Texas Health Physician Group

    Dallas, Texas, 75231

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • NorthShore University HealthSystem Research Institution

    Evanston, Illinois, 60201

  • Providence Everett

    Everett, Washington, 98201

  • Inova Heart and Vascular Institute (Fairfax Inova)

    Falls Church, Virginia, 22042

  • The Cardiac & Vascular Institute Research Foundation

    Gainesville, Florida, 32605

  • University of Florida

    Gainesville, Florida, 32615

  • Pinnacle Health

    Harrisburg, Pennsylvania, 17101

  • University of Texas Health Science Center at Houston

    Houston, Texas, 77030

  • Cape Cod Hospital

    Hyannis, Massachusetts, 02601

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • Saint Luke's Hospital of Kansas City Mid America

    Kansas City, Missouri, 64111

  • Mary Hitchcock Memorial Hospital

    Lebanon, New Hampshire, 03756

  • Alexian Brothers Hospital Network

    Lisle, Illinois, 60532

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • UC Health Northern Colorado (Medical Center of the Rockies)

    Loveland, Colorado, 80538

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • NYU Langone Hosptial - Long Island

    Mineola, New York, 11501

  • Minneapolis Heart Institute

    Minneapolis, Minnesota, 55407

  • University of Minnesota Medical Center

    Minneapolis, Minnesota, 55455

  • St. Patrick Hospital

    Missoula, Montana, 59802

  • Atlantic Health System Hospital Corp - Morristown Medical Center

    Morristown, New Jersey, 07960

  • Intermountain Medical Center Salt Lake City

    Murray, Utah, 84107

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Yale University

    New Haven, Connecticut, 06510

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

  • New York University Langone Medical Center

    New York, New York, 10016

  • Columbia University Medical Center/ New York Presbyterian Hospital

    New York, New York, 10032

  • Cornell University

    New York, New York, 10065

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Hoag Memorial Hospital Presbyterian

    Newport Beach, California, 92663

  • Sentara Cardiovascular Research Institute

    Norfolk, Virginia, 23507

  • Huntington Hospital

    Pasadena, California, 91105

  • Banner University Medical Center

    Phoenix, Arizona, 85006

  • Rutgers Robert Wood Johnson Medical School

    Piscataway, New Jersey, 08854

  • Allegheny - Singer Research Institute

    Pittsburgh, Pennsylvania, 15212

  • Maine Medical Center

    Portland, Maine, 04102

  • NC Heart and Vascular (Rex Hospital)

    Raleigh, North Carolina, 27607

  • Carilion Medical Center

    Roanoke, Virginia, 24014

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Rochester General Hospital

    Rochester, New York, 14621

  • UC Davis Medical Center

    Sacramento, California, 95817

  • CentraCare Heart

    Saint Cloud, Minnesota, 56303

  • Kaiser San Francisco Medical Center

    San Francisco, California, 94115

  • Swedish Medical Center

    Seattle, Washington, 98122

  • University of Washington

    Seattle, Washington, 98195

  • Sacred Heart Medical Center

    Spokane, Washington, 99204

  • Prairie Education and Research Cooperative

    Springfield, Illinois, 62701

  • Stanford Hospital and Clinics Palo Alto

    Stanford, California, 94305

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • Washington Hospital Center DC

    Washington D.C., District of Columbia, 20010

  • Iowa Heart Center

    West Des Moines, Iowa, 50266

  • Cardiovascular Research Institute of Kansas

    Wichita, Kansas, 67226

  • Lankenau Medical Center

    Wynnewood, Pennsylvania, 19096

  • York Hospital

    York, Pennsylvania, 17403

Other trials in United States

Canada3 sites

  • Hamilton Health Sciences

    Hamilton, Ontario, L8L 2X2

  • University of Ottawa Heart Institute

    Ottawa, Ontario, K1Y 4W7

  • Toronto General Hospital

    Toronto, Ontario, M5G2C4

Other trials in Canada

About this study

Official title: Evaluation of Transcatheter Aortic Valve Replacement Compared to Surveillance for Patients With Asymptomatic Severe Aortic Stenosis

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.

Read the detailed description

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.

