Mitral Valve Edge-to-Edge Reconstruction in Patients With Exercise-Induced Severe Secondary Mitral Regurgitation and Heart Failure
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 246
- 试验地点
- 2
- 主要终点
- 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.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Guideline-directed medical therapy (GDMT)
Participants receive GDMT according to current heart failure and valvular heart disease guidelines.
干预措施: Guideline-Directed Medical Therapy (GDMT) (Other)
Guideline-directed medical therapy (GDMT) + mitral valve TEER
Participants receive GDMT plus mitral valve TEER
干预措施: Mitral valve TEER (Procedure)
结局指标
主要结局
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.
时间窗: 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.
次要结局
- Number of participants with myocardial infarction(12 months)
- Number of participants with cardiovascular death(12 months)
- Number of participants with heart failure hospitalization(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)
- Change from baseline in 36-Item Short Form Survey (SF-36) score(Baseline, 1, 6, and 12 months)
- Number of participants requiring mitral valve surgery(12 months)
- Change from baseline in secondary mitral regurgitation severity grade according to the American Society of Echocardiography (ASE) criteria at rest(Baseline, 1, 6, and 12 months)
- Change from baseline in left ventricular end-systolic volume index (LVESVi)(Baseline, 1, 6, and 12 months)
- Change from baseline in left ventricular end-diastolic volume index (LVEDVi)(Baseline, 1, 6, and 12 months)
- Change from baseline in pulmonary artery systolic pressure (SPAP)(Baseline, 1, 6, and 12 months)
- Change from baseline in New York Heart Association (NYHA) functional class(Baseline, 1, 6, and 12 months)
- Change from baseline in six-minute walk test (6MWT) distance(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)(Baseline, 1, 6, and 12 months)
研究者
Christian Schulze
Director of Department of Internal Medicine I at Jena University Hospital and Professor of Medicine at Friedrich Schiller University Jena
Jena University Hospital