Clinical trial NCT01708265: The Dutch Asymptomatic Mitral Regurgitation Trial
Official title: Dutch AMR; Early Mitral Valve Repair Versus Watchful Waiting in Asymptomatic Patients With Severe Organic Mitral Regurgitation; a Multicenter, Randomised Trial.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Heart; Disease, Mitral(Valve)
Diseases of Mitral Valve
Mitral Valve Insufficiency
Keywords: Mitral Valve Insufficiency
Mitral Valve Regurgitation
Asymptomatic Mitral Valve Regurgitation
Asymptomatic Mitral Valve Insufficiency
Mitral Valve Repair
Watchful Waiting
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Leiden University Medical Center
name: The Interuniversity Cardiology Institute of the Netherlands
name: WCN, Dutch Network for Cardiovascular Research
First posted: 2012-10-16
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 \[citation 5, 6\].

Eligibility 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)
* Flail leaflet together with a left ventricular end systolic diameter (LVESD) \>40 mm

Primary outcomes:
measure: Composite endpoint: cardiovascular mortality, congestive heart failure and hospitalization for nonfatal cardiovascular events
timeFrame: Min. 5 years
Secondary outcomes:
measure: Cardiovascular mortality
timeFrame: Min. 5 years
measure: Congestive heart failure
timeFrame: Min. 5 years
measure: Hospitalization for nonfatal cardiovascular events
timeFrame: Min. 5 years
measure: All-cause mortality
timeFrame: Min. 5 years
measure: Costs and effectiveness
timeFrame: Min. 5 years
measure: Health-related quality of life
timeFrame: Min. 5 years
measure: Echocardiographic parameters
timeFrame: Min. 5 years
measure: CMR parameters
timeFrame: Min. 5 years.
measure: Paroxysmal atrial fibrillation
timeFrame: Min. 5 years
measure: Exercise test parameters
timeFrame: Min. 5 years.
measure: BNP
timeFrame: Min. 5 years
measure: Myocardial infarction
timeFrame: Min. 5 years
measure: Pacemaker implantation
timeFrame: Min. 5 years
measure: Transient ischemic attack
timeFrame: Min. 5 years
measure: Pulmonary embolism
timeFrame: Min. 5 years
Other outcomes:
measure: Surgery complication rate
timeFrame: Min. 5 years
measure: Rate for the need of facilitated surgery
timeFrame: Min. 5 years
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: South Holland
city: Amsterdam
country: Netherlands
facility: Amsterdam Medisch Centrum
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht (UMC Utrecht)
Study officials:
affiliation: University Medical Center Utrecht (UMC Utrecht)
name: Steven AJ Chamuleau, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Utrecht (UMC Utrecht)
name: Jolanda Kluin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Leiden University Medical Center (LUMC Leiden)
name: Robert JM Klautz, Prof. MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1161/01.cir.96.6.1819.
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. doi: 10.1056/NEJMoa041451.
citation: 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. Epub 2009 Jul 25.
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. doi: 10.1161/CIRCULATIONAHA.105.599175. Epub 2006 May 1.
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.
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. No abstract available.