The ENCIRCLE Trial

NCT ID: NCT04153292

Last Updated: 2026-01-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

900 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-12

Study Completion Date

2031-02-28

Brief Summary

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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.

Detailed Description

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This is a prospective single-arm, multicenter study.

Conditions

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Mitral Regurgitation Mitral Valve Insufficiency

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TMVR - Main Cohort

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

Group Type EXPERIMENTAL

SAPIEN M3 valve and dock

Intervention Type DEVICE

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

TMVR - Failed TEER Registry

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

Group Type EXPERIMENTAL

SAPIEN M3 valve and dock

Intervention Type DEVICE

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

TMVR - MAC Registry

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

Group Type EXPERIMENTAL

SAPIEN M3 valve and dock

Intervention Type DEVICE

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

Interventions

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SAPIEN M3 valve and dock

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

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

1. 18 years of age or older
2. MR ≥ 3+
3. NYHA functional class ≥ II
4. Per the Heart Team, commercially available surgical or transcatheter treatment options are deemed unsuitable due to clinical, anatomic or technical considerations.
5. 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.
6. 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.

Exclusion Criteria

1. Mitral/cardiac anatomy that would preclude appropriate delivery and deployment of the SAPIEN M3 dock or valve
2. Inappropriate anatomy for femoral introduction and delivery of the SAPIEN M3 dock and valve
3. Presence of any device that will contact or interfere with the SAPIEN M3 System during delivery or after implantation
4. Left ventricular ejection fraction \<25%
5. Severe right ventricular dysfunction
6. Need for aortic, tricuspid or pulmonic valve intervention within the next 12 months
7. History of heart transplant
8. Cardiac imaging evidence of intracardiac mass, thrombus or vegetation
9. Active bacterial endocarditis within 180 days of the procedure
10. Hemodynamic instability requiring inotropic or mechanical support within 30 days of the procedure
11. Myocardial infarction within 30 days of the procedure
12. Clinically significant untreated coronary artery disease requiring revascularization
13. Any percutaneous cardiovascular intervention, cardiovascular surgery, or carotid surgery within 30 days of the procedure
14. Stroke or transient ischemic attack within 90 days of the procedure
15. Irreversible, severe pulmonary hypertension
16. Chronic obstructive pulmonary disease requiring home oxygen therapy or chronic outpatient oral steroid use
17. Renal insufficiency or receiving renal replacement therapy
18. Liver disease
19. Planned surgery within the next 12 months
20. Inability to tolerate or a medical condition precluding treatment with antithrombotic therapy, including heparin administration during the procedure
21. Active infection requiring current antibiotic therapy
22. Active SARS-CoV-2 infection (Coronavirus-19 \[COVID-19\]) or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments
23. Leukopenia, anemia, thrombocytopenia, history of bleeding diathesis or coagulopathy or hypercoagulable states
24. Refusal of blood products
25. Female who is pregnant or lactating
26. Estimated life expectancy \<12 months due to non-cardiac conditions
27. Participating in another investigational drug or device study that has not reached its primary endpoint
28. Subject considered to be part of a vulnerable population
Minimum Eligible Age

18 Years

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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John Webb, MD

Role: PRINCIPAL_INVESTIGATOR

St. Paul's Hospital

Mayra Guerrero, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

David Daniels, MD

Role: PRINCIPAL_INVESTIGATOR

California Pacific Medical Center

Locations

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Heart Center Hospital

Huntsville, Alabama, United States

Site Status ACTIVE_NOT_RECRUITING

Banner University Medical Center

Phoenix, Arizona, United States

Site Status ACTIVE_NOT_RECRUITING

Saint Josephs Hospital Medical Center Dignity Health

Phoenix, Arizona, United States

Site Status ACTIVE_NOT_RECRUITING

TMC Healthcare

Tucson, Arizona, United States

Site Status WITHDRAWN

Scripps Health

La Jolla, California, United States

Site Status ACTIVE_NOT_RECRUITING

Good Samaritan Hospital

Los Angeles, California, United States

Site Status ACTIVE_NOT_RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, United States

Site Status ACTIVE_NOT_RECRUITING

Kaiser Sunset LA

Los Angeles, California, United States

Site Status ACTIVE_NOT_RECRUITING

Saint Joseph Hospital

Orange, California, United States

Site Status WITHDRAWN

California Pacific Medical Center

San Francisco, California, United States

Site Status ACTIVE_NOT_RECRUITING

UC Health Northern Colorado (Medical Center of the Rockies)

Loveland, Colorado, United States

Site Status ACTIVE_NOT_RECRUITING

Delray Medical Center

Delray Beach, Florida, United States

Site Status WITHDRAWN

Cardiac & Vascular Institute Foundation

Gainesville, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

Ascension St. Vincent's Hospital

Jacksonville, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

Naples Community Hospital

Naples, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

Sarasota Memorial Hospital

Sarasota, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

Emory University

Atlanta, Georgia, United States

Site Status ACTIVE_NOT_RECRUITING

Piedmont Healthcare

Atlanta, Georgia, United States

Site Status ACTIVE_NOT_RECRUITING

Rush University Medical Center

Chicago, Illinois, United States

Site Status WITHDRAWN

Northshore University Health System

Glenview, Illinois, United States

Site Status ACTIVE_NOT_RECRUITING

St. Vincent Heart Center of Indiana

Indianapolis, Indiana, United States

Site Status WITHDRAWN

University of Kansas

Kansas City, Kansas, United States

Site Status ACTIVE_NOT_RECRUITING

Cardiovascular Research Institute of Kansas (CRIOK)

