Back to results

Mitral Regurgitation Treatment in Advanced Heart Failure (MITRADVANCE)

Primary Purpose

Heart Failure, Mitral Regurgitation

Status

Recruiting

Phase

Not Applicable

Locations

Italy

Study Type

Interventional

Intervention

MitraClip

About this trial

This is an interventional other trial for Heart Failure focused on measuring Heart Failure, Mitral Regurgitation, MitraClip, Optimal medical therapy

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Marianna AdamoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

MitraClip + Optimal medical therapy

Optimal medical therapy

Arm Description

Patients randomized to this arm will receive percutaneous treatment of secondary mitral regurgitation by MitraClip system and Optimal medical therapy (OMT) for heart failure

Patients randomized to this arm will receive only Optimal medical therapy (OMT) for heart failure

Outcomes

Primary Outcome Measures

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])

Secondary Outcome Measures

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]).

All-cause death

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

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.

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])

Full Information

NCT ID

NCT05292716

First Posted

February 20, 2022

Last Updated

July 24, 2022

Sponsor

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

1. Study Identification

Unique Protocol Identification Number

NCT05292716

Brief Title

Mitral Regurgitation Treatment in Advanced Heart Failure

Acronym

MITRADVANCE

Official Title

Mitral Regurgitation Treatment in Advanced Heart Failure

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Recruiting

Study Start Date

April 21, 2021 (Actual)

Primary Completion Date

April 21, 2024 (Anticipated)

Study Completion Date

April 21, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Heart Failure, Mitral Regurgitation

Keywords

Heart Failure, Mitral Regurgitation, MitraClip, Optimal medical therapy

7. Study Design

Primary Purpose

Other

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

172 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

MitraClip + Optimal medical therapy

Arm Type

Experimental

Arm Description

Patients randomized to this arm will receive percutaneous treatment of secondary mitral regurgitation by MitraClip system and Optimal medical therapy (OMT) for heart failure

Arm Title

Optimal medical therapy

Arm Type

No Intervention

Arm Description

Patients randomized to this arm will receive only Optimal medical therapy (OMT) for heart failure

Intervention Type

Device

Intervention Name(s)

MitraClip

Intervention Description

MitraClip

Primary Outcome Measure Information:

Title

Absolute change in overall KCCQ summary score (KCCQ-OS)

Description

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])

Time Frame

from baseline to 3 months

Secondary Outcome Measure Information:

Title

Composite of all-cause death or unplanned HF hospitalization or change in KCCQ-OS

Description

Time Frame

from baseline to 3, 6 and 12 months

Title

All-cause death

Time Frame

at 3 months, 6 and 12 months

Title

Cardiovascular death

Description

Time Frame

at 3 months, 6 and 12 months

Title

Unplanned HF hospitalization

Description

Time Frame

at 3, 6 and 12 months

Title

Absolute change in KCCQ-OS

Description

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])

Time Frame

from baseline to 6 and 12 months

Other Pre-specified Outcome Measures:

Title

Absolute change in EQ-5D

Description

The EQ-5D questionnaire is standardized instrument for measuring generic health status using five dimensions. Each dimension has 5 levels. The final number is icluded between 0 and 1 (0=worst and 1=best)

Time Frame

from baseline to 3, 6 and 12 months

Title

Patients' Global Impression of Change (PGIC) Scale

Description

The Patients' Global Impression of Change (PGIC) Scale will assess the degree of change in patient's health status in terms of overall improvement (very much improved, much improved, minimally improved, unchanged, minimally worse, much worse, very much worse.

Time Frame

at 3, 6 and 12 months

Title

Change in NYHA class

Description

The New York Heart Association scale include 4 level of heart failure symptoms: 1=No limitation of physical activity, ordinary physical activity does not cause undue fatigue or dyspnea; 2= Slight limitation of physical activity, ordinary physical activity results in fatigue or dyspnea; 3: Marked limitation of physical activity, less than ordinary activity causes fatigue or dyspnea; 4=Symptoms of heart failure at rest

Time Frame

from baseline to 3, 6 and 12 months

Title

Absolute and percentage change in 6-minute walk test (6MWT) distance in meters

Time Frame

from baseline to 3, 6 and 12 months

Title

Absolute change and percentage in NT-proBNP levels in pg/mL

Time Frame

from baseline to 3, 6 and 12 months.

Title

Absolute and percentage change in systolic pulmonary pressure (mmHg) assessed by echocardiography

Time Frame

from baseline to 3, 6 and 12 months

Title

Absolute and percentage change in left atrial volume (mL)

Time Frame

from baseline to 3, 6 and 12 months.

Title

Absolute and percentage change in left ventricular end-diastolic and end-systolic volumes (mL)

Time Frame

from baseline to 3, 6 and 12 months

Title

Absolute and percentage change in right ventricular fractional area change (FAC) (percent)

Time Frame

from baseline to 3, 6 and 12 months

Title

Absolute and percentage change in diuretic dose

Time Frame

from baseline to 3, 6 and 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Facility Information:

Facility Name

Marianna Adamo

City

Brescia

State/Province

Lombardy

ZIP/Postal Code

25123

Country

Italy

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marianna Adamo, MD

Phone

+393897834503

mariannaadamo@hotmail.com

12. IPD Sharing Statement

Learn more about this trial

Mitral Regurgitation Treatment in Advanced Heart Failure

We'll reach out to this number within 24 hrs