PARTNER 3 Trial: Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low Risk Patients With Aortic Stenosis

NCT ID: NCT02675114

Last Updated: 2026-01-14

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

1000 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-31

Study Completion Date

2029-12-31

Brief Summary

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To establish the safety and effectiveness of the Edwards SAPIEN 3 Transcatheter Heart Valve (THV) in patients with severe, calcific aortic stenosis who are at low operative risk for standard aortic valve replacement.

Detailed Description

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Prospective, randomized, controlled, multi-center trial. Patients having an operative mortality \< 4% (low operative risk) for surgical aortic valve replacement will be randomized 1:1 to receive either transcatheter heart valve replacement (TAVR) with the Edwards SAPIEN 3 or aortic valve replacement with a commercially available surgical bioprosthetic valve. Patients will be seen for follow-up visits at discharge, 30 days, 6 months, and annually through 10 years.

A subset of PARTNER 3 randomized patients will be enrolled in the Actigraphy/Quality of Life. Additional patients will be enrolled in either the Bicuspid Registry, Underrepresented Populations Registry (UPR) or the Alternative Access Registry.

Conditions

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Aortic Stenosis

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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Surgical aortic valve replacement (SAVR)

Group Type ACTIVE_COMPARATOR

SAVR

Intervention Type PROCEDURE

SAVR with a commercially available bioprosthetic valve.

Transcatheter aortic valve replacement (TAVR)

Group Type EXPERIMENTAL

SAPIEN 3 THV

Intervention Type DEVICE

TAVR with the Edwards SAPIEN 3 Transcatheter Heart Valve and Edwards Commander Delivery System

Interventions

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SAVR

SAVR with a commercially available bioprosthetic valve.

Intervention Type PROCEDURE

SAPIEN 3 THV

TAVR with the Edwards SAPIEN 3 Transcatheter Heart Valve and Edwards Commander Delivery System

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. Severe, calcific aortic stenosis
2. New York Heart Association Functional Class ≥ 2 OR exercise tolerance test that demonstrates a limited exercise capacity, abnormal BP response, or arrhythmia OR asymptomatic with Left Ventricular Ejection Fraction (LVEF) \<50%
3. Heart team agrees the patient has a risk of operative mortality and has an Society of Thoracic Surgeons (STS) score \< 4
4. The study patient has been informed of the nature of the study, agrees to its provisions and has provided written informed consent.

Exclusion Criteria

1. Native aortic annulus size unsuitable for sizes 20, 23, 26, or 29 mm transcatheter heart valve
2. Iliofemoral vessel characteristics that would preclude safe passage of the introducer sheath
3. Evidence of an acute myocardial infarction ≤ 30 days before randomization
4. Aortic valve is unicuspid, bicuspid, or non-calcified
5. Severe aortic regurgitation (\>3+)
6. Severe mitral regurgitation (\>3+) ≥ moderate stenosis
7. Pre-existing mechanical or bioprosthetic valve in any position
8. Complex coronary artery disease:

1. Unprotected left main coronary artery
2. Syntax score \> 32
3. Heart Team assessment that optimal revascularization cannot be performed
9. Symptomatic carotid or vertebral artery disease or successful treatment of carotid stenosis within 30 days of randomization
10. Leukopenia, anemia, thrombocytopenia, history of bleeding diathesis or coagulopathy, or hypercoagulable states
11. Hemodynamic or respiratory instability requiring inotropic support, mechanical ventilation or mechanical heart assistance within 30 days of randomization
12. Hypertrophic cardiomyopathy with obstruction
13. Ventricular dysfunction with LVEF \< 30%
14. Cardiac imaging evidence of intracardiac mass, thrombus or vegetation
15. Inability to tolerate or condition precluding treatment with antithrombotic/anticoagulation therapy during or after the valve implant procedure
16. Stroke or transient ischemic attack within 90 days of randomization
17. Renal insufficiency and/or renal replacement therapy at the time of screening.
18. Active bacterial endocarditis within 180 days of randomization
19. Severe lung disease or currently on home oxygen
20. Severe pulmonary hypertension
21. History of cirrhosis or any active liver disease
22. Significant frailty as determined by the Heart Team
23. Significant abdominal or thoracic aortic disease that would preclude safe passage of the delivery system or cannulation and aortotomy for surgical aortic valve replacement
24. Hostile chest or conditions or complications from prior surgery that would preclude safe reoperation
25. Patient refuses blood products
26. Body mass index \> 50 kg/m2
27. Estimated life expectancy \< 24 months
28. Absolute contraindications or allergy to iodinated contrast that cannot be adequately treated with pre-medication
29. Immobility that would prevent completion of study procedures
30. Patient is not a candidate for both arms of the study
31. Currently participating in an investigational drug or another device study.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Edwards Lifesciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Martin B Leon, MD, FACC

