Dutch-AMR: Early Mitral Valve Repair Versus Watchful Waiting in Asymptomatic Patients With Severe Mitral Regurgitation

Mitral Regurgitation Clinical Trial

— Dutch-AMR  

Official title:

Dutch-AMR Study: Early Mitral Valve Repair Versus Watchful Waiting in Asymptomatic Patients With Severe Organic Mitral Regurgitation and Preserved Ejection Fraction: a Multicenter Registry Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03975998
• Other study ID #: 16/743
• Status: Recruiting
• Start date: October 2016
• Est. completion date: October 2031

Study information

• Verified date: June 2019
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Rationale:

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: in the study of Enriquez-Sarano et al. for instance, 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 [1]. 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 (50% at 10 years follow-up according to Rosenhek et al [2]), it has proven to be eventually associated with good perioperative and postoperative outcome when careful follow-up is being carried out [2].

Objective:

To compare early MV repair versus watchful waiting in asymptomatic patients with severe organic mitral valve regurgitation and preserved left ventricular function.

Study design:

Multicenter, registry trial.

Study population:

250 Asymptomatic patients (18-75 years old) with severe organic MV regurgitation and preserved left ventricular function. The current European Society of Cardiology (ESC) guidelines on Valvular Heart Disease will be applied [3]. These guidelines are also used in the Netherlands. Accordingly, patients with an indication for MV surgery will not be included.

Intervention:

Intervention will be early MV repair compared to a watchful waiting strategy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: October 2031
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 18-75 years.

• Asymptomatic patients. "Asymptomatic" is defined as absence of subjective limitations of exercise capacity or complaints expressed by the patient and confirmed by the treating cardiologist.

• Severe organic mitral valve regurgitation. "Severe organic mitral valve regurgitation" is defined as non-ischemic mitral valve regurgitation with an organic cause (intrinsic valve lesion) as determined by echocardiographic core-lab reading based on the criteria for definition of severe MR as issued by the ESC guidelines [4]. For practical reasons, referring cardiologists can use an ESC guidelines based index that was validated in the investigator's core-lab (Jansen et al, Practical echocardiographic semi-quantitative scoring system to determine severity of mitral regurgitation. Abstract presentation at ESC EUROECHO Congress 2011 and annual spring congress 2012 Netherlands Society of Cardiology).

• Preserved left ventricular function, "Preserved left ventricular function" is defined as left ventricular ejection fraction >60% and left ventricular end-systolic dimension <45 mm (no indexed value, measured by echocardiography).

• 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, either on 12-lead ECG or holter-monitoring.

• 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.

• Patients with moderate to severe kidney disease (estimated glomerular filtration rate (eGFR) less than 30 mL/min).

• Flail leaflet together with a left ventricular end systolic diameter (LVESD) =40 mm (no indexed value)

Related Conditions & MeSH terms

• Mitral Regurgitation
• Mitral Valve Insufficiency

Intervention

Procedure:
• Mitral valve repair
Minimally invasive repair of severe organic mitral regurgiation

Locations

Country	Name	City	State
Netherlands	Amsterdam Medical Center (AMC)	Amsterdam
Netherlands	Amphia Breda	Breda
Netherlands	Medisch Spectrum Twente (MST)	Enschede
Netherlands	Leiden University Medical Center (LUMC)	Leiden
Netherlands	Maastricht UMC	Maastricht
Netherlands	University Medical Center Utrecht (UMC Utrecht)	Utrecht

Sponsors (7)

Lead Sponsor	Collaborator
UMC Utrecht	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Amphia Hospital, Leiden University Medical Center, Maastricht University Medical Center, Medisch Spectrum Twente, Netherlands Heart Institute

Country where clinical trial is conducted

Netherlands, 

References & Publications (3)

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. Epub 2006 May 1. — View Citation

Vahanian A, Baumgartner H, Bax J, Butchart E, Dion R, Filippatos G, Flachskampf F, Hall R, Iung B, Kasprzak J, Nataf P, Tornos P, Torracca L, Wenink A; Task Force on the Management of Valvular Hearth Disease of the European Society of Cardiology; ESC Committee for Practice Guidelines. Guidelines on the management of valvular heart disease: The Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology. Eur Heart J. 2007 Jan;28(2):230-68. Epub 2007 Jan 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to event: cardiovascular mortality, congestive heart failure, hospitalization, class I or class IIa indication for MV surgery		5 years