Early Mitral ValvE Repair Versus Watchful Waiting for Asymptomatic SEvere Degenerative Mitral Regurgitation (REVERSE-MR)

Randomized Comparison of Early Mitral ValvE Repair Versus Watchful Waiting for Asymptomatic SEvere Degenerative Mitral Regurgitation Due to Leaflet Prolapse

Degenerative mitral regurgitation (MR) due to leaflet prolapse is frequent and can be surgically repaired in the vast majority of patients. Despite the efficacy of mitral valve repair, an ongoing international controversy exists regarding the need to perform early surgery in asymptomatic patients with severe MR and no sign of LV dysfunction in whom the probability of successful and durable repair is very high. In this group of patients, differing views of the risks of uncorrected severe MR exist: considered as benign by those supporting medical "watchful waiting" or associated with significant excess mortality/morbidity by those advocating early surgery. This controversy can only be resolved by a randomized controlled trial which is still lacking.

The main objective is to demonstrate the superiority of early mitral valve repair in patients with asymptomatic severe MR due to leaflet prolapse compared to an initial conservative management in terms of all-cause death and cardiovascular morbidity during five years follow-up.

Study Overview

• Status: Recruiting
• Conditions: Degenerative Mitral Regurgitation (MR) Due to Leaflet Prolapse
• Intervention / Treatment: Procedure: Surgery; Other: Clinical interview and echocardiography

Detailed Description

Experimental group: In patients randomized to early mitral valve repair, surgery will be performed within 3 months after randomization. Clinical interview will be performed at discharge, at 6 months and afterwards yearly until the end of follow-up. Echocardiography will be performed at discharge, at 6 months and at the end of follow-up.

Control group: Patients randomized to initial conservative management will be followed up by clinical interview and echocardiography every 6 months. Patients will be instructed to report any change in functional status in a prompt manner. Surgery will be indicated at the onset of symptoms or if one or more of the following occur during follow-up: LV end-systolic diameter >40mm, LV ejection fraction <60%, recurrent atrial fibrillation, or resting systolic pulmonary artery pressure >50mmHg.

• Study Type: Interventional
• Enrollment (Anticipated): 424
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christophe TRIBOUILLOY, MD, phD; Phone Number: 0033 322 087 250; Email: tribouilloy.christophe@chu-amiens.fr

Study Locations

• France
  • Amiens, France, 80054
    • Recruiting
    • CHU Amiens-Picardie
  • Saint-Denis, France, 93200
    • Recruiting
    • Centre Cardiologique du Nord
    • Contact: Thomas GOISSEN; Phone Number: 0033 01 49 33 41 38; Email: thomas.goissen@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Asymptomatic patients according history or an exercise test in those able to perform it if there is a doubt about the absence of symptoms
• Severe (grade IV) degenerative MR due to leaflet prolapse assessed by echocardiography
• LV ejection fraction by Simpson biplane method ≥60% and LV end-systolic diameter by TM echocardiography ≤40mm
• Sinus rhythm on the inclusion ECG
• Pulmonary artery pressure ≤50 mmHg by Doppler echocardiography.
• High probability of mitral valve repair
• EuroSCORE II ≤ 3%

Exclusion Criteria:

• Mitral stenosis or > mild aortic valve disease (stenosis or regurgitation)
• Congenital heart disease (except patent foramen ovale or atrial septal defect)
• Patients with cardiac prostheses
• Previous myocardial infarction
• Previous cardiac surgery
• Extra cardiac comorbidity with life expectancy < 5 years
• Recent history of psychiatric disease (including drug or alcohol abuse)
• Therapy with an investigational intervention at the time of screening or plan to enrol patient in additional intervention study during participation in this trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early mitral valve repair; Surgery will be performed within 3 months after randomization. Clinical interview will be performed at discharge, at 6 months and afterwards yearly until the end of follow-up. Echocardiography will be performed at discharge, at 6 months and at the end of follow-up.	Procedure: Surgery; Early mitral valve repair
Active Comparator: Conservative management; Patients will be followed up by clinical interview and echocardiography every 6 months.	Other: Clinical interview and echocardiography; Clinical interview and echocardiography every 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
death and occurrence of adverse cardiovascular events	Time from randomization to the first occurrence of one of the following composite end-point including all-cause death and occurrence of adverse cardiovascular events (heart failure, atrial fibrillation, infective endocarditis, cerebrovascular events).	during 5 years

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire, Amiens

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2018
• Primary Completion (Anticipated): January 1, 2025
• Study Completion (Anticipated): January 1, 2026

Study Registration Dates

• First Submitted: December 26, 2017
• First Submitted That Met QC Criteria: January 2, 2018
• First Posted (Actual): January 3, 2018

Study Record Updates

• Last Update Posted (Actual): June 8, 2018
• Last Update Submitted That Met QC Criteria: June 6, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Heart Valve Diseases; Mitral Valve Insufficiency; Prolapse
• Other Study ID Numbers: PI2017_843_0005; 2017-A00364-49 (Registry Identifier: ID-RCB number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No