The Dutch Asymptomatic Mitral Regurgitation Trial (Dutch AMR)

This study is currently recruiting participants.
Verified February 2013 by UMC Utrecht
Sponsor:
Collaborators:
Leiden University Medical Center
The Interuniversity Cardiology Institute of the Netherlands
WCN, Dutch Network for Cardiovascular Research
Information provided by (Responsible Party):
S.A.J. Chamuleau, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT01708265
First received: October 11, 2012
Last updated: February 5, 2013
Last verified: February 2013
  Purpose

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.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Dutch AMR; Early Mitral Valve Repair Versus Watchful Waiting in Asymptomatic Patients With Severe Organic Mitral Regurgitation; a Multicenter, Randomised Trial.

Resource links provided by NLM:


Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • Composite endpoint: cardiovascular mortality, congestive heart failure and hospitalization for nonfatal cardiovascular events [ Time Frame: Min. 5 years ] [ Designated as safety issue: Yes ]
    The primary outcome is defined as time to first event of the composite endpoint of cardiovascular mortality, congestive heart failure and hospitalization for nonfatal cardiovascular events


Secondary Outcome Measures:
  • Cardiovascular mortality [ Time Frame: Min. 5 years ] [ Designated as safety issue: Yes ]
    Secondary outcome measures the separate component cardiovascular mortality at a minimum of 5 years.

  • Congestive heart failure [ Time Frame: Min. 5 years ] [ Designated as safety issue: Yes ]
    Secondary outcome measures the separate component congestive heart failure at a minimum of 5 years.

  • Hospitalization for nonfatal cardiovascular events [ Time Frame: Min. 5 years ] [ Designated as safety issue: Yes ]
    Secondary outcome measures the separate component hospitalization for nonfatal cardiovascular events (including but not limited to acute coronary syndrome, arrhythmia and heart surgery) at a minimum of 5 years.

  • All-cause mortality [ Time Frame: Min. 5 years ] [ Designated as safety issue: Yes ]
    Secondary outcome measures the incidence of all-cause mortality at a minimum of 5 years.

  • Costs and effectiveness [ Time Frame: Min. 5 years ] [ Designated as safety issue: No ]
    Secondary outcome measures total direct and indirect costs and cost-effectiveness at a minimum of 5 years.

  • Quality of life [ Time Frame: Min. 5 years ] [ Designated as safety issue: No ]
    Secondary outcome measures health-related quality of life at a minimum of 5 years.

  • Echocardiographic parameters [ Time Frame: Min. 5 years ] [ Designated as safety issue: No ]
    Secondary outcome measures echocardiographic parameters at a minimum of 5 years.

  • CMR parameters [ Time Frame: Min. 5 years. ] [ Designated as safety issue: No ]
    Secondary outcome measures Cardiovascular Magnetic Resonance imaging (CMR)parameters (left ventricular function, left atrial dimensions, pulmonary hypertension) at a minimum of 5 years.

  • Atrial fibrillation [ Time Frame: Min. 5 years ] [ Designated as safety issue: No ]
    Secondary outcome measures the incidence of asymptomatic atrial fibrillation at a minimum of 5 years.

  • Exercise test parameters [ Time Frame: Min. 5 years. ] [ Designated as safety issue: No ]
    Secondary outcome measures exercise test parameters at a minimum of 5 years.

  • BNP [ Time Frame: Min. 5 years ] [ Designated as safety issue: No ]
    Secondary outcome measures brain natriuretic peptide (BNP) plasma levels at a minimum of 5 years.


Other Outcome Measures:
  • Surgery complication rate [ Time Frame: Min. 5 years ] [ Designated as safety issue: Yes ]
    The complication rate in the mitral valve surgery group (e.g. re-operation for bleeding, pneumonia, residual or recurrent mitral valve regurgitation) will be determined at a minimum of 5 years.

  • Rate of surgery [ Time Frame: Min. 5 years ] [ Designated as safety issue: Yes ]
    Rate of surgery in the watchful waiting group will be determined at a minimum of 5 years.


Estimated Enrollment: 250
Study Start Date: February 2013
Estimated Study Completion Date: February 2021
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Early mitral valve repair
Early mitral valve repair
Procedure: Early mitral valve repair
Patients in the group of early mitral valve repair will be operated by way of routine mitral valve repair procedures in specialized centres.
Active Comparator: Watchful waiting
Watchful waiting
Other: Watchful waiting
In case of watchful waiting a conservative treatment is performed, based on close monitoring of the patient for clear signs of deterioration that triggers facilitated surgery before left ventricular dysfunction is present.

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].

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01708265

Contacts
Contact: Steven AJ Chamuleau, MD, PhD 0031 88 75 56176 S.A.J.Chamuleau@umcutrecht.nl
Contact: Jolanda Kluin, MD, PhD 0031 88 75 56179 J.Kluin@umcutrecht.nl

Locations
Netherlands
Leiden University Medical Center Not yet recruiting
Leiden, South Holland, Netherlands, 2333 ZA
Contact: Robert JM Klautz, prof. MD PhD    0031 71 526 4022    r.j.m.klautz@lumc.nl   
Principal Investigator: Robert JM Klautz, prof. MD PhD         
Sub-Investigator: Rosemarijn Jansen, MD         
University Medical Center Utrecht (UMC Utrecht) Recruiting
Utrecht, Netherlands, 3584 CX
Contact: Steven AJ Chamuleau, MD, PhD    0031 88 75 56176    S.A.J.Chamuleau@umcutrecht.nl   
Contact: Jolanda Kluin, MD, PhD    0031 88 75 56179    J.Kluin@umcutrecht.nl   
Principal Investigator: Steven AJ Chamuleau, MD, PhD         
Principal Investigator: Jolanda Kluin, MD, PhD         
Sub-Investigator: Rosemarijn Jansen, MD         
Sponsors and Collaborators
UMC Utrecht
Leiden University Medical Center
The Interuniversity Cardiology Institute of the Netherlands
WCN, Dutch Network for Cardiovascular Research
Investigators
Principal Investigator: Steven AJ Chamuleau, MD, PhD University Medical Center Utrecht (UMC Utrecht)
Principal Investigator: Jolanda Kluin, MD, PhD University Medical Center Utrecht (UMC Utrecht)
Principal Investigator: Robert JM Klautz, Prof. MD PhD Leiden University Medical Center (LUMC Leiden)
  More Information

Additional Information:
Publications:
Responsible Party: S.A.J. Chamuleau, MD, PhD, UMC Utrecht
ClinicalTrials.gov Identifier: NCT01708265     History of Changes
Other Study ID Numbers: NL39851.041.12.
Study First Received: October 11, 2012
Last Updated: February 5, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by UMC Utrecht:
Mitral Valve Insufficiency
Mitral Valve Regurgitation
Asymptomatic Mitral Valve Regurgitation
Asymptomatic Mitral Valve Insufficiency
Mitral Valve Repair
Watchful Waiting

Additional relevant MeSH terms:
Heart Valve Diseases
Mitral Valve Insufficiency
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on April 17, 2014