Role: PRINCIPAL_INVESTIGATOR

Columbia University Medical Center/ New York Presbyterian Hospital, NY

Michael J Mack, MD, FACC

Role: PRINCIPAL_INVESTIGATOR

The Heart Hospital Baylor Plano, TX

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

Banner University Medical Center

Phoenix, Arizona, United States

Site Status

Mills/Peninsula Health Services

Burlingame, California, United States

Site Status

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status

University of California, Los Angeles/Ronald Reagan Medical Center

Los Angeles, California, United States

Site Status

Hoag Hospital

Newport Beach, California, United States

Site Status

Stanford Hospital and Clinics

Palo Alto, California, United States

Site Status

Sutter Health Sacramento

Sacramento, California, United States

Site Status

Kaiser Permanente San Francisco

San Francisco, California, United States

Site Status

UC Health Northern Colorado/Medical Center of the Rockies

Loveland, Colorado, United States

Site Status

Hartford

Hartford, Connecticut, United States

Site Status

JFK Medical Center / Atlantic Clinical Research Collaborative

Atlantis, Florida, United States

Site Status

University of Florida, Gainesville

Gainesville, Florida, United States

Site Status

Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

Florida Hospital

Orlando, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

The Queen's Medical Center

Honolulu, Hawaii, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

NorthShore University HealthSystem Research Institute

Evanston, Illinois, United States

Site Status

Prairie Education and Research Cooperative

Springfield, Illinois, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

Cardiovascular Research Institute of Kansas

Wichita, Kansas, United States

Site Status

UPR - Louisiana State University Health Science Center

New Orleans, Louisiana, United States

Site Status

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

Central Maine Medical Center

Auburn, Maine, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

William Beaumont Hospital

Royal Oak, Michigan, United States

Site Status

University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Saint Luke's Hospital of Kansas City Mid America

Kansas City, Missouri, United States

Site Status

Barnes-Jewish Hospital / Washington University

St Louis, Missouri, United States

Site Status

Nebraska Heart Institute

Lincoln, Nebraska, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Morristown Medical Center / Atlantic Health System Hospital

Morristown, New Jersey, United States

Site Status

Newark Beth Israel

Newark, New Jersey, United States

Site Status

Albany

Albany, New York, United States

Site Status

University of Buffalo

Buffalo, New York, United States

Site Status

Winthrop-University Hospital

Mineola, New York, United States

Site Status

NYU Medical Center

New York, New York, United States

Site Status

Cornell University

New York, New York, United States

Site Status

Columbia University Medical Center/ New York Presbyterian Hospital

New York, New York, United States

Site Status

Carolina's Health System

Charlotte, North Carolina, United States

Site Status

UPR - Novant Health Heart and Vascular Institution

Charlotte, North Carolina, United States

Site Status

Rex Hospital / NC Heart and Vascular Research

Raleigh, North Carolina, United States

Site Status

The Christ Hospital, Cincinnati

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status

Mount Carmel Health System

Columbus, Ohio, United States

Site Status

Oklahoma Cardiovascular Research Group

Oklahoma City, Oklahoma, United States

Site Status

UPR-Oklahoma Heart Institute

Tulsa, Oklahoma, United States

Site Status

Providence Heart & Vascular Institute

Portland, Oregon, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

Lankenau Medical Center

Wynnewood, Pennsylvania, United States

Site Status

York Hospital

York, Pennsylvania, United States

Site Status

Baptist Memorial Hospital

Memphis, Tennessee, United States

Site Status

Saint Thomas Health Services

Nashville, Tennessee, United States

Site Status

Austin Heart

Austin, Texas, United States

Site Status

Medical City Dallas Hospital

Dallas, Texas, United States

Site Status

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status

The Heart Hosptial Baylor Plano

Plano, Texas, United States

Site Status

Intermountain Medical Center

Salt Lake City, Utah, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Fairfax INOVA

Falls Church, Virginia, United States

Site Status

Sentara Cardiovascular Research Institute

Norfolk, Virginia, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Flinders Medical Centre

