Mitral Regurgitation Treatment in Advanced Heart Failure

Study Overview
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Brief Summary
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MITRADVANCE-HF is a prospective, randomized, parallel-controlled, open-label, multicentre study trial enrolling patients with SMR and advanced HF on maximally tolerated standard of care therapies for HF according to the most recent guidelines. Enrolled patients will be randomly assigned, in a 1:1 ratio, to a device arm consisting of MitraClip therapy added to optimal medical therapy (OMT) or a control arm of OMT alone. Approximately 20 Italian high-volume centres will be involved. Enrolment duration will be of 24 months. Follow-up visit will be performed at 3, 6, and 12 months. Primary end-point was the absolute change in overall KCCQ summary score (KCCQ-OS) from baseline to 3 months follow-up.

Detailed Description
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There are no studies comparing MitraClip and optimal medical therapy (OMT) in patients with advanced heart failure (HF). The aim of this study is to assess the effects of MitraClip on health status, measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ), in patients with secondary mitral regurgitation (SMR) and advanced HF. Secondary aims are to evaluate persistence of such benefits up to 1 year as well as changes in survival, HF hospitalization, functional status, symptoms, echocardiographic parameters, and further optimization in medical therapies. MITRADVANCE-HF is a prospective, randomized, parallel-controlled, open-label, multicenter study trial enrolling patients with SMR and advanced HF on maximally tolerated standard of care therapies for HF according to the most recent guidelines. Enrolled patients will be randomly assigned, in a 1:1 ratio, to a device arm consisting of MitraClip therapy added to optimal medical therapy (OMT) or a control arm of OMT alone. Primary end-point was the absolute change in overall KCCQ summary score (KCCQ-OS) from baseline to 3 months follow-up. A total of 172 patients should be recruited (86 in the device arm and 86 in the control arm. Approximately 20 Italian centers are involved. All screened patients need to be approved by an eligibility committee before randomization. Visit 0 will be performed before randomization. A discharge visit will be performed in patients randomized to the device arm. Visit 1, 2 and 3 will be performed at 3, 6 and 12 months after the randomization in both arms. Transthoracic echocardiography performed during Visit 0, 1, 2 and 3 will be collected and analyzed by an independent Core Laboratory. Adverse events will be adjudicated by an independent committee. Enrolment duration will be of 24 months. The primary completion is the date when the last enrolled subject is assessed for the collection of the primary endpoint. The end of the study is when the last enrolled subject has completed the last follow-up visit.

Official Title
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Mitral Regurgitation Treatment in Advanced Heart Failure

Conditions
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Heart Failure, Mitral Regurgitation

Intervention / Treatment
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* Device: MitraClip


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 90 years Significant secondary mitral regurgitation (effective regurgitant orifice area ≥ 30mm2) confirmed at the end of the screening period Optimal medical therapy (OMT) according to recent guidelines. Advanced heart failure defined as the presence of all the following criteria, despite OMT: Severe and persistent symptoms of HF (NYHA class III or IV) Severe cardiac dysfunction defined by a reduced LVEF ≤35% and/or high BNP or NTproBNP levels (BNP>125 pg/ml or NTproBNP>400 pg/ml if sinus rhythm; BNP>375 pg/ml or NTproBNP>1200 pg/ml if atrial fibrillation) At least 1 unplanned visit or hospitalization in the last 12 months, due to HF, and requiring intravenous diuretics and/or inotropes Severe impairment of quality of life (KCCQ < 75 points) Severe impairment of exercise capacity with inability to exercise or low 6MWT distance (<300 meters) or pVO2 (<12-14 mL/kg/min or <50% of predicted) Exclusion Criteria: Unfavorable mitral valve anatomy, which implanting investigator judges as not successfully treatable by the MitraClip Echocardiographic evidence of intracardiac mass, thrombus or vegetation Active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic disease (i.e., noncompliant, perforated) Active infections requiring current antibiotic therapy Transesophageal echocardiography (TEE) contraindicated or at high risk Untreated significant coronary artery disease requiring revascularization Iron deficiency defined as serum ferritin <100 μg/L, or ferritin between 100-299 μg/L and transferrin saturation <20% and/or intravenous ferric carboxymaltose administration during the 30 days before randomization Coronary artery bypass graft, percutaneous coronary intervention, transcatheter aortic valve replacement or cardiac resynchronization therapy within the prior 30 days Myocardial infarction or cerebrovascular accident within prior 30 days Hemodynamic instability defined as systolic blood pressure < 90mmHg and cardiogenic shock or need for inotropic support or intra-aortic balloon pump or other hemodynamic support device. Chronic obstructive pulmonary disease, malignancy, or other comorbidities as the main cause of severe symptoms and impaired quality of life. Life expectancy <12 months due to non-cardiac conditions

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MitraClip + Optimal medical therapy<br>Patients randomized to this arm will receive percutaneous treatment of secondary mitral regurgitation by MitraClip system and Optimal medical therapy (OMT) for heart failure | Device: MitraClip<br>* MitraClip<br>|
| No Intervention: Optimal medical therapy<br>Patients randomized to this arm will receive only Optimal medical therapy (OMT) for heart failure | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change in overall KCCQ summary score (KCCQ-OS) | Kansas City Cardiomyopathy Questionnaire (KCCQ) aims at evaluating quality of life in heart failure patients using a scale including 100 points (from 0 [worst] to 100 [best]) | from baseline to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of all-cause death or unplanned HF hospitalization or change in KCCQ-OS | Unplanned HF hospitalization is defined as Admission to an inpatient unit or ward in the hospital for ≥24 h, including an emergency department stay with symptoms, signs and/or laboratory evidence of worsening heart failure; pulmonary edema, administration of intravenous therapies (loop diuretic agents, vasodilators, inotropic agents, vasopressors) or mechanical heart failure therapies (ultrafiltration, cardiac resynchronization, IABP, LVAD); hospitalizations requiring oxygen therapy. Kansas City Cardiomyopathy Questionnaire (KCCQ) aims at evaluating quality of life in heart failure patients using a scale including 100 points (from 0 [worst] to 100 [best]). | from baseline to 3, 6 and 12 months | 
| All-cause death |  | at 3 months, 6 and 12 months | 
| Cardiovascular death | Defined according to MVARC-2 definition as death due to Heart Failure, Myocardial Infarction, Major/Disabling Bleeding, Tromboembolism, Stroke, Arrythmia, Cardiovascular Infection, Cardiac Tamponade, Sudden Death, Device Failure | at 3 months, 6 and 12 months | 
| Unplanned HF hospitalization | Admission to an inpatient unit or ward in the hospital for ≥24 h, including an emergency department stay with symptoms, signs and/or laboratory evidence of worsening heart failure; pulmonary edema, administration of intravenous therapies (loop diuretic agents, vasodilators, inotropic agents, vasopressors) or mechanical heart failure therapies (ultrafiltration, cardiac resynchronization, IABP, LVAD); hospitalizations requiring oxygen therapy. | at 3, 6 and 12 months | 
| Absolute change in KCCQ-OS | Kansas City Cardiomyopathy Questionnaire aims at evaluating quality of life in heart failure patients using a scale including 100 points (from 0 [worst] to 100 [best]) | from baseline to 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Mitral Regurgitation, MitraClip, Optimal medical therapy