Determinants of the Progression and Outcome of Mitral Regurgitation (PROGRAM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Laval University
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Heart and Stroke Foundation of Canada
Information provided by (Responsible Party):
Philippe Pibarot, Laval University
ClinicalTrials.gov Identifier:
NCT01835054
First received: April 16, 2013
Last updated: NA
Last verified: April 2013
History: No changes posted
  Purpose

Mitral regurgitation (MR) is one of the most frequent valve lesions, both in North America and in Europe, and its prevalence is increasing owing to the aging of the population. There are 2 main categories of mitral regurgitation (MR): Organic Mitral Regurgitation (OMR) and Ischemic Mitral Regurgitation. Organic or primary MR is caused by am anatomic alteration of the valvular or subvalvular mitral apparatus and refers to rheumatic MR and degenerative MR that includes mitral leaflet prolapse and flail leaflet. In the past 20 years, degenerative MR has become, by far, the most frequent cause of severe MR leading to surgery in the western world. However, the best current treatment for OMR remains uncertain and controversial. This is, in large part, due to the lack of prospective data on the determinants of OMR progression and outcome. Furthermore, we have obtained preliminary data showing that OMR is a dynamic lesion. Hence, the echocardiographic evaluation of MR at rest, as generally performed during routine clinical exam, does not necessarily reflect the status of MR during patient's daily activities and thereby does not adequately assess the risk of rapid progression and poor outcome in these patients.

The general objective of this study is thus: to identify the independent predictors of disease progression and outcome in patients with asymptomatic chronic OMR.

The specific aims of the study are: (1) To obtain and analyze: a) the dynamic changes in MR severity, pulmonary arterial pressure, and LV function during exercise; b) the maximum exercise capacity; c) the metabolic profile; d) the plasma natriuretic peptides, e) the blood markers of myocardial extracellular matrix (ECM) turnover; f) the progression of MR severity and LV dysfunction during follow-up; and g) the occurrence of adverse clinical outcomes (i.e. symptoms, LV dysfunction, atrial fibrillation, pulmonary hypertension, heart failure, cardiovascular death) during follow-up in a series of 440 patients with at least moderate OMR and no symptoms at baseline. (2) To analyze the valve tissue samples explanted from the patients who will undergo mitral valve repair with quadrangular resection during follow-up in order to document the presence of lipids, inflammation, and expression of metalloproteinases (MMPs). (3) To obtain and analyze the postoperative changes in LV geometry and function, pulmonary arterial pressure, symptoms, and exercise capacity in the subset of patients who will undergo mitral valve surgery during follow-up. (4) To evaluate the usefulness of the exercise induced changes in MR severity, pulmonary arterial pressure, and LV function (i.e. contractile reserve), and of the blood levels of natriuretic peptides and ECM biomarkers for the prediction of rapid progression to LV dysfunction and adverse events. (5) To examine the relationship between the metabolic abnormalities linked to visceral obesity and the progression and outcome of OMR. (6) To determine, among the baseline clinical, echocardiographic, metabolic, and biomarkers variables, those which are independently associated with the progression of MR severity and LV dysfunction, and the occurrence of adverse clinical outcomes in patients with OMR.


Condition Intervention
Mitral Valve Insufficiency
Biological: blood sample
Genetic: DNA collection
Other: Doppler echocardiography
Other: Cardiopulmonary exercise testing
Other: Magnetic resonance imaging
Other: Exercise stress doppler echocardiography

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Determinants of the Progression and Outcome of Mitral Regurgitation

Resource links provided by NLM:


Further study details as provided by Laval University:

Primary Outcome Measures:
  • Combined clinical and echocardiographic endpoint [ Time Frame: Patients will be followed for 4 years ] [ Designated as safety issue: No ]
    Development of symptoms, left ventricular (LV) dysfunction (LV Ejection Fraction<60% and/or LV end diastolic diameter >40mm), atrial fibrillation or flutter, pulmonary arterial hypertension (resting systolic pressure >50mmHg), occurence of pulmonary oedema, congestive heart failure or cardiovascular death


Secondary Outcome Measures:
  • Progression of MR severity [ Time Frame: Patients will be followed for 4 years ] [ Designated as safety issue: No ]
    The annualized progression rate of MR severity will be calculated as the difference between effective regurgitant orifice, regurgitant volume, and vena contracta width measured at baseline and those measured at the last follow-up divided by the time between the first and last examinations.

