The ENCIRCLE Trial

NCT04153292 | Recruiting DMC FDA Device

• 1 other identifier: 2018-19
• Study Type: interventional
• Target: 900
• Locations: 6 countries
• Sites: 68

Brief Summary

This study will establish the safety and effectiveness of the SAPIEN M3 System in subjects with symptomatic, at least 3+ mitral regurgitation (MR) for whom commercially available surgical or transcatheter treatment options are deemed unsuitable. Following completion of enrollment, subjects will be eligible for enrollment in the continued access phase of the trial.

Conditions

Mitral Regurgitation; Mitral Valve Insufficiency

Outcome Measures

Primary Outcomes (1)

• Non-hierarchical composite of death and heart failure rehospitalization

  Number of subjects with death and/or heart failure rehospitalization

  1 year

Secondary Outcomes (4)

• Improvement in NYHA functional class compared to baseline

  1 year

• Improvement in KCCQ Overall Score compared to baseline

  1 year

• Improvement in MR compared to baseline

  1 year

• Decrease in LVEDVi compared to baseline

  1 year

Study Arms (3)

TMVR - Main Cohort

EXPERIMENTAL

Subjects for whom commercially available surgical or transcatheter treatment options are deemed unsuitable will have transcatheter mitral valve replacement (TMVR).

Device: SAPIEN M3 valve and dock

TMVR - Failed TEER Registry

EXPERIMENTAL

Subjects who have had an attempted but failed transcatheter edge-to-edge repair (TEER) procedure will have TMVR.

Device: SAPIEN M3 valve and dock

TMVR - MAC Registry

EXPERIMENTAL

Subjects with mitral annular calcification (MAC) will have TMVR.

Device: SAPIEN M3 valve and dock

Interventions

SAPIEN M3 valve and dock DEVICE

During the procedure a SAPIEN M3 dock and a SAPIEN M3 valve will be implanted via transseptal approach.

TMVR - Failed TEER Registry; TMVR - MAC Registry; TMVR - Main Cohort

Eligibility Criteria

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

You may qualify if:

• years of age or older
• MR ≥ 3+
• NYHA functional class ≥ II
• Per the Heart Team, commercially available surgical or transcatheter treatment options are deemed unsuitable due to clinical, anatomic or technical considerations.
• Subject's heart failure management has been optimized based on subject characteristics and applicable guidelines, and stable for at least 30 days prior to enrollment.
• The subject or subject's legal representative has been informed of the nature of the study, agrees to its provisions and has provided written informed consent.

You may not qualify if:

• Mitral/cardiac anatomy that would preclude appropriate delivery and deployment of the SAPIEN M3 dock or valve
• Inappropriate anatomy for femoral introduction and delivery of the SAPIEN M3 dock and valve
• Presence of any device that will contact or interfere with the SAPIEN M3 System during delivery or after implantation
• Left ventricular ejection fraction \<25%
• Severe right ventricular dysfunction
• Need for aortic, tricuspid or pulmonic valve intervention within the next 12 months
• History of heart transplant
• Cardiac imaging evidence of intracardiac mass, thrombus or vegetation
• Active bacterial endocarditis within 180 days of the procedure
• Hemodynamic instability requiring inotropic or mechanical support within 30 days of the procedure
• Myocardial infarction within 30 days of the procedure
• Clinically significant untreated coronary artery disease requiring revascularization
• Any percutaneous cardiovascular intervention, cardiovascular surgery, or carotid surgery within 30 days of the procedure
• Stroke or transient ischemic attack within 90 days of the procedure
• Irreversible, severe pulmonary hypertension

Sponsors & Collaborators

• Edwards Lifesciences: lead

Study Sites (68)

