Functional Mitral RegurgitationEVOLVE-HFNCT02985268
Evaluation of Outcomes of CRT and MitraClip for Treatment of Low Ejection Fraction and Functional Mitral Regurgitation in HF
A study testing MitraClip, Optimal Medical Therapy and CRT-D in people with Functional Mitral Regurgitation and Heart Failure, run by Montreal Heart Institute.
Trial summary
At present, the optimal treatment strategy for heart failure patients and moderate-to-severe (3+) or severe (4+) mitral regurgitation with a class IIa recommendation for CRT is uncertain.Whether these patents should also be treated for functional mitral regurgitation or with CRT also remains unclear. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Functional Mitral Regurgitation, Heart Failure
- What is being tested?
- MitraClip, Optimal Medical Therapy and CRT-D
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Dec 2016to Feb 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Symptomatic moderate-to-severe (3+) or severe (4+) functional mitral regurgitation due to cardiomyopathy of either ischemic or non-ischemic etiology as determined by transthoracic echocardiogram (TTE), and confirmed by the Echocardiography Core Lab (ECL);
- Symptomatic heart failure as defined by New York Heart Association (NYHA) class II, III or ambulatory IV;
- Treatment and compliance with optimal medical therapy for heart failure for at least 30 days; Optimal medical therapy is defined by: Maximum tolerated beta-blocker, angiotensin converting enzyme inhibitor (ACE) or angiotensin receptor blocker (ARB), and aldosterone antagonist (as per the ACCF/AHA Guidelines as judged by the HF specialist investigator on site and confirmed by the Clinical Eligibility Committee).
- Left ventricular ejection fraction ≤ 35%, as assessed by any one of the following methods: echocardiography, contrast left ventriculography, gated blood pool scan or cardiac magnetic resonance imaging (MRI);
- Class IIa indication for cardiac resynchronization therapy:
- Left bundle branch block (LBBB) and QRS duration of 120-149 ms;
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- Right bundle branch block (RBBB) and QRS ≥ 150 ms.
- Clinical agreement amongst local investigators that the patient will not be offered surgical intervention;
- The primary regurgitant jet, in the opinion of the MitraClip implanting investigator, can successfully be treated by the MitraClip. Treatment of commissural mitral regurgitation may be treated at the discretion of the operator. All major jets contributing the secondary MR will be treated with the MitraClip;
- Ability to perform a six-minute walk test (6MWT) without substantial physical limitations and without use of a walker or wheelchair and distance walked in 6 minutes of ≤ 450m;
- Ability and willingness to give written informed consent and to comply with the requirements of the study.
Who cannot join
- Life expectancy less than 12 months due to noncardiac conditions;
- ACC/AHA Stage D Heart Failure;
- Left ventricular ejection fraction ≤ 15%;
- Hypotension (systolic pressure <90 mm Hg) or requirement for inotropic support or mechanical hemodynamic support;
- United Network for Organ Sharing (UNOS) status 1 heart transplantation or prior orthotopic heart transplantation;
- Untreated clinically significant coronary artery disease requiring revascularization;
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- CABG within prior 30 days;
- Percutaneous coronary intervention within prior 30 days;
- Severe Chronic Obstructive Pulmonary Disease (COPD) requiring continuous daytime home oxygen or chronic oral corticosteroid therapy;
- Previous surgical mitral valve bioprosthesis, mitral annuloplasty, or transcatheter mitral valve procedure;
- Positive pregnancy test, or woman of child bearing potential not using highly effective methods of contraception;
- Mitral valve area <4.0 cm2 as assessed by planimetry of the mitral valve;
- Subjects in whom trans-esophageal echocardiography is contraindicated or high risk;
- Mitral leaflet anatomy which may preclude MitraClip implantation:
- Perforated mitral leaflets or clefts, lack of primary or secondary chordal support;
- Severe calcification in the grasping area;
- Rheumatic valve disease.