Being tested
Edwards SAPIEN 3 / SAPIEN 3 Ultra THV
Keywords
Aortic valve, Asymptomatic, Transcatheter aortic valve replacement
Medical subject headings
Heart Diseases, Aortic Valve Stenosis

What participants receive

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

  • Edwards SAPIEN 3 / SAPIEN 3 Ultra THVDevice

    Also called SAPIEN 3, SAPIEN 3 Ultra

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

Study groups in NCT03042104
Study groupRoleWhat they receive
TAVRExperimentalTranscatheter aortic valve replacement (TAVR)
Receives: Device: Edwards SAPIEN 3 / SAPIEN 3 Ultra THV
CSNo interventionClinical surveillance (CS)

What is being measured

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

  1. All-cause death, all stroke, and unplanned cardiovascular hospitalization

    The number of patients that have any of these conditions

    Measured: When all patients have reached 2-year follow-up

Secondary outcomes (5)

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

    The number of patients that meet all of these criteria

    Measured: 2 years

  2. Left Ventricular Health

    Echocardiographic measurements that will assess the health of the left ventricle

    Measured: 2 years

  3. Change in Left Ventricular Ejection Fraction (LVEF)

    The average change in LVEF from baseline

    Measured: 2 years

  4. New onset atrial fibrillation

    The number of patients that develop this condition

    Measured: When all patients have reached 2-year follow-up

  5. Death or disabling stroke

    The number of patients that have any of these conditions

    Measured: When all patients have reached 2-year follow-up

Timeline

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

  1. First posted3 Feb 2017 (estimated)
  2. Study start12 Jul 2017
  3. Primary completion31 Mar 2024
  4. Study completionMar 2032 (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
901 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03042104
Sponsor's protocol ID
2016-07
Acronym
EARLY TAVR
Status last verified
May 2024
First submitted
30 Jan 2017
Last updated
13 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Genereux P, Schwartz A, Lindman BR, Chhatriwalla A, Ramee S, Babaliaros V, Schwartz R, Sheth T, Fearon WF, Sorajja P, Beaver T, Oldemeyer JB, Pop A, Garcia S, Southard J, Bailey SH, Li W, Cohen DJ, Pibarot P, Leon MB; EARLY TAVR Trial and Registry Investigators. Treadmill Stress Test in Patients With Asymptomatic Severe Aortic Stenosis: A Prespecified Registry-Based Follow-Up of the EARLY TAVR Randomized Clinical Trial. JAMA Cardiol. 2026 Jul 22:e262527. doi: 10.1001/jamacardio.2026.2527. Online ahead of print.

    PubMed 42485012

  • Goel K, Lindman BR, Schwartz A, Cohen DJ, Giustino G, Oldemeyer JB, Strote J, Babaliaros V, Devireddy CM, Fischbein MP, Fearon WF, Daniels D, Spies C, Chhatriwalla AK, Suradi HS, Shah P, Szerlip M, Dahle T, Apostolou D, Makkar R, Davidson CJ, Sheth T, Sorajja P, DeVries JT, Southard J, Depta JP, Pop A, Rinaldi MJ, Badr S, Williams MR, Russo MJ, Guerrero M, McCabe JM, Pibarot P, Wang Y, Leon MB, Genereux P. Age and Procedural Timing for Asymptomatic Severe Aortic Stenosis: Analysis From the EARLY TAVR Trial. Circ Cardiovasc Interv. 2026 Jun 3:e016370. doi: 10.1161/CIRCINTERVENTIONS.125.016370. Online ahead of print.

    PubMed 42233211

  • 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.

    PubMed 41297989

  • 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. 2026 Feb 3;87(4):339-358. doi: 10.1016/j.jacc.2025.08.071. Epub 2025 Sep 7.

    PubMed 41128701

  • 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.

    PubMed 40163596

  • 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.

    PubMed 39466903

  • 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.

    PubMed 38056546

  • 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.

    PubMed 32774184

Questions about this trial

What is this clinical trial studying?

A study testing Edwards SAPIEN 3 / SAPIEN 3 Ultra THV in people with Heart Diseases and Aortic Stenosis, Severe, run by Edwards Lifesciences at 77 sites in 2 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 6 inclusion and 30 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 13 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 77 sites in United States, Canada. 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?

This study is still under way. Results are not available in the source record yet.

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?

All-cause death, all stroke, and unplanned cardiovascular hospitalization (time frame: When all patients have reached 2-year follow-up). 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 NCT03042104, which also lists 8 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 13 May 2024.

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