The Dutch Asymptomatic Mitral Regurgitation Trial

Not Applicable

Terminated

• Conditions: Heart; Disease, Mitral(Valve); Mitral Valve Insufficiency; Diseases of Mitral Valve
• Interventions: Other: Watchful waiting; Procedure: Early mitral valve repair

• Registration Number: NCT01708265
• Lead Sponsor: UMC Utrecht

Brief Summary

The purpose of this study is to compare early mitral valve repair versus a watchful waiting strategy in asymptomatic patients with severe organic mitral valve regurgitation and preserved left ventricular function.

Detailed Description

Severe asymptomatic organic mitral valve (MV) regurgitation with preserved left ventricular (LV) function is a challenging clinical entity as data on the recommended treatment strategy for these patients are scarce and conflicting, which is reflected in current guidelines. European guidelines advocate a more conservative strategy i.e. watchful waiting, with yearly echocardiography, whilst American guidelines are more in favour of early surgery to reconstruct the MV, i.e. MV repair (in contrast to MV replacement) in order to prevent future LV dysfunction and complaints.

A number of non-randomised trials show a favourable outcome of early surgery and the early surgery strategy has shown to be associated with improved long-term survival, decreased cardiac mortality and decreased morbidity compared with the conservative management \[citations 1-3\]. On the other hand, non-randomised trials describe also that a conservative strategy (i.e. watchful waiting) can be safely accomplished. If facilitated surgery is performed in this population it has proven to be eventually associated with good perioperative and postoperative outcome in 50% of the patients at 10 years when careful follow-up is being carried out \[citation 4\]. Non-randomised trials inherently have a number of drawbacks. A randomised trial comparing both strategies and objectivising the best treatment strategy has never been performed.

The Dutch AMR (Asymptomatic Mitral Regurgitation) trial is a multicenter, prospective, randomised trial comparing early MV repair versus watchful waiting in asymptomatic patients with severe organic MV regurgitation and preserved LV function \[citation 5, 6\].

Study Timeline

• Study First Submitted: 2012-10-11
• Study First Submitted QC: 2012-10-15
• Study First Posted: 2012-10-16
• Study Start: 2013-02
• Status Verified: 2016-11
• Last Update Submitted: 2016-11-22
• Last Update Posted: 2016-11-23
• Primary Completion: 2021-02
• Study Completion: 2021-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Asymptomatic
• Severe organic mitral valve regurgitation.
• Preserved left ventricular function (left ventricular ejection fraction >60% and left ventricular end-systolic dimension ≤45 mm)
• The likelihood of MV repair should be more than 90% determined by the local heart team with a cardiologist and cardiothoracic surgeon

Exclusion Criteria

• Pulmonary hypertension (>50 mmHg at rest)
• Atrial fibrillation
• Physical inability as determined by the heart team to undergo surgery
• Other life-threatening morbidity
• Higher expected surgical risks in advance, according to the dedicated heart team
• Moderate to severe kidney disease (eGFR less than 30 mL/min)
• Flail leaflet together with a left ventricular end systolic diameter (LVESD) >40 mm

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Watchful waiting	Watchful waiting	Watchful waiting
Early mitral valve repair	Early mitral valve repair	Early mitral valve repair

Primary Outcome Measures

Name	Time	Method
Composite endpoint: cardiovascular mortality, congestive heart failure and hospitalization for nonfatal cardiovascular events	Min. 5 years	The primary outcome is defined as 'time to first event'. It concerns time to first event of the composite endpoint of cardiovascular mortality, congestive heart failure, non-fatal cardiovascular events requiring hospitalization, defined as: stroke/cerebrovascular accident (CVA), atrial fibrillation (permanent or requiring hospitalization) and/or reoperation after elective MV surgery.

Secondary Outcome Measures

Name	Time	Method
Cardiovascular mortality	Min. 5 years	Secondary outcome measures are the separate components of the composite primary endpoint: cardiovascular mortality, congestive heart failure, hospitalization for nonfatal cardiovascular events (stroke/cerebrovascular accident (CVA), AF (permanent or requiring hospitalization) and reoperation after elective MV surgery).
Congestive heart failure	Min. 5 years	Secondary outcome measures are the separate components of the composite primary endpoint: cardiovascular mortality, congestive heart failure, hospitalization for nonfatal cardiovascular events (stroke/cerebrovascular accident (CVA), AF (permanent or requiring hospitalization) and reoperation after elective MV surgery).
Hospitalization for nonfatal cardiovascular events	Min. 5 years	Secondary outcome measures are the separate components of the composite primary endpoint: cardiovascular mortality, congestive heart failure, hospitalization for nonfatal cardiovascular events (stroke/cerebrovascular accident (CVA), AF (permanent or requiring hospitalization) and reoperation after elective MV surgery).
All-cause mortality	Min. 5 years	Secondary outcome measures the incidence of all-cause mortality at a minimum of 5 years.
Costs and effectiveness	Min. 5 years	Secondary outcome measures total direct and indirect costs and cost-effectiveness at a minimum of 5 years.
Health-related quality of life	Min. 5 years	Secondary outcome measures health-related quality of life at a minimum of 5 years.
Echocardiographic parameters	Min. 5 years	Secondary outcome measures echocardiographic parameters at a minimum of 5 years.
CMR parameters	Min. 5 years.	Secondary outcome measures Cardiovascular Magnetic Resonance imaging (CMR) parameters at a minimum of 5 years.
Paroxysmal atrial fibrillation	Min. 5 years	Secondary outcome measures the incidence of paroxysmal atrial fibrillation at a minimum of 5 years.
Exercise test parameters	Min. 5 years.	Secondary outcome measures exercise test parameters at a minimum of 5 years.
BNP	Min. 5 years	Secondary outcome measures brain natriuretic peptide (BNP) plasma levels at a minimum of 5 years.
Myocardial infarction	Min. 5 years	Secondary outcome measures the incidence of myocardial infarction at a minimum of 5 years.
Pacemaker implantation	Min. 5 years	Secondary outcome measures the incidence of pacemaker implantation at a minimum of 5 years.
Transient ischemic attack	Min. 5 years	Secondary outcome measures the incidence of transient ischemic attack (TIA) at a minimum of 5 years.
Pulmonary embolism	Min. 5 years	Secondary outcome measures the incidence of pulmonary embolism at a minimum of 5 years.

Trial Locations

Locations (4)

Leiden University Medical Center; 🇳🇱 Leiden, South Holland, Netherlands

University Medical Center Utrecht (UMC Utrecht); 🇳🇱 Utrecht, Netherlands

Amsterdam Medisch Centrum; 🇳🇱 Amsterdam, Netherlands

Amphia Hospital; 🇳🇱 Breda, Netherlands