Heart Failure - NYHA II - IVMARCERNCT07709208
Mitral Valve Edge-to-Edge Repair in Patients With Exercise-Induced Severe Mitral Regurgitation
A study testing Guideline-Directed Medical Therapy (GDMT) and Mitral valve TEER in people with Heart Failure - NYHA II - IV and Mitral Regurgitation Functional, run by Jena University Hospital at 2 sites in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure - NYHA II - IV, Mitral Regurgitation Functional
- What is being tested?
- Guideline-Directed Medical Therapy (GDMT) and Mitral valve TEER
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 246 participants
- Where
- 2 sitesGermany
- Study dates
- 16 Sep 2026to Jun 2030
- Phase
- Interventional
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
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Germany2 sites, 2 recruiting
- Not yet recruiting
Department of Cardiology, Pneumology and Vascular Medicine University Hospital Düsseldorf
Düsseldorf
Maximilian Spieker, PD Dr., +49 211 / 81 18914, maximilian.spieker@med.uni-duesseldorf.de
Maximilian Spieker, PD Dr.
- Recruiting
Department of Internal Medicine I (KIM I) Division of Cardiology, Angiology and Intensive Medical Care Jena University Hospital
Jena
Christian Schulze, Prof. Dr., +49 3641 9 324101, christian.schulze@med.uni-jena.de
Christian Schulze, Prof. Dr.
About this study
Official title: Mitral Valve Edge-to-Edge Reconstruction in Patients With Exercise-Induced Severe Secondary Mitral Regurgitation and Heart Failure
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:
Read more
- 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.
- Being tested
- Guideline-Directed Medical Therapy (GDMT), Mitral valve TEER
- Keywords
- secondary mitral regurgitation, exercise-induced severe mitral regurgitation, dynamic mitral regurgitation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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 TEERProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Guideline-directed medical therapy (GDMT) | Active comparator | Participants receive GDMT according to current heart failure and valvular heart disease guidelines. Receives: Other: Guideline-Directed Medical Therapy (GDMT) |
| Guideline-directed medical therapy (GDMT) + mitral valve TEER | Experimental | Participants receive GDMT plus mitral valve TEER Receives: Procedure: Mitral valve TEER |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- 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.
Measured: 12 months
Secondary outcomes (14)
Number of participants with cardiovascular death
Death due to cardiovascular causes during follow-up.
Measured: 12 months
Number of participants with heart failure hospitalization
Hospitalization due to worsening heart failure requiring inpatient treatment.
Measured: 12 months
Number of participants with myocardial infarction
Occurrence of myocardial infarction during follow-up.
Measured: 12 months
Number of participants with stroke
Occurrence of ischemic or hemorrhagic stroke during follow-up.
Measured: 12 months
Change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) score
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.
Measured: Baseline, 1, 6, and 12 months
Change from baseline in 36-Item Short Form Survey (SF-36) score
General health-related quality of life assessed using the SF-36 questionnaire, including physical and mental component summary scores.
Measured: Baseline, 1, 6, and 12 months
Number of participants requiring mitral valve surgery
Occurrence of surgical mitral valve intervention during follow-up.
Measured: 12 months
Change from baseline in secondary mitral regurgitation severity grade according to the American Society of Echocardiography (ASE) criteria at rest
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).
Measured: Baseline, 1, 6, and 12 months
Change from baseline in left ventricular end-systolic volume index (LVESVi)
Left ventricular end-systolic volume index measured by echocardiography.
Measured: Baseline, 1, 6, and 12 months
Change from baseline in left ventricular end-diastolic volume index (LVEDVi)
Left ventricular end-diastolic volume index measured by echocardiography.
Measured: Baseline, 1, 6, and 12 months
Change from baseline in pulmonary artery systolic pressure (SPAP)
Pulmonary artery systolic pressure assessed by echocardiography.
Measured: Baseline, 1, 6, and 12 months
Change from baseline in New York Heart Association (NYHA) functional class
Heart failure functional status assessed using NYHA classification.
Measured: Baseline, 1, 6, and 12 months
Change from baseline in six-minute walk test (6MWT) distance
Exercise capacity assessed using the six-minute walk test.
Measured: Baseline, 1, 6, and 12 months
Change from baseline in NT-proBNP (N-terminal pro Brain natriuretic peptide, pg/ml) (alternatively calculated from BNP, Brain natriuretic peptide, pg/ml)
Heart failure biomarkers measured in blood samples.
Measured: Baseline, 1, 6, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2026
- Study start16 Sep 2026
- Primary completionJun 2029 (estimated)
- Study completionJun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure - NYHA II - IVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 246 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jena University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christian Schulze, Jena University Hospital
- Investigators
- Christian Schulze, Prof. Dr., Study director, University Hospital JenaMaximilian Spieker, PD Dr., Study director, Heinrich-Heine University, Duesseldorf
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07709208
- Sponsor's protocol ID
- ZKSJ0169_MARCER
- Acronym
- MARCER
- Status last verified
- Oct 2026
- First submitted
- 30 Jun 2026
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No