- Previously implanted Cardiac Resynchronization Therapy and Defibrillator (CRT-D) system;
- Stroke or transient ischemic event within 30 days before randomization;
- Modified Rankin Scale >4 disability;
- Need for emergent or urgent surgery for any reason or any planned cardiac surgery within the next 12 months;
- Severe renal impairment defined as an Estimated Glomerular Filtration Rate (eGFR) <30 mL/min/1.73m2 as calculated by the Modification in Diet in Renal Disease (MDRD) formula;
- Severe anemia requiring transfusional support or therapy with erythropoietin;
- Physical evidence of right-sided congestive heart failure with echocardiographic evidence of moderate or severe right ventricular dysfunction;
- Aortic valve disease requiring surgery or transcatheter intervention;
- Significant tricuspid valve disease requiring surgical intervention or very severe tricuspid regurgitation;
- Active infection requiring antibiotic therapy;
- Active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic disease;
- Echocardiographic evidence of intracardiac mass, thrombus or vegetation;
- Any condition making it unlikely the patient will be able to complete all protocol procedures (including compliance with guideline directed medical therapy) and follow-up visits;
- Presence of any of the following:
- Pulmonary artery systolic pressure (PASP) > 70 mm Hg confirmed by right heart catheterization;
- Infiltrative cardiomyopathies.
- Any other condition(s) that would compromise the safety of the patient as judged by the site principal investigator.
About this study
Official title: Evaluation of Outcomes of Cardiac Resynchronization Therapy and MitraClip for the Treatment of Low Ejection Fraction and Functional Mitral Valve Regurgitation in Heart Failure
At present, the optimal treatment strategy for heart failure patients and moderate-to-severe (3+) or severe (4+) mitral regurgitation with a class IIa recommendation for CRT is uncertain.Whether these patents should also be treated for functional mitral regurgitation or with CRT also remains unclear. We therefore propose a randomized 2x2 factorial design in this patient population to understand the the impact of both CRT and transcatheter mitral valve repair with the MitraClip on their functional status and quality of life.
- Conditions
- Functional Mitral Regurgitation, Heart Failure
- Being tested
- MitraClip, Optimal Medical Therapy, CRT-D
- Keywords
- MitraClip, Cardiovascular resynchronization therapy, Six minute walk test, Mitral regurgitation, CRT-D
- Medical subject headings
- Heart Failure, Mitral Valve Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MitraClipDevice
The MitraClip Clip Delivery System is indicated for the percutaneous reduction of significant symptomatic mitral regurgitation (MR ≥ 3+) due to primary abnormality of the mitral apparatus [degenerative MR] in patients who have been determined to be at prohibitive risk for mitral valve surgery by a heart team, which includes a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced in mitral valve disease, and in whom existing comorbidities would not preclude the expected benefit from reduction of the mitral regurgitation.
Optimal Medical TherapyDrug
Also called OMT
Optimal medical therapy administered as per the Guideline Direct Medical Therapy (GDMT) as defined in the 2013 ACCF/AHA Heart Failure Guidelines with maximum tolerated doses of an ACE-inhibitor or Angiotensin Receptor Blocker (ARB) and beta-blocker
CRT-DDevice
Also called Cardiac Resynchronization Therapy and Defibrillator
Cardiac Resynchronization Therapy with defibrillation therapy devices will be implanted according to the Heart Rhythm Society Guidelines for implanted devices.
| Study group | Role | What they receive |
|---|---|---|
| MitraClip/Optimal Medical Therapy (OMT) and CRT ON | Active comparator | Patient to be implanted with both MitraClip and CRT-D. Will also receive optimal medical therapy. CRT-D will be programmed to ON Receives: Device: MitraClip; Drug: Optimal Medical Therapy; Device: CRT-D |
| MitraClip/OMT and CRT OFF | Active comparator | Patient to be implanted with both MitraClip and CRT-D. Will also receive optimal medical therapy. CRT-D will be programmed to OFF until the 6-month follow-up visit in which the CRT will be turned ON Receives: Device: MitraClip; Drug: Optimal Medical Therapy; Device: CRT-D |
| OMT and CRT ON | Active comparator | Patient to be implanted with only the CRT-D and will receive optimal medical therapy.
CRT-D will be programmed to ON Receives: Drug: Optimal Medical Therapy; Device: CRT-D |
| OMT and CRT OFF | Active comparator | Patient to be implanted with only the CRT-D and will receive optimal medical therapy.
