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

Official title

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

Overview

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.

Interventions

• Other Guideline-Directed Medical Therapy (GDMT)
  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.
• Procedure Mitral valve TEER
  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 stan

Primary outcome measures

• 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]

Secondary outcome measures (12)

• Number of participants with cardiovascular death [Time frame: 12 months]
• Number of participants with heart failure hospitalization [Time frame: 12 months]
• Number of participants with myocardial infarction [Time frame: 12 months]
• Number of participants with stroke [Time frame: 12 months]
• Change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) score [Time frame: Baseline, 1, 6, and 12 months]
• Change from baseline in 36-Item Short Form Survey (SF-36) score [Time frame: Baseline, 1, 6, and 12 months]
• Number of participants requiring mitral valve surgery [Time frame: 12 months]
• 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]
• Change from baseline in left ventricular end-systolic volume index (LVESVi) [Time frame: Baseline, 1, 6, and 12 months]
• Change from baseline in left ventricular end-diastolic volume index (LVEDVi) [Time frame: Baseline, 1, 6, and 12 months]
• Change from baseline in pulmonary artery systolic pressure (SPAP) [Time frame: Baseline, 1, 6, and 12 months]
• Change from baseline in New York Heart Association (NYHA) functional class [Time frame: Baseline, 1, 6, and 12 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Germany · 2 centers

• Department of Cardiology, Pneumology and Vascular Medicine University Hospital Düsseldorf — Düsseldorf
• Department of Internal Medicine I (KIM I) Division of Cardiology, Angiology and Intensive — Jena

Identifiers

NCT: NCT07709208 · ZKSJ0169_MARCER

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