Mitral RegurgitationDutch-AMRNCT03975998
Dutch-AMR: Early Mitral Valve Repair Versus Watchful Waiting in Asymptomatic Patients With Severe Mitral Regurgitation
An observational study of Mitral Regurgitation, run by UMC Utrecht at 6 sites in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Mitral Regurgitation
- What is being tested?
- Mitral valve repair
- Type of treatment
- Surgery or procedure
- How many people
- 500 participants
- Where
- 6 sitesNetherlands
- Study dates
- Oct 2016to Oct 2031
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Asymptomatic patients with severe organic mitral regurgitation and preserved ejection fraction.
Who may be able to join
- 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.
Who cannot join
- 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)
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
Netherlands6 sites, 5 recruiting
- Recruiting
Amsterdam Medical Center (AMC)
Amsterdam
Matthijs Boekholdt, s.m.boekholdt@amsterdamumc.nl
Jolanda Kluin
- Recruiting
Amphia Breda
Breda
Jeroen Schaap, jschaap@amphia.nl
Jeroen Schaap, MD
- Recruiting
Medisch Spectrum Twente (MST)
Enschede
Lodewijk Wagenaar, L.Wagenaar@mst.nl
Lodewijk Wagenaar
- Active, not recruiting
Leiden University Medical Center (LUMC)
Leiden
- Recruiting
Maastricht UMC
Maastricht
Bas Streukens, bas.streukens@mumc.nl
- Recruiting
University Medical Center Utrecht (UMC Utrecht)
Utrecht, 3584 CX
Steven AJ Chamuleau, MD, PhD, 0031 88 75 59801, S.A.J.Chamuleau@umcutrecht.nl
Steven AJ Chamuleau, MD, PhD
About this study
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
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.
Read more
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.
- Conditions
- Mitral Regurgitation
- Being tested
- Mitral valve repair
- Keywords
- Mitral regurgitation, Mitral repair, Watchful waiting, Asymptomatic
- Medical subject headings
- Mitral Valve Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mitral valve repairProcedure or surgery
Minimally invasive repair of severe organic mitral regurgiation
| Study group | Role | What they receive |
|---|---|---|
| Aymptomatic patients with severe mitral regurgitation | Watchful waiting Early Surgery Receives: Procedure: Mitral valve repair |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to event: cardiovascular mortality, congestive heart failure, hospitalization, class I or class IIa indication for MV surgery
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2019
- Study startOct 2016
- Primary completionOct 2026 (estimated)
- Study completionOct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Mitral RegurgitationStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 500 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Collaborators
- Netherlands Heart Institute, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Amphia Hospital, Maastricht University Medical Center, Medisch Spectrum Twente, Leiden University Medical Center
- Responsible party
- Principal investigator, S.A.J. Chamuleau, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03975998
- Sponsor's protocol ID
- 16/743
- Acronym
- Dutch-AMR
- Status last verified
- Jun 2019
- First submitted
- 28 Nov 2016
- Last updated
- 6 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 9323067Rosenhek 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.
PubMed 16651470Vahanian 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. doi: 10.1093/eurheartj/ehl428. Epub 2007 Jan 26. No abstract available.
PubMed 17259184
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03975998
- Acronym / sponsor ID
- Dutch-AMR / 16/743
- Conditions
- Mitral Regurgitation
- Keywords
- Mitral regurgitation, Mitral repair, Watchful waiting, Asymptomatic
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Collaborators
- Netherlands Heart Institute, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Amphia Hospital, Maastricht University Medical Center, Medisch Spectrum Twente, Leiden University Medical Center
- Study start
- Oct 2016
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Oct 2031 (estimated)
- First posted
- 5 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 5 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Aymptomatic patients with severe mitral regurgitation | – | Procedure: Mitral valve repairWatchful waiting Early Surgery |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Asymptomatic patients with severe organic mitral regurgitation and preserved ejection fraction.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mitral valve repairMinimally invasive repair of severe organic mitral regurgiation | Procedure or surgery | Aymptomatic patients with severe mitral regurgitation |
Primary outcome
Time to event: cardiovascular mortality, congestive heart failure, hospitalization, class I or class IIa indication for MV surgery
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2019.
- Background: PubMed 9323067Ling 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.
- Background: PubMed 16651470Rosenhek 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.
- Background: PubMed 17259184Vahanian 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. doi: 10.1093/eurheartj/ehl428. Epub 2007 Jan 26. No abstract available.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mitral Regurgitation, run by UMC Utrecht at 6 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to event: cardiovascular mortality, congestive heart failure, hospitalization, class I or class IIa indication for MV surgery (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03975998, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2019.