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Mitral RegurgitationENCIRCLENCT04153292

The ENCIRCLE Trial

A study testing SAPIEN M3 valve and dock in people with Mitral Regurgitation and Mitral Valve Insufficiency, run by Edwards Lifesciences at 54 sites in 6 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

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
SAPIEN M3 valve and dock
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
786 participants
Where
54 sitesin 6 countries
Study dates
12 Nov 2020to 10 Oct 2031
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18 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.

Who cannot join

  • 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
Show all 28Show fewer
  • 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
  • Chronic obstructive pulmonary disease requiring home oxygen therapy or chronic outpatient oral steroid use
  • Renal insufficiency or receiving renal replacement therapy
  • Liver disease
  • Planned surgery within the next 12 months
  • Inability to tolerate or a medical condition precluding treatment with antithrombotic therapy, including heparin administration during the procedure
  • Active infection requiring current antibiotic therapy
  • Active SARS-CoV-2 infection (Coronavirus-19 [COVID-19]) or previously diagnosed with COVID-19 with sequelae that could confound endpoint assessments
  • Leukopenia, anemia, thrombocytopenia, history of bleeding diathesis or coagulopathy or hypercoagulable states
  • Refusal of blood products
  • Female who is pregnant or lactating
  • Estimated life expectancy <12 months due to non-cardiac conditions
  • Participating in another investigational drug or device study that has not reached its primary endpoint
  • Subject considered to be part of a vulnerable population

Trial locations and contacts

54 sites in 6 countries.

54 sites in 6 countries

United States44 sites

  • Emory University

    Atlanta, Georgia, 30308

  • Piedmont Healthcare

    Atlanta, Georgia, 30309

  • Austin Heart

    Austin, Texas, 78705

  • Medstar Union Memorial Hospital

    Baltimore, Maryland, 21218

  • Our Lady of the Lake Regional Medical Center

    Baton Rouge, Louisiana, 70808

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of Buffalo

    Buffalo, New York, 14203

  • Novant Health and Vascular Institute

    Charlotte, North Carolina, 28204

  • The Christ Hospital

    Cincinnati, Ohio, 45219

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44122

  • Mount Carmel East Hospital

    Columbus, Ohio, 43123

  • Henry Ford

    Detroit, Michigan, 48202

  • Cardiac & Vascular Institute Foundation

    Gainesville, Florida, 32605

  • Northshore University Health System

    Glenview, Illinois, 60026

  • HCA Houston Healthcare Medical (SCRI)

    Houston, Texas, 77004

  • UT Memorial Hermann

    Houston, Texas, 77030

  • Heart Center Hospital

    Huntsville, Alabama, 35801

  • Ascension St. Vincent's Hospital

    Jacksonville, Florida, 32204

  • University of Kansas

    Kansas City, Kansas, 66160

  • Saint Luke's Kansas City

    Kansas City, Missouri, 64111

  • Scripps Health

    La Jolla, California, 92037

  • Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • Good Samaritan Hospital

    Los Angeles, California, 90017

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Kaiser Sunset LA

    Los Angeles, California, 90071

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

    Loveland, Colorado, 80538

  • UPMC Heart and Vascular Institute

    Mechanicsburg, Pennsylvania, 17050

  • Intermountain Medical Center

    Murray, Utah, 84107

  • Naples Community Hospital

    Naples, Florida, 34102

  • Saint Thomas Health

    Nashville, Tennessee, 37205

  • Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08901

  • Weill Cornell Medicine

    New York, New York, 10007

  • Sentara Norfolk

    Norfolk, Virginia, 23507

  • Oklahoma Heart Hospital

    Oklahoma City, Oklahoma, 73120

  • Banner University Medical Center

    Phoenix, Arizona, 85006

  • Saint Josephs Hospital Medical Center Dignity Health

    Phoenix, Arizona, 85013

  • Carilion Roanoke Memorial Hospital

    Roanoke, Virginia, 24014

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • CentraCare

    Saint Cloud, Minnesota, 56303

  • California Pacific Medical Center

    San Francisco, California, 94109

  • Sarasota Memorial Hospital

    Sarasota, Florida, 34239

  • University of Washington Seattle

    Seattle, Washington, 98195

  • Oklahoma Heart Institute

    Tulsa, Oklahoma, 74104

  • Cardiovascular Research Institute of Kansas (CRIOK)

