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Mitral RegurgitationRIPCOM1NCT03155373

The Right Ventricular Pulmonary Circulation Continuum in Mitral Valve Disease Study

An observational study of Mitral Regurgitation and Pulmonary Hypertension, run by Imperial College London at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Mitral Regurgitation, Pulmonary Hypertension
What is being tested?
Cardiac catheterisation, Cardiopulmonary exercise testing and Pulmonary function tests
Type of treatment
Surgery or procedure
How many people
50 participants
Where
1 siteUnited Kingdom
Study dates
15 Feb 2017to 1 Mar 2019
Phase
Observational
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Patients undergoing cardiac surgery for severe primary/degenerative mitral regurgitation under the current guidelines.

Who may be able to join

  • Patients listed for surgery for severe primary mitral regurgitation +/- concomitant coronary artery bypass grafting for bystander disease +/- tricuspid valve surgery +/- atrial fibrillation surgery.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site
  • Hammersmith Hospital

    London, W12 0HS

Other trials in United Kingdom

About this study

Official title: 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.

Read the 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).

Being tested
Cardiac catheterisation, Cardiopulmonary exercise testing, Pulmonary function tests, Cardiac MRI, Quality of life survey
Keywords
Cardiopulmonary exercise testing
Medical subject headings
Mitral Valve Insufficiency, Hypertension, Pulmonary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cardiac catheterisationDiagnostic test

    Pre-operative left heart catheterisation +/- right heart catheterisation

  • Cardiopulmonary exercise testingDiagnostic test

    Pre and post-operative cardiopulmonary exercise testing

  • Pulmonary function testsDiagnostic test

    Pre and post-operative pulmonary function tests

  • Cardiac MRIDiagnostic test

    Pre and post-operative cardiac MRI

  • Quality of life surveyOther

    Pre and post-operative quality of life survey (SF36)

  • Mitral valve operationProcedure or surgery

    Clinically indicated mitral valve repair/replacement +/- coronary artery surgery +/- tricuspid valve surgery +/- atrial fibrillation surgery

  • Myocardial biopsiesProcedure or surgery

    Right and left epicardial ventricular biopsies taken at time of clinically indicated surgery

Study groups in NCT03155373
Study groupRoleWhat they receive
AAsymptomatic/mild symptomatic patients with normal pre-operative left ventricular function (defined as left ventricular ejection fraction >60%)
Receives: Diagnostic Test: Cardiac catheterisation; Diagnostic Test: Cardiopulmonary exercise testing; Diagnostic Test: Pulmonary function tests; Diagnostic Test: Cardiac MRI; Other: Quality of life survey; Procedure: Mitral valve operation; Procedure: Myocardial biopsies
BSymptomatic patients with normal pre-operative left ventricular function (defined as left ventricular ejection fraction greater than or equal to 60%)
Receives: Diagnostic Test: Cardiac catheterisation; Diagnostic Test: Cardiopulmonary exercise testing; Diagnostic Test: Pulmonary function tests; Diagnostic Test: Cardiac MRI; Other: Quality of life survey; Procedure: Mitral valve operation; Procedure: Myocardial biopsies
CPatients with impaired pre-operative left ventricular function (defined as left ventricular ejection fraction <60%)
Receives: Diagnostic Test: Cardiac catheterisation; Diagnostic Test: Cardiopulmonary exercise testing; Diagnostic Test: Pulmonary function tests; Diagnostic Test: Cardiac MRI; Other: Quality of life survey; Procedure: Mitral valve operation; Procedure: Myocardial biopsies

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Impaired Post-operative Functional Capacity

    Dichotomic variable of post-operative left ventricular ejection < 50% and/or post-operative percentage predicted peak VO2 <= 84%

    Measured: 1 year

  2. Imaging Data

    Correlation between transthoracic echocardiogram and cardiac MRI parameters

    Measured: 1 year

Secondary outcomes (3)
  1. Right Heart Catheterisation

    Accuracy of measurements of pre-op pulmonary artery pressures against the gold standard of right heart catheterisation

    Measured: Pre-op

  2. Quality of Life as Assessed by SF36 Survey

    Changes in quality of life measured on the SF36 survey after surgery

    Measured: Baseline (preoperatively), early follow up (6 weeks after surgery), late follow up (6 months after surgery)

  3. Myocardial Histology

    Quantification of myocardial fibrosis on right and left ventricular biopsies

    Measured: At surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2017
  2. Study start15 Feb 2017
  3. Primary completion1 Mar 2019
  4. Study completion1 Mar 2019

Resources

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
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03155373
Sponsor's protocol ID
16HH3639
Other IDs
16/LO/2127, 199676
Acronym
RIPCOM1
Status last verified
Feb 2023
First submitted
15 May 2017
Last updated
28 Feb 2023
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Afoke J, Gibbs S, Kanaganayagam S, Bruno D, Howard L, Punjabi P. Changes in cardiopulmonary exercise testing variables after surgery for primary mitral regurgitation. Perfusion. 2026 Mar;41(2):165-172. doi: 10.1177/02676591251346035. Epub 2025 May 27.

    PubMed 40424530

Questions about this trial

What is this clinical trial studying?

An observational study of Mitral Regurgitation and Pulmonary Hypertension, run by Imperial College London at 1 site in United Kingdom.

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 1 inclusion and 2 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: finished, as of the sponsor's last update on 28 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. 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?

Yes. Results are posted in the registry (first posted 28 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Impaired Post-operative Functional Capacity (time frame: 1 year). The study lists 2 primary outcomes in all. 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 NCT03155373, which also lists 1 linked publication.

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 28 Feb 2023.

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RIPCOM1 Clinical Trial NCT03155373 | AzTrials