Heart Center Hospital

Huntsville, Alabama, 35801, United States

ACTIVE NOT RECRUITING

Banner University Medical Center

Phoenix, Arizona, 85006, United States

ACTIVE NOT RECRUITING

Saint Josephs Hospital Medical Center Dignity Health

Phoenix, Arizona, 85013, United States

ACTIVE NOT RECRUITING

TMC Healthcare

Tucson, Arizona, 85712, United States

WITHDRAWN

Scripps Health

La Jolla, California, 92037, United States

ACTIVE NOT RECRUITING

Good Samaritan Hospital

Los Angeles, California, 90017, United States

ACTIVE NOT RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

ACTIVE NOT RECRUITING

Kaiser Sunset LA

Los Angeles, California, 90071, United States

ACTIVE NOT RECRUITING

Saint Joseph Hospital

Orange, California, 92868, United States

WITHDRAWN

California Pacific Medical Center

San Francisco, California, 94109, United States

ACTIVE NOT RECRUITING

UC Health Northern Colorado (Medical Center of the Rockies)

Loveland, Colorado, 80538, United States

ACTIVE NOT RECRUITING

Delray Medical Center

Delray Beach, Florida, 33484, United States

WITHDRAWN

Cardiac & Vascular Institute Foundation

Gainesville, Florida, 32605, United States

ACTIVE NOT RECRUITING

Ascension St. Vincent's Hospital

Jacksonville, Florida, 32204, United States

ACTIVE NOT RECRUITING

Naples Community Hospital

Naples, Florida, 34102, United States

ACTIVE NOT RECRUITING

Sarasota Memorial Hospital

Sarasota, Florida, 34239, United States

ACTIVE NOT RECRUITING

Emory University

Atlanta, Georgia, 30308, United States

ACTIVE NOT RECRUITING

Piedmont Healthcare

Atlanta, Georgia, 30309, United States

ACTIVE NOT RECRUITING

Rush University Medical Center

Chicago, Illinois, 60612, United States

WITHDRAWN

Northshore University Health System

Glenview, Illinois, 60026, United States

ACTIVE NOT RECRUITING

St. Vincent Heart Center of Indiana

Indianapolis, Indiana, 46290, United States

WITHDRAWN

University of Kansas

Kansas City, Kansas, 66160, United States

ACTIVE NOT RECRUITING

Cardiovascular Research Institute of Kansas (CRIOK)

Wichita, Kansas, 67226, United States

ACTIVE NOT RECRUITING

Our Lady of the Lake Regional Medical Center

Baton Rouge, Louisiana, 70808, United States

ACTIVE NOT RECRUITING

Medstar Union Memorial Hospital

Baltimore, Maryland, 21218, United States

ACTIVE NOT RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

ACTIVE NOT RECRUITING

Brigham & Women's

Boston, Massachusetts, 02115, United States

WITHDRAWN

Henry Ford

Detroit, Michigan, 48202, United States

ACTIVE NOT RECRUITING

Minneapolis Heart

Minneapolis, Minnesota, 55407, United States

WITHDRAWN

Mayo Clinic

Rochester, Minnesota, 55905, United States

ACTIVE NOT RECRUITING

CentraCare

Saint Cloud, Minnesota, 56303, United States

ACTIVE NOT RECRUITING

Saint Luke's Kansas City

Kansas City, Missouri, 64111, United States

ACTIVE NOT RECRUITING

St. Patrick Hospital

Missoula, Montana, 59802, United States

WITHDRAWN

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

ACTIVE NOT RECRUITING

Morristown Medical Center

Morristown, New Jersey, 07962, United States

WITHDRAWN

Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08901, United States

ACTIVE NOT RECRUITING

University of Buffalo

Buffalo, New York, 14203, United States

ACTIVE NOT RECRUITING

Weill Cornell Medicine

New York, New York, 10007, United States

ACTIVE NOT RECRUITING

Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

WITHDRAWN

Novant Health and Vascular Institute

Charlotte, North Carolina, 28204, United States

ACTIVE NOT RECRUITING

The Christ Hospital

Cincinnati, Ohio, 45219, United States

ACTIVE NOT RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, 44122, United States

