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NCT Number: NCT07709208

Mitral Valve Edge-to-Edge Repair in Patients With Exercise-Induced Severe Mitral Regurgitation

The goal of this clinical trial is to learn whether mitral valve transcatheter edge-to-edge repair (TEER) in addition to guideline-directed medical therapy (GDMT) can improve clinical outcomes and symptoms in heart failure patients with non-severe secondary mitral regurgitation (SMR) at rest and exercise-induced severe SMR.

The main questions it aims to answer are:

* Does mitral valve TEER in addition to GDMT lead to better overall clinical outcomes than GDMT alone in patients with heart failure and exercise-induced severe SMR? * Does mitral valve TEER reduce the risk of death, heart failure hospitalization, or worsening SMR during 12 months of follow-up compared with GDMT alone? * Does mitral valve TEER improve patients' quality of life compared with GDMT alone?

Participants will:

* Undergo screening assessments to confirm eligibility for the study. * Be randomly assigned to receive either GDMT alone or GDMT plus mitral valve TEER. * Attend follow-up visits at approximately 3 time points during a 12-month follow-up period. * Undergo clinical evaluations that are routinely performed in patients with heart failure and SMR, including assessment of symptoms, functional status, and cardiac function.

The patients' echocardiographic data will undergo an additional centralized assessment by an independent Core Laboratory.

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Key information

Conditions

Heart Failure - NYHA II - IV Mitral Regurgitation Functional

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department of Cardiology, Pneumology and Vascular Medicine University Hospital Düsseldorf, Düsseldorf, Germany

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Mild-to-moderate (1+/2+) SMR at rest
  • Exacerbation of SMR to exercise-induced severe (3+/4+) SMR defined by at least one of the following:
  • 40 mm^2 EROA (30 mm^2 under low-flow condition) or
  • regurgitant volume ≥60 mL (45 mL under low-flow condition) or
  • regurgitant fraction ≥40% or
  • increase by 13 mm^2 EROA from rest to exercise
  • Increase in natriuretic peptides defined as NT-proBNP:
  • >250 pg/ml (Sinus rhythm) or
  • >600 pg/ml (Atrial fibrillation) or
  • HF hospitalization within 12 months prior to screening (defined as HF listed as the major reason for hospitalization)
  • NYHA class II-IV
  • Stable HF medication regimen (GDMT) for at least 30 days prior to index procedure
  • Patient deemed appropriate candidate for TEER by the local multidisciplinary heart team
  • Age ≥ 18 years old
  • Written Informed consent

Exclusion criteria

  • Hospitalization in past three months due to myocardial infarction, coronary artery bypass graft surgery, and/or unstable angina
  • LVEDD >70 mm
  • LVEF <20%
  • Evidence of transient ischemic attack or stroke within three months prior to intervention
  • Percutaneous coronary intervention in the last 30 days
  • Subjects expected to require any cardiac surgery, including surgery for coronary artery disease or for pulmonic, aortic, or tricuspid valve disease within one year
  • Presence of primary renal dysfunction or significantly compromised renal function (eGFR <30 ml/min)
  • Severe right ventricular failure
  • Severe aortic stenosis (aortic valve area <1.0 cm^2) or aortic regurgitation
  • Hemodynamic instability requiring inotropic support or mechanical heart circulatory support
  • Presence of a mechanical mitral heart valve, mitral bioprosthetic valve or mitral annuloplasty ring, indication for cardiac resynchronization therapy
  • Echocardiographic evidence of intracardiac mass, thrombus, or vegetation
  • Active endocarditis or infections requiring current antibiotic therapy
  • Hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, or any other structural heart disease causing HF other than SMR
  • Inability to exercise
  • Pregnancy or planning pregnancy within next12 months
  • Life expectancy <12 months (judgement of investigator)
  • Anticipated need of left ventricular assist device within next 12 months
  • Participation in another interventional clinical trial (primary endpoint not yet reached) during this trial or within 30 days prior to enrolment into this trial
  • Previous participation in this trial

Treatment and study plan

Guideline-Directed Medical Therapy (GDMT)

Other

Participants receive guideline-directed medical therapy (GDMT) for heart failure and secondary mitral regurgitation (SMR) according to current clinical practice guidelines. Medical treatment may include optimized pharmacological therapy such as beta-blockers, ACE inhibitors/ARBs/ARNI, mineralocorticoid receptor antagonists, diuretics, SGLT2-inhibitors and other indicated medications. Treatment is adjusted based on clinical status and treating physician judgment.

Mitral valve TEER

Procedure

Participants receive guideline-directed medical therapy (GDMT) for heart failure and secondary mitral regurgitation (SMR) according to current clinical practice guidelines in combination with TEER of the mitral valve using the PASCAL Precision system (Edwards Lifesciences Sàrl). The procedure is performed via a minimally invasive transcatheter approach through femoral venous access to reduce SMR. Guideline-directed medical therapy is continued and optimized throughout follow-up according to standard of care.

Primary outcomes

  1. Four-step hierarchical composite primary endpoint; win ratio based on the following parameters: time to all-cause mortality at 12 months, time to first HF hospitalization, SMR progression (3+/4+) at rest, change in KCCQ score from baseline to 12 months.