    Wichita, Kansas, 67226

Other trials in United States

Canada3 sites

  • Laval University

    Québec, Quebec, G1V 0A6

  • St. Michael's

    Toronto, M5B 1W8

  • St. Pauls

    Vancouver, V6E 1M7

Other trials in Canada

Australia2 sites

  • Royal Prince Alfred Hospital

    Camperdown, NSW2050

  • The Prince Charles Hospital

    Chermside, Queensland, 4032

Other trials in Australia

Netherlands2 sites

  • Leiden University Medical Center

    Leiden, 2333 ZA

  • Rotterdam Erasmus MC

    Rotterdam, 3015 CE

Other trials in Netherlands

United Kingdom2 sites

  • Saint Bartholomew's Medical Center

    London, EC1A 7BE

  • Saint Thomas Hospital

    London, SE1 7EH

Other trials in United Kingdom

Israel1 site

  • Rabin Medical Center

    Petah Tikva, 4941492

Other trials in Israel

About this study

Official title: SAPIEN M3 System Transcatheter Mitral Valve Replacement Via Transseptal Access

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.

Read the detailed description

This is a prospective single-arm, multicenter study.

Being tested
SAPIEN M3 valve and dock
Medical subject headings
Mitral Valve Insufficiency

What participants receive

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

  • SAPIEN M3 valve and dockDevice

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

Study groups in NCT04153292
Study groupRoleWhat they receive
TMVR - Main CohortExperimentalSubjects for whom commercially available surgical or transcatheter treatment options are deemed unsuitable will have transcatheter mitral valve replacement (TMVR).
Receives: Device: SAPIEN M3 valve and dock
TMVR - Failed TEER RegistryExperimentalSubjects who have had an attempted but failed transcatheter edge-to-edge repair (TEER) procedure will have TMVR.
Receives: Device: SAPIEN M3 valve and dock
TMVR - MAC RegistryExperimentalSubjects with mitral annular calcification (MAC) will have TMVR.
Receives: Device: SAPIEN M3 valve and dock

What is being measured

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

  1. Non-hierarchical composite of death and heart failure rehospitalization

    Number of subjects with death and/or heart failure rehospitalization

    Measured: 1 year

Secondary outcomes (4)

  1. Improvement in NYHA functional class compared to baseline

    New York Heart Association (NYHA) functional classification of heart failure is based on how much a patient is limited during physical activity. The rating ranges from I-IV. I = no limitations of physical activity; II = slight limitations of physical activity, ordinary physical activity results in fatigue, palpitation, shortness of breath; III = marked limitations of physical activity, less than ordinary activity causes fatigue, palpitation, or shortness of breath; IV = unable to carry on any physical activity without discomfort, symptoms of heart failure at rest.

    Measured: 1 year

  2. Improvement in KCCQ Overall Score compared to baseline

    The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. An overall summary score can be derived from the physical function, symptom (frequency and severity), social function and quality of life domains. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.

    Measured: 1 year

  3. Improvement in MR compared to baseline

    Number of subjects with improved MR compared to baseline

    Measured: 1 year

  4. Decrease in LVEDVi compared to baseline

    Number of subjects with decreased left ventricular end-diastolic volume index (LVEDVi) compared to baseline

    Measured: 1 year

Timeline

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

  1. First posted6 Nov 2019
  2. Study start12 Nov 2020
  3. Primary completion10 Oct 2027 (estimated)
  4. Study completion10 Oct 2031 (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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
786 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04153292
Sponsor's protocol ID
2018-19
Acronym
ENCIRCLE
Status last verified
Sep 2026
First submitted
4 Nov 2019
Last updated
6 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 41167201

Questions about this trial

What is this clinical trial studying?

A study testing SAPIEN M3 valve and dock in people with Mitral Regurgitation and Mitral Valve Insufficiency, run by Edwards Lifesciences at 54 sites in 6 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 28 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 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 54 sites in United States, Canada, Australia, Netherlands, United Kingdom and 1 more country. 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?

Non-hierarchical composite of death and heart failure rehospitalization (time frame: 1 year). 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 NCT04153292, which also lists 1 linked publication.

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 6 Oct 2026.

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The ENCIRCLE Trial (NCT04153292) | AzTrials