Wichita, Kansas, United States

Site Status ACTIVE_NOT_RECRUITING

Our Lady of the Lake Regional Medical Center

Baton Rouge, Louisiana, United States

Site Status ACTIVE_NOT_RECRUITING

Medstar Union Memorial Hospital

Baltimore, Maryland, United States

Site Status ACTIVE_NOT_RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status ACTIVE_NOT_RECRUITING

Brigham & Women's

Boston, Massachusetts, United States

Site Status WITHDRAWN

Henry Ford

Detroit, Michigan, United States

Site Status ACTIVE_NOT_RECRUITING

Minneapolis Heart

Minneapolis, Minnesota, United States

Site Status WITHDRAWN

Mayo Clinic

Rochester, Minnesota, United States

Site Status ACTIVE_NOT_RECRUITING

CentraCare

Saint Cloud, Minnesota, United States

Site Status ACTIVE_NOT_RECRUITING

Saint Luke's Kansas City

Kansas City, Missouri, United States

Site Status ACTIVE_NOT_RECRUITING

St. Patrick Hospital

Missoula, Montana, United States

Site Status WITHDRAWN

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status ACTIVE_NOT_RECRUITING

Morristown Medical Center

Morristown, New Jersey, United States

Site Status WITHDRAWN

Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Site Status ACTIVE_NOT_RECRUITING

University of Buffalo

Buffalo, New York, United States

Site Status ACTIVE_NOT_RECRUITING

Weill Cornell Medicine

New York, New York, United States

Site Status ACTIVE_NOT_RECRUITING

Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status WITHDRAWN

Novant Health and Vascular Institute

Charlotte, North Carolina, United States

Site Status ACTIVE_NOT_RECRUITING

The Christ Hospital

Cincinnati, Ohio, United States

Site Status ACTIVE_NOT_RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status ACTIVE_NOT_RECRUITING

Mount Carmel East Hospital

Columbus, Ohio, United States

Site Status ACTIVE_NOT_RECRUITING

Oklahoma Heart Hospital

Oklahoma City, Oklahoma, United States

Site Status ACTIVE_NOT_RECRUITING

Oklahoma Heart Institute

Tulsa, Oklahoma, United States

Site Status ACTIVE_NOT_RECRUITING

UPMC Heart and Vascular Institute

Mechanicsburg, Pennsylvania, United States

Site Status ACTIVE_NOT_RECRUITING

Alleghany General Hospital

Pittsburgh, Pennsylvania, United States

Site Status WITHDRAWN

Saint Thomas Health

Nashville, Tennessee, United States

Site Status ACTIVE_NOT_RECRUITING

Austin Heart

Austin, Texas, United States

Site Status ACTIVE_NOT_RECRUITING

HCA Houston Healthcare Medical (SCRI)

Houston, Texas, United States

Site Status ACTIVE_NOT_RECRUITING

UT Memorial Hermann

Houston, Texas, United States

Site Status ACTIVE_NOT_RECRUITING

Intermountain Medical Center

Murray, Utah, United States

Site Status ACTIVE_NOT_RECRUITING

Sentara Norfolk

Norfolk, Virginia, United States

Site Status ACTIVE_NOT_RECRUITING

Carilion Roanoke Memorial Hospital

Roanoke, Virginia, United States

Site Status ACTIVE_NOT_RECRUITING

University of Washington Seattle

Seattle, Washington, United States

Site Status ACTIVE_NOT_RECRUITING

University of Wisconsin

Madison, Wisconsin, United States

Site Status WITHDRAWN

The Prince Charles Hospital

Chermside, Queensland, Australia

Site Status ACTIVE_NOT_RECRUITING

Royal Prince Alfred Hospital

Camperdown, , Australia

Site Status ACTIVE_NOT_RECRUITING

Laval University

Québec, Quebec, Canada

Site Status RECRUITING

St. Michael's

Toronto, , Canada

Site Status RECRUITING

St. Pauls

Vancouver, , Canada

Site Status RECRUITING

Shaare Zedek Medical Center

Jerusalem, , Israel

Site Status WITHDRAWN

Rabin Medical Center

Petah Tikva, , Israel

Site Status ACTIVE_NOT_RECRUITING

Sheba Medical Center

Ramat Gan, , Israel

Site Status WITHDRAWN

Leiden University Medical Center

Leiden, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

Rotterdam Erasmus MC

Rotterdam, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

Saint Bartholomew's Medical Center

London, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

Saint Thomas Hospital

London, , United Kingdom

Site Status ACTIVE_NOT_RECRUITING

Countries

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United States Australia Canada Israel Netherlands United Kingdom

Central Contacts

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Edwards THV Clinical Affairs

Role: CONTACT

+1 (949) 250-2500

References

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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.

Reference Type DERIVED
PMID: 41167201 (View on PubMed)

Other Identifiers

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2018-19

Identifier Type: -

Identifier Source: org_study_id

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