CRT-D will be programmed to OFF until the 6-month follow-up visit in which the CRT will be turned ON Receives: Drug: Optimal Medical Therapy; Device: CRT-D |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in distance walked on a six-minute walk test (6MWT)
Measured: Baseline to 6 months
Secondary outcomes (6)
Change in cardiographic endpoints
Mitral regurgitation severity
Measured: Baseline to 6 months
Change in cardiographic endpoints
Indexed left ventricular end-systolic volume (LVESVi)
Measured: Baseline to 6 months
Change in cardiographic endpoints
Left ventricular ejection fraction (LVEF)
Measured: Baseline to 6 months
Change in Quality of Life Assessment scores
Kansas City Cardiomyopathy Questionnaire (KCCQ)
Measured: Baseline to 6 months
Change in Quality of Life Assessment scores
Euro Quality of Life Questionnaire (EQ5DL)
Measured: Baseline to 6 months
Number of Re-hospitalizations for decompensated heart failure
Measured: 6 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2016 (estimated)
- Study startDec 2016
- Primary completionDec 2019 (estimated)
- Study completionFeb 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Functional Mitral RegurgitationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Montreal Heart Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anita Asgar, MD, Principal investigator, Montreal Heart Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02985268
- Sponsor's protocol ID
- MHICC-2016-001
- Acronym
- EVOLVE-HF
- Status last verified
- Feb 2020
- First submitted
- 1 Dec 2016
- Last updated
- 27 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Outcomes of Cardiac Resynchronization Therapy and MitraClip for the Treatment of Low Ejection Fraction and Functional Mitral Valve Regurgitation in Heart Failure
- ClinicalTrials.gov ID
- NCT02985268
- Acronym / sponsor ID
- EVOLVE-HF / MHICC-2016-001
- Conditions
- Functional Mitral Regurgitation, Heart Failure
- Keywords
- MitraClip, Cardiovascular resynchronization therapy, Six minute walk test, Mitral regurgitation, CRT-D
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Montreal Heart InstituteUniversity, hospital or other
- Study start
- Dec 2016
- Primary completion
- Dec 2019 (estimated)
- Study completion
- Feb 2020 (estimated)
- First posted
- 7 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
At present, the optimal treatment strategy for heart failure patients and moderate-to-severe (3+) or severe (4+) mitral regurgitation with a class IIa recommendation for CRT is uncertain.Whether these patents should also be treated for functional mitral regurgitation or with CRT also remains unclear. We therefore propose a randomized 2x2 factorial design in this patient population to understand the the impact of both CRT and transcatheter mitral valve repair with the MitraClip on their functional status and quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| MitraClip/Optimal Medical Therapy (OMT) and CRT ON | Active comparator | Device: MitraClip, Drug: Optimal Medical Therapy, Device: CRT-DPatient to be implanted with both MitraClip and CRT-D. Will also receive optimal medical therapy. CRT-D will be programmed to ON |
| MitraClip/OMT and CRT OFF | Active comparator | Device: MitraClip, Drug: Optimal Medical Therapy, Device: CRT-DPatient to be implanted with both MitraClip and CRT-D. Will also receive optimal medical therapy. CRT-D will be programmed to OFF until the 6-month follow-up visit in which the CRT will be turned ON |
| OMT and CRT ON | Active comparator | Drug: Optimal Medical Therapy, Device: CRT-DPatient to be implanted with only the CRT-D and will receive optimal medical therapy. CRT-D will be programmed to ON |
| OMT and CRT OFF | Active comparator | Drug: Optimal Medical Therapy, Device: CRT-DPatient to be implanted with only the CRT-D and will receive optimal medical therapy. CRT-D will be programmed to OFF until the 6-month follow-up visit in which the CRT will be turned ON |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Symptomatic moderate-to-severe (3+) or severe (4+) functional mitral regurgitation due to cardiomyopathy of either ischemic or non-ischemic etiology as determined by transthoracic echocardiogram (TTE), and confirmed by the Echocardiography Core Lab (ECL);
- Symptomatic heart failure as defined by New York Heart Association (NYHA) class II, III or ambulatory IV;
- Treatment and compliance with optimal medical therapy for heart failure for at least 30 days; Optimal medical therapy is defined by: Maximum tolerated beta-blocker, angiotensin converting enzyme inhibitor (ACE) or angiotensin receptor blocker (ARB), and aldosterone antagonist (as per the ACCF/AHA Guidelines as judged by the HF specialist investigator on site and confirmed by the Clinical Eligibility Committee).
