The Dutch Asymptomatic Mitral Regurgitation Trial

Mitral Valve Insufficiency Clinical Trial

— Dutch AMR  

Official title:

Dutch AMR; Early Mitral Valve Repair Versus Watchful Waiting in Asymptomatic Patients With Severe Organic Mitral Regurgitation; a Multicenter, Randomised Trial.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01708265
• Other study ID #: NL39851.041.12.
• Status: Terminated
• Phase: N/A
• First received: October 11, 2012
• Last updated: November 22, 2016
• Start date: February 2013
• Est. completion date: February 2021

Study information

• Verified date: November 2016
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

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].

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: February 2021
• Est. primary completion date: February 2021
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diseases of Mitral Valve
• Heart Valve Diseases
• Heart; Disease, Mitral(Valve)
• Mitral Valve Insufficiency

Intervention

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.

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.

Locations

Country	Name	City	State
Netherlands	Amsterdam Medisch Centrum	Amsterdam
Netherlands	Amphia Hospital	Breda
Netherlands	Leiden University Medical Center	Leiden	South Holland
Netherlands	University Medical Center Utrecht (UMC Utrecht)	Utrecht

Sponsors (4)

Lead Sponsor	Collaborator
UMC Utrecht	Leiden University Medical Center, The Interuniversity Cardiology Institute of the Netherlands, WCN, Dutch Network for Cardiovascular Research

Country where clinical trial is conducted

Netherlands, 

References & Publications (6)

Chenot F, Montant P, Vancraeynest D, Pasquet A, Gerber B, Noirhomme PH, El Khoury G, Vanoverschelde JL. Long-term clinical outcome of mitral valve repair in asymptomatic severe mitral regurgitation. Eur J Cardiothorac Surg. 2009 Sep;36(3):539-45. doi: 10.1016/j.ejcts.2009.02.063. — View Citation

Enriquez-Sarano M, Avierinos JF, Messika-Zeitoun D, Detaint D, Capps M, Nkomo V, Scott C, Schaff HV, Tajik AJ. Quantitative determinants of the outcome of asymptomatic mitral regurgitation. N Engl J Med. 2005 Mar 3;352(9):875-83. — View Citation

Jansen R, Kluin J, Chamuleau SA. Research versus clinical practice in asymptomatic patients with severe organic mitral regurgitation and preserved LV function. J Am Coll Cardiol. 2014 Oct 14;64(15):1639-40. doi: 10.1016/j.jacc.2014.07.964. — View Citation

Ling LH, Enriquez-Sarano M, Seward JB, Orszulak TA, Schaff HV, Bailey KR, Tajik AJ, Frye RL. Early surgery in patients with mitral regurgitation due to flail leaflets: a long-term outcome study. Circulation. 1997 Sep 16;96(6):1819-25. — View Citation

Rosenhek R, Rader F, Klaar U, Gabriel H, Krejc M, Kalbeck D, Schemper M, Maurer G, Baumgartner H. Outcome of watchful waiting in asymptomatic severe mitral regurgitation. Circulation. 2006 May 9;113(18):2238-44. — View Citation

Tietge WJ, de Heer LM, van Hessen MW, Jansen R, Bots ML, van Gilst W, Schalij M, Klautz RJ, Van den Brink RB, Van Herwerden LA, Doevendans PA, Chamuleau SA, Kluin J. Early mitral valve repair versus watchful waiting in patients with severe asymptomatic organic mitral regurgitation; rationale and design of the Dutch AMR trial, a multicenter, randomised trial. Neth Heart J. 2012 Mar;20(3):94-101. doi: 10.1007/s12471-012-0249-y. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Surgery complication rate	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.	Min. 5 years	No
Other	Rate for the need of facilitated surgery	Rate for the need of facilitated surgery in the watchful waiting group will be determined at a minimum of 5 years.	Min. 5 years	No
Primary	Composite endpoint: cardiovascular mortality, congestive heart failure and hospitalization for nonfatal cardiovascular events	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.	Min. 5 years	Yes
Secondary	Cardiovascular mortality	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).	Min. 5 years	Yes
Secondary	Congestive heart failure	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).	Min. 5 years	Yes
Secondary	Hospitalization for nonfatal cardiovascular events	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).	Min. 5 years	Yes
Secondary	All-cause mortality	Secondary outcome measures the incidence of all-cause mortality at a minimum of 5 years.	Min. 5 years	No
Secondary	Costs and effectiveness	Secondary outcome measures total direct and indirect costs and cost-effectiveness at a minimum of 5 years.	Min. 5 years	No
Secondary	Health-related quality of life	Secondary outcome measures health-related quality of life at a minimum of 5 years.	Min. 5 years	No
Secondary	Echocardiographic parameters	Secondary outcome measures echocardiographic parameters at a minimum of 5 years.	Min. 5 years	No
Secondary	CMR parameters	Secondary outcome measures Cardiovascular Magnetic Resonance imaging (CMR) parameters at a minimum of 5 years.	Min. 5 years.	No
Secondary	Paroxysmal atrial fibrillation	Secondary outcome measures the incidence of paroxysmal atrial fibrillation at a minimum of 5 years.	Min. 5 years	No
Secondary	Exercise test parameters	Secondary outcome measures exercise test parameters at a minimum of 5 years.	Min. 5 years.	No
Secondary	BNP	Secondary outcome measures brain natriuretic peptide (BNP) plasma levels at a minimum of 5 years.	Min. 5 years	No
Secondary	Myocardial infarction	Secondary outcome measures the incidence of myocardial infarction at a minimum of 5 years.	Min. 5 years	No
Secondary	Pacemaker implantation	Secondary outcome measures the incidence of pacemaker implantation at a minimum of 5 years.	Min. 5 years	No
Secondary	Transient ischemic attack	Secondary outcome measures the incidence of transient ischemic attack (TIA) at a minimum of 5 years.	Min. 5 years	No
Secondary	Pulmonary embolism	Secondary outcome measures the incidence of pulmonary embolism at a minimum of 5 years.	Min. 5 years	No

External Links

•   Dutch AMR study homepage