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

NCT07709208 | Not Yet Recruiting DMC

• 1 other identifier: ZKSJ0169_MARCER
• Study Type: interventional
• Target: 246
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Heart Failure - NYHA II - IV; Mitral Regurgitation Functional

Keywords

secondary mitral regurgitation; exercise-induced severe mitral regurgitation; dynamic mitral regurgitation

Outcome Measures

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.

  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: 1. time to all-cause mortality, days 2. time to first heart failure hospitalization, days 3. secondary mitral regurgitation progression (3+/4+) at rest and 4. 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.

  12 months

Secondary Outcomes (14)

• Number of participants with cardiovascular death

  12 months

• Number of participants with heart failure hospitalization

  12 months

• Number of participants with myocardial infarction

  12 months

• Number of participants with stroke

  12 months

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

  Baseline, 1, 6, and 12 months

Other Outcomes (6)

• Number of participants with all-cause mortality

  12 months

• Number of participants with procedure-related complications during TEER

  During procedure

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

  12 months

Study Arms (2)

Guideline-directed medical therapy (GDMT)

ACTIVE COMPARATOR

Participants receive GDMT according to current heart failure and valvular heart disease guidelines.

Other: Guideline-Directed Medical Therapy (GDMT)

Guideline-directed medical therapy (GDMT) + mitral valve TEER

EXPERIMENTAL

Participants receive GDMT plus mitral valve TEER

Procedure: Mitral valve TEER

Interventions

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.

Guideline-directed medical therapy (GDMT)

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.

Guideline-directed medical therapy (GDMT) + mitral valve TEER

Eligibility Criteria

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

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jena University Hospital: lead

Study Sites (2)

Department of Cardiology, Pneumology and Vascular Medicine University Hospital Düsseldorf

Düsseldorf, Germany

Location

Department of Internal Medicine I (KIM I) Division of Cardiology, Angiology and Intensive Medical Care Jena University Hospital

Jena, Germany

Location

Study Officials

• Christian Schulze, Prof. Dr.

  University Hospital Jena

  STUDY DIRECTOR

• Maximilian Spieker, PD Dr.

  Heinrich-Heine University, Duesseldorf

  STUDY DIRECTOR

Central Study Contacts

Christian Schulze, Prof. Dr.

CONTACT

+49 3641 9 324101; christian.schulze@med.uni-jena.de

Maximilian Spieker, PD Dr.

CONTACT

+49 211 / 81 18914; maximilian.spieker@med.uni-duesseldorf.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Internal Medicine I at Jena University Hospital and Professor of Medicine at Friedrich Schiller University Jena

Study Record Dates

• First Submitted: June 30, 2026
• First Posted: July 16, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2030
• Last Updated: July 16, 2026

Record last verified: 2026-07

Locations

DE (2)