- Left ventricular ejection fraction ≤ 35%, as assessed by any one of the following methods: echocardiography, contrast left ventriculography, gated blood pool scan or cardiac magnetic resonance imaging (MRI);
- Class IIa indication for cardiac resynchronization therapy:
Key exclusion criteria (34 listed)
- Life expectancy less than 12 months due to noncardiac conditions;
- ACC/AHA Stage D Heart Failure;
- Left ventricular ejection fraction ≤ 15%;
- Hypotension (systolic pressure <90 mm Hg) or requirement for inotropic support or mechanical hemodynamic support;
- United Network for Organ Sharing (UNOS) status 1 heart transplantation or prior orthotopic heart transplantation;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MitraClipThe MitraClip Clip Delivery System is indicated for the percutaneous reduction of significant symptomatic mitral regurgitation (MR ≥ 3+) due to primary abnormality of the mitral apparatus [degenerative MR] in patients who have been determined to be at prohibitive risk for mitral valve surgery by a heart team, which includes a cardiac surgeon experienced in mitral valve surgery and a cardiologist experienced in mitral valve disease, and in whom existing comorbidities would not preclude the expected benefit from reduction of the mitral regurgitation. | Device | MitraClip/OMT and CRT OFF, MitraClip/Optimal Medical Therapy (OMT) and CRT ON |
| Optimal Medical TherapyAlso: OMTOptimal medical therapy administered as per the Guideline Direct Medical Therapy (GDMT) as defined in the 2013 ACCF/AHA Heart Failure Guidelines with maximum tolerated doses of an ACE-inhibitor or Angiotensin Receptor Blocker (ARB) and beta-blocker | Drug | MitraClip/OMT and CRT OFF, MitraClip/Optimal Medical Therapy (OMT) and CRT ON, OMT and CRT OFF, OMT and CRT ON |
| CRT-DAlso: Cardiac Resynchronization Therapy and DefibrillatorCardiac Resynchronization Therapy with defibrillation therapy devices will be implanted according to the Heart Rhythm Society Guidelines for implanted devices. | Device | MitraClip/OMT and CRT OFF, MitraClip/Optimal Medical Therapy (OMT) and CRT ON, OMT and CRT OFF, OMT and CRT ON |
Primary outcome
Improvement in distance walked on a six-minute walk test (6MWT)
Time frame: Baseline to 6 months
6 secondary outcomes
Change in cardiographic endpoints
Time frame: Baseline to 6 months
Change in cardiographic endpoints
Time frame: Baseline to 6 months
Change in cardiographic endpoints
Time frame: Baseline to 6 months
Change in Quality of Life Assessment scores
Time frame: Baseline to 6 months
Change in Quality of Life Assessment scores
Time frame: Baseline to 6 months
Number of Re-hospitalizations for decompensated heart failure
Time frame: 6 and 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2020.
- Individual participant dataSharing planned: No
Related trials for Functional Mitral Regurgitation
Not yet recruitingObservational study
Multi-center Study of Three-Dimensional Transesophageal Echocardiography in Patients With Secondary Mitral Regurgitation
Mitral Valve Insufficiency
Recruiting
Mitral Valve Edge-to-Edge Repair in Patients With Exercise-Induced Severe Mitral Regurgitation
Heart Failure - NYHA II - IV, Mitral Regurgitation Functional
Recruiting
Achieving Optimal Medical Therapy Through Percutaneous Treatment of Secondary Mitral Regurgitation to Improve Outcome in Patients With HFrEF
Mitral Regurgitation Functional, Heart Failure With Reduced Ejection Fraction (HFrEF)
Recruiting
PRECISE-AFMR I: Transcatheter Mitral Valve Edge-to-Edge Repair for Atrial Functional Mitral Regurgitation in Patients at High Surgical Risk
Atrial Functional, Mitral Regurgitation (MR)
Active, not recruiting
A Feasibility Study of the Millipede Transcatheter Annuloplasty Ring System in Patients With Functional Mitral Regurgitation
Mitral Regurgitation Functional, Mitral Valve Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anita Asgar, MD principal investigator
Montreal Heart Institute
Questions about this trial
What is this clinical trial studying?
A study testing MitraClip, Optimal Medical Therapy and CRT-D in people with Functional Mitral Regurgitation and Heart Failure, run by Montreal Heart Institute.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 27 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in distance walked on a six-minute walk test (6MWT) (time frame: Baseline to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2020.