    Time frame: 12 months

    The primary outcome is a single aggregated, unitless win ratio based on a four-step hierarchical composite primary endpoint at 12 months. Each patient in the GDMT+mitral valve TEER group will be compared with each patient in the GDMT group with respect to the following parameters in the following order:

    • time to all-cause mortality, days
    • time to first heart failure hospitalization, days
    • secondary mitral regurgitation progression (3+/4+) at rest and
    • change in KCCQ score from baseline to 12 months, where higher improvement or less deterioration wins; differences between patients less than 5 points are treated as ties (i.e. a between-patient threshold of 5 pts., KCCQ-values range from 0 to 100, higher values indicating better health).

    For each pairwise comparison, the first non-tied component determines a win for one group or a tie. The win ratio is the number of wins in the GDMT+ mitral valve TEER group divided by the number of wins in the GDMT group.

Secondary outcomes

  1. Number of participants with cardiovascular death

    Time frame: 12 months

    Death due to cardiovascular causes during follow-up.

  2. Number of participants with heart failure hospitalization

    Time frame: 12 months

    Hospitalization due to worsening heart failure requiring inpatient treatment.

  3. Number of participants with myocardial infarction

    Time frame: 12 months

    Occurrence of myocardial infarction during follow-up.

  4. Number of participants with stroke

    Time frame: 12 months

    Occurrence of ischemic or hemorrhagic stroke during follow-up.

  5. Change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) score

    Time frame: Baseline, 1, 6, and 12 months

    Health-related quality of life assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ): scores range from 0 to 100, with higher scores indicating better health status.

  6. Change from baseline in 36-Item Short Form Survey (SF-36) score

    Time frame: Baseline, 1, 6, and 12 months

    General health-related quality of life assessed using the SF-36 questionnaire, including physical and mental component summary scores.

  7. Number of participants requiring mitral valve surgery

    Time frame: 12 months

    Occurrence of surgical mitral valve intervention during follow-up.

  8. Change from baseline in secondary mitral regurgitation severity grade according to the American Society of Echocardiography (ASE) criteria at rest

    Time frame: Baseline, 1, 6, and 12 months

    Secondary mitral regurgitation severity will be assessed at rest by transthoracic echocardiography according to the American Society of Echocardiography (ASE) criteria using a 4-grade scale: Grade 1 (mild), Grade 2 (moderate), Grade 3 (moderate-to-severe), and Grade 4 (severe). Severity grading will be based on an integrated assessment of echocardiographic parameters, including effective regurgitant orifice area (EROA), regurgitant volume (RVol), and regurgitant fraction (RF).

  9. Change from baseline in left ventricular end-systolic volume index (LVESVi)

    Time frame: Baseline, 1, 6, and 12 months

    Left ventricular end-systolic volume index measured by echocardiography.

  10. Change from baseline in left ventricular end-diastolic volume index (LVEDVi)

    Time frame: Baseline, 1, 6, and 12 months

    Left ventricular end-diastolic volume index measured by echocardiography.

  11. Change from baseline in pulmonary artery systolic pressure (SPAP)

    Time frame: Baseline, 1, 6, and 12 months

    Pulmonary artery systolic pressure assessed by echocardiography.

  12. Change from baseline in New York Heart Association (NYHA) functional class

    Time frame: Baseline, 1, 6, and 12 months

    Heart failure functional status assessed using NYHA classification.

  13. Change from baseline in six-minute walk test (6MWT) distance

    Time frame: Baseline, 1, 6, and 12 months

    Exercise capacity assessed using the six-minute walk test.

  14. Change from baseline in NT-proBNP (N-terminal pro Brain natriuretic peptide, pg/ml) (alternatively calculated from BNP, Brain natriuretic peptide, pg/ml)

    Time frame: Baseline, 1, 6, and 12 months

    Heart failure biomarkers measured in blood samples.

Other outcomes

  1. Number of participants with all-cause mortality

    Time frame: 12 months

    Death from any cause during the study follow-up period.

  2. Number of participants with procedure-related complications during TEER

    Time frame: During procedure

    Complications occurring during or immediately after the TEER procedure.

  3. Number of participants requiring non-elective cardiovascular surgery for device-related complications

    Time frame: 12 months

    Emergency or unplanned cardiovascular surgery related to the device or procedure.

  4. Number of participants with endocarditis

    Time frame: 12 months

    Occurrence of infective endocarditis during follow-up.

  5. Number of participants with major bleeding (TIMI criteria)

    Time frame: 12 months

    Major bleeding events defined according to the Thrombolysis In Myocardial Infarction (TIMI) bleeding criteria, including fatal bleeding, intracranial hemorrhage, or clinically significant bleeding associated with a drop in hemoglobin ≥5 g/dL or hematocrit ≥15%.

  6. Number of participants with cardiac tamponade

    Time frame: 12 months

    Occurrence of pericardial tamponade.

Study contacts

Contact information is provided by the study sponsor or research team.

Christian Schulze, Prof. Dr.

CONTACT

[email protected]

+49 3641 9 324101

Maximilian Spieker, PD Dr.

CONTACT

[email protected]

+49 211 / 81 18914

Sponsors and collaborators

Lead sponsor

Jena University Hospital

Other

Registry information

Official study title

Mitral Valve Edge-to-Edge Reconstruction in Patients With Exercise-Induced Severe Secondary Mitral Regurgitation and Heart Failure

Acronym: MARCER

Important dates

Study start
2026
Primary completion
2029
Study completion
2030
First posted
Jul 16, 2026
Registry last updated
Jul 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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