Clinical trial NCT05292716: Mitral Regurgitation Treatment in Advanced Heart Failure
Official title: Mitral Regurgitation Treatment in Advanced Heart Failure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure
Mitral Regurgitation
Keywords: Heart Failure
Mitral Regurgitation
MitraClip
Optimal medical therapy
Lead sponsor: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Sponsor class: OTHER
First posted: 2022-03-23
Enrollment: 172
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* Age between 18 and 90 years
* Significant secondary mitral regurgitation (effective regurgitant orifice area ≥ 5 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 left ventricular ejection fraction (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)
  * Impairment of quality of life (KCCQ \< 75 points) AND severe impairment of exercise capacity with inability to exercise or low 6MWT distance (\<450 meters) or pVO2 (\<14 mL/kg/min or \<50% of predicted) OR at least 1 unplanned visit or hospitalization in the last 12 months, due to HF, and requiring intravenous diuretics and/or inotropes.

Exclusion Criteria:

* Unfavorable mitral valve anatomy, which implanting investigator judges as not successfully treatable by the MitraClip (i.e. mitral valve area \<3 mm2, leaflet length \<7 mm)
* 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
* Pulmonary vein ablation or cardioversion leading to restore of sinus rhythm or AV node ablation in the last 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

Primary outcomes:
measure: Absolute change in overall KCCQ summary score (KCCQ-OS)
timeFrame: from baseline to 3 months
Secondary outcomes:
measure: Composite of all-cause death or unplanned HF hospitalization or change in KCCQ-OS
timeFrame: from baseline to 3, 6 and 12 months
measure: All-cause death
timeFrame: at 3 months, 6 and 12 months
measure: Cardiovascular death
timeFrame: at 3 months, 6 and 12 months
measure: Unplanned HF hospitalization
timeFrame: at 3, 6 and 12 months
measure: Absolute change in KCCQ-OS
timeFrame: from baseline to 6 and 12 months
measure: Recurrent HF events
timeFrame: at 3, 6 and 12 months
Other outcomes:
measure: Absolute change in EQ-5D
timeFrame: from baseline to 3, 6 and 12 months
measure: Patients' Global Impression of Change (PGIC) Scale
timeFrame: at 3, 6 and 12 months
measure: Change in NYHA class
timeFrame: from baseline to 3, 6 and 12 months
measure: Absolute and percentage change in 6-minute walk test (6MWT) distance in meters
timeFrame: from baseline to 3, 6 and 12 months
measure: Absolute change and percentage in NT-proBNP levels in pg/mL
timeFrame: from baseline to 3, 6 and 12 months.
measure: Absolute and percentage change in systolic pulmonary pressure (mmHg) assessed by echocardiography
timeFrame: from baseline to 3, 6 and 12 months
measure: Absolute and percentage change in left atrial volume (mL)
timeFrame: from baseline to 3, 6 and 12 months.
measure: Absolute and percentage change in left ventricular end-diastolic and end-systolic volumes (mL)
timeFrame: from baseline to 3, 6 and 12 months
measure: Absolute and percentage change in right ventricular fractional area change (FAC) (percent)
timeFrame: from baseline to 3, 6 and 12 months
measure: Absolute and percentage change in diuretic dose
timeFrame: from baseline to 3, 6 and 12 months
Locations:
city: Brescia
country: Italy
facility: Marianna Adamo
state: Lombardy
Study officials:
References: