- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03155373
The Right Ventricular Pulmonary Circulation Continuum in Mitral Valve Disease Study (RIPCOM1)
The Right Ventricular Pulmonary Circulation Continuum in Mitral Valve Disease
Mitral regurgitation (MR) is a prevalent valvular heart pathology. Indications for surgery include symptoms, impaired left ventricular function or enlarging dimensions, new onset atrial fibrillation, pulmonary hypertension, asymptomatic status with a high likelihood of success.
Asymptomatic severe primary MR can be initially monitored without impairing long term survival. However, significant symptoms or impairment of left ventricular function is associated with worse prognosis due to long term heart failure. Some physicians wait for early symptoms before referring for surgery and this is reflected by a great variation in referral patterns, but symptomatic status is subjective and difficult to assess. Nearly all of the surgical indications are based on expert opinion rather than significant evidence base.
The primary aim of this project is to improve the current guidelines for surgery for primary MR by finding an objective marker of functional capacity which correlates with surrogates of prognosis and detects early decline, but returns to normal after surgery.
Study Overview
Status
Conditions
Detailed Description
The current indications for surgery for MR include symptomatic status; asymptomatic status with echocardiographic features such as impaired left ventricular function or increased left ventricular dimensions; new onset atrial fibrillation or pulmonary hypertension; asymptomatic status with a high likelihood of durable repair and low co-morbidity. The limitation in strength of the current evidence base is reflected by the class of evidence being expert opinion (level C) for all of the above indications with the sole exception of symptomatic patients, which is level B.
The fulcrum point between asymptomatic status and symptomatic status at which patients would derive prognostic benefit and thus should be referred for surgery on prognostic grounds still remains unclear and controversial. Although elective mitral valve repair carries a low risk of mortality, it has been demonstrated that asymptomatic patients with severe degenerative MR can be safely followed up before becoming symptomatic or reaching cutoff values for left ventricular dimensions, size or pulmonary hypertension; with no significant difference with expected survival. As a result, it is debatable whether prophylactic surgery for all patients with asymptomatic severe degenerative MR derives prognostic benefit.
At the other end of the clinical spectrum, the increased operative mortality and worse long term prognosis of symptomatic patients is well proven. Patients with New York Heart Association Class III or IV status have excessive operative mortality and significantly increased mortality at 10 years. Both this study and another have demonstrated that preoperative ejection fraction is an independent predictor of long term survival. Although this evidence base does not support prophylactic surgery on asymptomatic patients, it does highlight the importance of avoiding the long term sequelae of MR in causing symptomatic status or left ventricular impairment. Hence attention has turned to objective markers or investigations independent of symptomatic status that may be subjectively assessed in the early phases; to help identify patients who would prognostically benefit from earlier surgical intervention.
In summary, severe mitral regurgitation is a common valvular pathology that causes a significant burden of disease. Current guidelines for timing of operative intervention are mostly based on expert opinion rather than randomised trials or studies. The ideal tipping point investigation will be an objective marker of functional capacity which correlates with known surrogates of survival such as left ventricular function; and detects early decline, but returns to normal after successful surgery. The improved evidence base will create an epidemiological shift in patterns of referring for mitral valve surgery and reduce the burden of disease of heart failure.
Patients will undergo the following investigations:
Right heart catheterisation- It is the usual gold standard practice at our institution for patients to have a right heart catheterisation before being referred for surgery. Those who have not had one may be referred to the Department of Cardiology at Hammersmith Hospital for this test.
Cardiac MRI- patients will have a T1 weighted cardiac MRI. One strength of cardiac MRI over transthoracic echocardiogram is objective measurements of right heart function. Parameters measured will be ventricular ejection fraction and dimensions, patterns of myocardial fibrosis.
Cardiopulmonary exercise testing (CPEX)- CPEX is a quantitative and validated method of assessing cardiorespiratory function and exercise capacity with commonly measured variables including maximal oxygen consumption (VO2 max) and the clearance of carbon dioxide during exercise (Ve/VCO2). The patient's gaseous exchange is monitored during a 3 minute rest period, a three minute "rolling basal" period when they perform exercise on a bicycle with no load; and subsequently during the exercise phase when the work load increases at a rate of 30 Watts per minute. Exercise continues until the patient has to stop or achieves predicted maximum heart rate.