Bedford Park, South Australia, Australia

Site Status

Saint Paul's Hospital

Vancouver, , Canada

Site Status

Kokura Memorial Hospital

Kitakyushu, Fukuoka, Japan

Site Status

Sendai Kousei Hospital

Sendai, Miyagi, Japan

Site Status

Osaka University

Suita, Osaka, Japan

Site Status

Keio University

Shinjuku, Tokyo, Japan

Site Status

Teikyo University

tabashi City, Tokyo, Japan

Site Status

Auckland City Hospital

Grafton, Auckland, New Zealand

Site Status

Countries

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United States Australia Canada Japan New Zealand

References

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Leon MB, Mack MJ, Pibarot P, Hahn RT, Thourani VH, Kodali SH, Genereux P, Kapadia SR, Cohen DJ, Pocock SJ, Zhang Y, Szerlip M, Ternacle J, Malaisrie SC, Herrmann HC, Szeto WY, Russo MJ, Babaliaros V, Nazif T, Webb JG, Makkar RR; PARTNER 3 Investigators. Transcatheter or Surgical Aortic-Valve Replacement in Low-Risk Patients at 7 Years. N Engl J Med. 2025 Oct 27. doi: 10.1056/NEJMoa2509766. Online ahead of print.

Reference Type DERIVED
PMID: 41144631 (View on PubMed)

Hahn RT, Ternacle J, Silva I, Giuliani C, Zanuttini A, Theron A, Cristell N, Bernier M, Skaf S, Beaudoin J, Kodali SK, Russo M, Kapadia SR, Malaisrie CS, Cohen DJ, Leipsic J, Blanke P, Williams MR, McCabe JM, Brown DL, Babaliaros V, Goldman S, Szeto WY, Genereux P, Pershad A, Park B, Gunnarsson M, Webb JG, Smith CR, Makkar R, Thourani VH, Mack MJ, Leon MB, Pibarot P; PARTNER 3 Investigators. 5-Year Echocardiographic Results of Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients. JACC Cardiovasc Imaging. 2025 Jun;18(6):625-640. doi: 10.1016/j.jcmg.2025.01.015. Epub 2025 Apr 16.

Reference Type DERIVED
PMID: 40243974 (View on PubMed)

Mack MJ, Leon MB, Thourani VH, Pibarot P, Hahn RT, Genereux P, Kodali SK, Kapadia SR, Cohen DJ, Pocock SJ, Lu M, White R, Szerlip M, Ternacle J, Malaisrie SC, Herrmann HC, Szeto WY, Russo MJ, Babaliaros V, Smith CR, Blanke P, Webb JG, Makkar R; PARTNER 3 Investigators. Transcatheter Aortic-Valve Replacement in Low-Risk Patients at Five Years. N Engl J Med. 2023 Nov 23;389(21):1949-1960. doi: 10.1056/NEJMoa2307447. Epub 2023 Oct 24.

Reference Type DERIVED
PMID: 37874020 (View on PubMed)

Genereux P, Cohen DJ, Pibarot P, Redfors B, Bax JJ, Zhao Y, Prince H, Makkar RR, Kapadia S, Thourani VH, Mack MJ, Nazif TM, Lindman BR, Babaliaros V, Russo M, McCabe JM, Gillam LD, Alu MC, Hahn RT, Webb JG, Leon MB, Arnold SV. Cardiac Damage and Quality of Life After Aortic Valve Replacement in the PARTNER Trials. J Am Coll Cardiol. 2023 Feb 28;81(8):743-752. doi: 10.1016/j.jacc.2022.11.059.

Reference Type DERIVED
PMID: 36813373 (View on PubMed)

Kuck KH, Leidl R, Frankenstein L, Wahlers T, Sarmah A, Candolfi P, Shore J, Green M. Cost-Effectiveness of SAPIEN 3 Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement in German Severe Aortic Stenosis Patients at Low Surgical Mortality Risk. Adv Ther. 2023 Mar;40(3):1031-1046. doi: 10.1007/s12325-022-02392-y. Epub 2023 Jan 9.

Reference Type DERIVED
PMID: 36622552 (View on PubMed)

Genereux P, Pibarot P, Redfors B, Bax JJ, Zhao Y, Makkar RR, Kapadia S, Thourani VH, Mack MJ, Nazif TM, Lindman BR, Babaliaros V, Vincent F, Russo M, McCabe JM, Gillam LD, Alu MC, Hahn RT, Webb JG, Leon MB, Cohen DJ. Evolution and Prognostic Impact of Cardiac Damage After Aortic Valve Replacement. J Am Coll Cardiol. 2022 Aug 23;80(8):783-800. doi: 10.1016/j.jacc.2022.05.006. Epub 2022 May 17.