ACTIVE NOT RECRUITING

Mount Carmel East Hospital

Columbus, Ohio, 43123, United States

ACTIVE NOT RECRUITING

Oklahoma Heart Hospital

Oklahoma City, Oklahoma, 73120, United States

ACTIVE NOT RECRUITING

Oklahoma Heart Institute

Tulsa, Oklahoma, 74104, United States

ACTIVE NOT RECRUITING

UPMC Heart and Vascular Institute

Mechanicsburg, Pennsylvania, 17050, United States

ACTIVE NOT RECRUITING

Alleghany General Hospital

Pittsburgh, Pennsylvania, 15212, United States

WITHDRAWN

Saint Thomas Health

Nashville, Tennessee, 37205, United States

ACTIVE NOT RECRUITING

Austin Heart

Austin, Texas, 78705, United States

ACTIVE NOT RECRUITING

HCA Houston Healthcare Medical (SCRI)

Houston, Texas, 77004, United States

ACTIVE NOT RECRUITING

UT Memorial Hermann

Houston, Texas, 77030, United States

ACTIVE NOT RECRUITING

Intermountain Medical Center

Murray, Utah, 84107, United States

ACTIVE NOT RECRUITING

Sentara Norfolk

Norfolk, Virginia, 23507, United States

ACTIVE NOT RECRUITING

Carilion Roanoke Memorial Hospital

Roanoke, Virginia, 24014, United States

ACTIVE NOT RECRUITING

University of Washington Seattle

Seattle, Washington, 98195, United States

ACTIVE NOT RECRUITING

University of Wisconsin

Madison, Wisconsin, 53792-3248, United States

WITHDRAWN

The Prince Charles Hospital

Chermside, Queensland, 4032, Australia

ACTIVE NOT RECRUITING

Royal Prince Alfred Hospital

Camperdown, NSW2050, Australia

ACTIVE NOT RECRUITING

Laval University

Québec, Quebec, G1V 0A6, Canada

RECRUITING

St. Michael's

Toronto, M5B 1W8, Canada

RECRUITING

St. Pauls

Vancouver, V6E 1M7, Canada

RECRUITING

Shaare Zedek Medical Center

Jerusalem, 9103102, Israel

WITHDRAWN

Rabin Medical Center

Petah Tikva, 4941492, Israel

ACTIVE NOT RECRUITING

Sheba Medical Center

Ramat Gan, 5211401, Israel

WITHDRAWN

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

ACTIVE NOT RECRUITING

Rotterdam Erasmus MC

Rotterdam, 3015 CE, Netherlands

ACTIVE NOT RECRUITING

Saint Bartholomew's Medical Center

London, EC1A 7BE, United Kingdom

ACTIVE NOT RECRUITING

Saint Thomas Hospital

London, SE1 7EH, United Kingdom

ACTIVE NOT RECRUITING

Related Publications (1)

• Guerrero ME, Daniels DV, Makkar RR, Thourani VH, Asch FM, Pham M, Muhammad KI, Greenbaum AB, Vasquez A, Oldemeyer JB, Dahle TG, Rihal C, Morse MA, Rodriguez E, O'Neill BP, Russo M, Whisenant B, Yadav P, Yu X, Wang DD, Makar M, Baran DA, Mahoney P, Reddy G, Blanke P, Webb J; ENCIRCLE Trial Executive Committee and Study Investigators. Percutaneous transcatheter valve replacement in individuals with mitral regurgitation unsuitable for surgery or transcatheter edge-to-edge repair: a prospective, multicountry, single-arm trial. Lancet. 2025 Nov 29;406(10519):2541-2550. doi: 10.1016/S0140-6736(25)02073-2. Epub 2025 Oct 27.

  PMID: 41167201 DERIVED

MeSH Terms

Conditions

Mitral Valve Insufficiency

Condition Hierarchy (Ancestors)

Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases

Study Officials

• John Webb, MD

  St. Paul's Hospital

  PRINCIPAL INVESTIGATOR

• Mayra Guerrero, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• David Daniels, MD

  California Pacific Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Edwards TMTT Clinical Affairs

CONTACT

+1 (949) 250-2500; TMTT_Clinical@edwards.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 6, 2019
• Study Start: November 12, 2020
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2031
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); IL (3); AU (2); US (56); NL (2); GB (2)