To compare early mitral valve repair versus watchful waiting.
ID
Source
Brief title
Condition
- Cardiac valve disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome will be calculated as *time to first event*. The primary
outcome measures 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.
* the occurrence of:
- congestive heart failure or atrial fibrillation in the watchful waiting arm
resulting in a class I or
class IIa indication for elective MV surgery; and
- post-operative congestive heart failure or atrial fibrillation or reoperation
within 30 days after elective MV surgery (likely to be related to MV surgery
and not directly life threatening)
will not be considered as an endpoint.
Death is cardiovascular mortality, unless you can prove there is another cause
for death.
Congestive heart failure is the clinical diagnosis of heart failure and/or
requiring diuretics medication. According to the World Health Organisation
(WHO) definition, we explain stroke by "rapidly developing clinical signs of
focal (or global) disturbance of cerebral function, with symptoms lasting 24
hours or longer or leading to death, with no apparent cause other than of
vascular origin". Permanent atrial fibrillation (AF) is defined as AF present
for >24 hours.
Secondary outcome
- 'Key secondary outcome' inlcudes the separate components of the composite
primary endpoint:
cardiovascular mortality, congestive heart failure and hospitalization for
nonfatal cardiovascular events. divided in the endpoints:
stroke/cerebrovascular accident (CVA), AF (permanent or requiring
hospitalization) and reoperation after elective MV repair.
A detailed description of the components *cardiovascular mortality*,
*congestive heart failure* and hospitalization for nonfatal cardiovascular
events* is given in the definition of the primary outcome.
- 'Explorative secondary outcome' measures the outcome of the separate
components:
incidence of all-cause mortality, incidence of myocardial infarction, incidence
of pacemaker implantation, incidence of transient ischemic attack (TIA),
incidence of pulmonary embolism, total direct and indirect costs,
cost-effectiveness, health-related quality of life, echocardiographic and
cardiac magnetic resonance (CMR) parameters, exercise test parameters,
paroxysmal atrial fibrillation (AF present for <24 hours) and BNP levels.
Myocardial infarction is defined as angina pectoris together with a rise in
biomarkers (troponin) and ECG changes. For the definition of TIA symptoms need
to be determined by a neurologist and established on imaging.
Additionally, complication rates in the surgery group (e.g. re-operation for
bleeding, pneumonia, residual or recurrent mitral valve regurgitation) and rate
of surgery in the watchful waiting group will be determined.
Background summary
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 mitral valve replacement) in order to
prevent future LV dysfunction and complaints.
A number of non-randomised trials show a favourable outcome of early surgery.
At the other hand, non-randomised trials describe also that a conservative
strategy (i.e. watchful waiting) can be safely accomplished and has proven to
be eventually associated with good perioperative and postoperative outcome when
careful follow-up is being carried out.
Non-randomised trials inherently have a number of drawbacks; therefore a
randomised trial comparing the two treatment strategies is highly needed.
Study objective
To compare early mitral valve repair versus watchful waiting.
Study design
Multicenter prospective randomised trial.
Patients who provide informed consent will be randomly assigned to either: 1)
watchful waiting; 2) early MV repair.
At baseline, like in routine clinical assessment, an echocardiography, holter
registration, exercise test and routine laboratory testing (e.g. BNP) will be
performed. Furthermore patients will undergo CMR and fill in a QOL
questionnaire. Echocardiographic and CMR core-lab reading is planned to assess
(1) severity of MR and (2) left ventricular function.
Follow-up in both groups will be 5 years at least and according to clinical
practice, as recommended by the ESC guidelines. Apart from clinical practice by
the own treating cardiologist (standard care), at 1 year (+/- 3 weeks), 3 years
(+/- 3 weeks) and 5 years (+/- 3 weeks) study related visits will take place
in one of the study centers, including an echocardiography, holter registration
exercise test, routine laboratory testing (BNP) and QOL forms. After 5 years
(+/- 3 weeks) echocardiography and CMR are repeated, including core-lab
reading.
Every 6 months (+/- 3 weeks) a telephone consultation with the patient will
take place. Furthermore, a QOL form is sent to the patient 5x during follow-up.
Additional patient*s information from referring centres will be collected by
the researcher if necessary.
Intervention
Intervention will be early MV repair compared to a watchful waiting strategy.
Study burden and risks
All patients will be treated according to current ESC guidelines. As a result,
the increased peri-procedural risk of surgery will be weighed against known
outcome. Participation in this study implicates that patients will be
randomised to either early prophylactic surgery (early MV repair) or will be
treated conservatively (watchful waiting) and if necessary undergo facilitated
surgery. Most important, patients that are allocated to the surgery group are
inherently exposed to the surgical risk of MV repair (operative 30-day
mortality ranging from 0 to 2.8%). The heart team will exclude patients that
have higher expected surgical risks in advance, so before randomisation.
Potentially, the conservative group is exposed to deterioration of the left
ventricular function possibly related to medical treatment and/or
hospitalization and the possibility of a less repairable valve and/or higher
risk of surgery, while waiting to fulfil the guidelines criteria for surgery.
At present, no data are available in literature that indicate these risks.
Follow-up of the patient cohort is similar to routine daily practice. Next to
routine clinical practice, extra follow-up visits are planned in view of the
trial at the study centre at baseline, 12 months (+/- 3 weeks), 36 months (+/-
3 weeks) and 60 months (+/- 3 weeks), including echocardiography,
holter-monitoring, exercise testing, core lab reading and completing a
questionnaires including quality of life form (QOL). Rare but serious
complications in exercise testing are reported in one out of ten thousand
patients, which can be easily stratified in advance based on resting ECG,
medical history and risk factors. Additional diagnostic testing includes blood
examination (BNP) which requires a venous puncture and a CMR with contrast at
baseline and at 5 years (+/- 3 weeks). CMR provides no other side effects,
although it is contra-indicated in patients with metallic implants and
claustrophobic or pregnant patients. Metallic implants, claustrophobia,
pregnancy and moderate to severe kidney disease are no exclusion criteria for
study participation.
Gadolinium administration can lead to mild, mostly self-limiting, reactions in
<1%. Nevertheless, in patients with moderate to severe kidney disease
(estimated glomerular filtration rate (eGFR) less than 30 mL/min) contrast
administration has been rarely associated with the syndrome of nephrogenic
systemic fibrosis. It is recommended that gadolinium-based imaging be avoided
in such patients. Therefore we will exclude patients with moderate to severe
kidney disease from study participation.
In case of venous puncture there will be a very small risk of excessive
bleeding, fainting, dizziness, hematoma and infection.
Regardless low risks associated with exercise testing, CMR (including contrast
administration) and venous puncture, no extra burden, risk or benefit is
associated with the study participations compared to non-participating
patients. It can be concluded that the risk assessment for the patients
included in the Dutch AMR trial can be considered to be a moderate risk.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
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 mitral regurgitation as issued by the ESC guidelines. For practical reasons, referring cardiologists can use a ESC guidelines based index that was validated in our 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.
- 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 advanve, 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
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL39851.041.12 |