Reference Type DERIVED
PMID: 35595203 (View on PubMed)

Ternacle J, Al-Azizi K, Szerlip M, Potluri S, Hamandi M, Blanke P, Leipsic J, Dahou A, Salaun E, Vincent F, Rogers E, Alu MC, Lu M, Yu X, Thourani VH, Hahn RT, Leon MB, Pibarot P, Mack MJ. Impact of Predilation During Transcatheter Aortic Valve Replacement: Insights From the PARTNER 3 Trial. Circ Cardiovasc Interv. 2021 Jul;14(7):e010336. doi: 10.1161/CIRCINTERVENTIONS.120.010336. Epub 2021 Jun 18.

Reference Type DERIVED
PMID: 34139864 (View on PubMed)

Herrmann HC, Cohen DJ, Hahn RT, Babaliaros VC, Yu X, Makkar R, McCabe J, Szerlip M, Kapadia S, Russo M, Malaisrie SC, Webb JG, Szeto WY, Kodali S, Thourani VH, Mack MJ, Leon MB. Utilization, Costs, and Outcomes of Conscious Sedation Versus General Anesthesia for Transcatheter Aortic Valve Replacement. Circ Cardiovasc Interv. 2021 Jul;14(7):e010310. doi: 10.1161/CIRCINTERVENTIONS.120.010310. Epub 2021 Jun 16.

Reference Type DERIVED
PMID: 34130476 (View on PubMed)

Leon MB, Mack MJ, Hahn RT, Thourani VH, Makkar R, Kodali SK, Alu MC, Madhavan MV, Chau KH, Russo M, Kapadia SR, Malaisrie SC, Cohen DJ, Blanke P, Leipsic JA, Williams MR, McCabe JM, Brown DL, Babaliaros V, Goldman S, Herrmann HC, Szeto WY, Genereux P, Pershad A, Lu M, Webb JG, Smith CR, Pibarot P; PARTNER 3 Investigators. Outcomes 2 Years After Transcatheter Aortic Valve Replacement in Patients at Low Surgical Risk. J Am Coll Cardiol. 2021 Mar 9;77(9):1149-1161. doi: 10.1016/j.jacc.2020.12.052.

Reference Type DERIVED
PMID: 33663731 (View on PubMed)

Pibarot P, Salaun E, Dahou A, Avenatti E, Guzzetti E, Annabi MS, Toubal O, Bernier M, Beaudoin J, Ong G, Ternacle J, Krapf L, Thourani VH, Makkar R, Kodali SK, Russo M, Kapadia SR, Malaisrie SC, Cohen DJ, Leipsic J, Blanke P, Williams MR, McCabe JM, Brown DL, Babaliaros V, Goldman S, Szeto WY, Genereux P, Pershad A, Alu MC, Xu K, Rogers E, Webb JG, Smith CR, Mack MJ, Leon MB, Hahn RT; PARTNER 3 Investigators. Echocardiographic Results of Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients: The PARTNER 3 Trial. Circulation. 2020 May 12;141(19):1527-1537. doi: 10.1161/CIRCULATIONAHA.119.044574. Epub 2020 Apr 10.

Reference Type DERIVED
PMID: 32272848 (View on PubMed)

Mack MJ, Leon MB, Thourani VH, Makkar R, Kodali SK, Russo M, Kapadia SR, Malaisrie SC, Cohen DJ, Pibarot P, Leipsic J, Hahn RT, Blanke P, Williams MR, McCabe JM, Brown DL, Babaliaros V, Goldman S, Szeto WY, Genereux P, Pershad A, Pocock SJ, Alu MC, Webb JG, Smith CR; PARTNER 3 Investigators. Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients. N Engl J Med. 2019 May 2;380(18):1695-1705. doi: 10.1056/NEJMoa1814052. Epub 2019 Mar 16.

Reference Type DERIVED
PMID: 30883058 (View on PubMed)

Leipsic J, Bax JJ, Webb JG, Martin R, Blanke P. Trials Testing the Value of Imaging Use in Valve Disease and in Transcatheter Valvular Interventions. JACC Cardiovasc Imaging. 2017 Mar;10(3):286-295. doi: 10.1016/j.jcmg.2016.09.031.

Reference Type DERIVED
PMID: 28279376 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2015-08

Identifier Type: -

Identifier Source: org_study_id

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