Pulmonary function tests- Patients will have routine spirometry tests and also assessment of transfer factor.
Transthoracic echocardiogram- It is normal practice for patients to have an echocardiogram at preassessment clinic to assess biventricular function, dimensions and cardiac structural disease.
Quality of life questionnaire- Patients will be asked to fill out a validated questionnaire (SF-36 health survey).
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
-
London, United Kingdom, W12 0HS
- Hammersmith Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
Patients listed for surgery for severe primary mitral regurgitation +/- concomitant coronary artery bypass grafting for bystander disease +/- tricuspid valve surgery +/- atrial fibrillation surgery.
Exclusion Criteria:
Secondary mitral regurgitation. Significant history of ischaemic heart disease eg. angina. Age <18 years or >85 years. Critical preoperative status with multi-organ dysfunction. Emergency cardiac surgical intervention. Pregnancy. Unable to give informed consent or unwilling to participate in research. Patients with definite contraindication for MRI would be excluded from the cardiac MRI element of the study.
Patients we are unable to take adequate biopsies due to technical difficulties would be excluded from the myocardial biopsy element of the study.
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
A
Asymptomatic/mild symptomatic patients with normal pre-operative left ventricular function (defined as left ventricular ejection fraction >60%)
|
Pre-operative left heart catheterisation +/- right heart catheterisation
Pre and post-operative cardiopulmonary exercise testing
Pre and post-operative pulmonary function tests
Pre and post-operative cardiac MRI
Pre and post-operative quality of life survey (SF36)
Clinically indicated mitral valve repair/replacement +/- coronary artery surgery +/- tricuspid valve surgery +/- atrial fibrillation surgery
Right and left epicardial ventricular biopsies taken at time of clinically indicated surgery
|
B
Symptomatic patients with normal pre-operative left ventricular function (defined as left ventricular ejection fraction greater than or equal to 60%)
|
Pre-operative left heart catheterisation +/- right heart catheterisation
Pre and post-operative cardiopulmonary exercise testing
Pre and post-operative pulmonary function tests
Pre and post-operative cardiac MRI
Pre and post-operative quality of life survey (SF36)
Clinically indicated mitral valve repair/replacement +/- coronary artery surgery +/- tricuspid valve surgery +/- atrial fibrillation surgery
Right and left epicardial ventricular biopsies taken at time of clinically indicated surgery
|
C
Patients with impaired pre-operative left ventricular function (defined as left ventricular ejection fraction <60%)
|
Pre-operative left heart catheterisation +/- right heart catheterisation
Pre and post-operative cardiopulmonary exercise testing
Pre and post-operative pulmonary function tests
Pre and post-operative cardiac MRI
Pre and post-operative quality of life survey (SF36)
Clinically indicated mitral valve repair/replacement +/- coronary artery surgery +/- tricuspid valve surgery +/- atrial fibrillation surgery
Right and left epicardial ventricular biopsies taken at time of clinically indicated surgery
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Impaired Post-operative Functional Capacity
Time Frame: 1 year
|
Dichotomic variable of post-operative left ventricular ejection < 50% and/or post-operative percentage predicted peak VO2 <= 84%
|
1 year
|
Imaging Data
Time Frame: 1 year
|
Correlation between transthoracic echocardiogram and cardiac MRI parameters
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Right Heart Catheterisation
Time Frame: Pre-op
|
Accuracy of measurements of pre-op pulmonary artery pressures against the gold standard of right heart catheterisation
|
Pre-op
|
Quality of Life as Assessed by SF36 Survey
Time Frame: Baseline (preoperatively), early follow up (6 weeks after surgery), late follow up (6 months after surgery)
|
Changes in quality of life measured on the SF36 survey after surgery
|
Baseline (preoperatively), early follow up (6 weeks after surgery), late follow up (6 months after surgery)
|
Myocardial Histology
Time Frame: At surgery
|
Quantification of myocardial fibrosis on right and left ventricular biopsies
|
At surgery
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Prakash Punjabi, FRCS, Imperial College London
- Principal Investigator: Simon Gibbs, FRCP, Imperial College London
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 16HH3639
- 16/LO/2127 (Other Identifier: REC)
- 199676 (Other Identifier: IRAS)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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