  • Progression of pulmonary arterial hypertension [ Time Frame: Patients will be folowed for 4 years ] [ Designated as safety issue: No ]
    The annualized progression rate of resting systolic pulmonary arterial pressure will be calculated.

  • Progression of LV dysfuntion [ Time Frame: Patients will be followed for 4 years ] [ Designated as safety issue: No ]
    The annualized progression rate of LVEF, LV end-systolic dimension, and LV myocardial global peak systolic velocities and strain will be calculated.

  • Maximum exercise capacity at baseline [ Time Frame: Patients will be followed for 4 years ] [ Designated as safety issue: No ]
    Maximum exercise capacity at baseline as measured by the percentage of age and gender predicted VO2max. We will determine which are, among the clinical and Doppler-echocardiographic variables, the independent determinants of maximum exercise capacity at baseline. The baseline exercise capacity will also be used as an independent variable, i.e. we will determine if it is an independent predictor of the primary end-point and of the other secondary end-points


Biospecimen Retention:   Samples With DNA

Fasting blood sample (serum, lithium-heparin, EDTA) and white cells - Tissue (explanted mitral valves)


Estimated Enrollment: 440
Study Start Date: December 2008
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Patients with mitral regurgitation

At study entry, patients have 1) a clinical assessment including metabolic risk profile 2) a blood sample for analysis of metabolic, cardiac neurohormonal biomarkers and DNA collection 3) a complete rest doppler echocardiography 4) an exercise stress doppler echocardiography 5) a cardiopulmonary exercise testing and 6) a magnetic resonance imaging.

At follow-up, patients have 1) a clinical and clinical events assessment 2) a blood sample analysis 3) a resting echocardiography every year.

Biological: blood sample Genetic: DNA collection Other: Doppler echocardiography Other: Cardiopulmonary exercise testing Other: Magnetic resonance imaging Other: Exercise stress doppler echocardiography

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Cohort will be selected at primary care clinic

Criteria

Inclusion Criteria:

  • Age >21 years
  • Presence of at least moderate chronic OMR defined as an ERO ≥20mm2 and/or a regurgitant volume ≥30mL

Exclusion Criteria:

  • MR due to ischemic heart disease or cardiomyopathy
  • > mild mitral stenosis, aortic regurgitation, aortic stenosis or pulmonary stenosis
  • previous valve operation
  • history of myocardial infarction or angiographycally documented coronary stenosis
  • congenital or pericardial heart disease
  • endocarditis
  • contra-indication or inability to exercise
  • pregnancy
  • Class I or II indication for mitral valve operation according to the 2006-2007 ACC/AHA/ESC guidelines
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01835054

Contacts
Contact: Philippe Pibarot, PhD, DVM 418-656-8711 ext 5938 Philippe.Pibarot@med.ulaval.ca
Contact: Haifa Mahjoub, MD, PhDs 418-656-8711 ext 2647 haifa.mahjoub@criucpq.ulaval.ca

Locations
Belgium
University Hospital of Sart Tilman Recruiting
Liège, Belgium, 4000
Contact: Patrizio Lancellotti, MD, PhD    32(0)4/366 7194    plancellotti@chu.ulg.ac.be   
Principal Investigator: Patrizio Lancellotti, MD, PhD         
Sub-Investigator: Julien Magne, PhD         
Canada, Quebec
Institut Universitaire de Cardiologie et de Pneumologie de Québec Recruiting
Québec, Quebec, Canada, G1V4G5
Contact: Philippe Pibarot, PhD, DVM    418-656-8711 ext 5938    Philippe.Pibarot@med.ulaval.ca   
Contact: Haifa Mahjoub, MD, PhDs    418-656-5711 ext 2647    haifa.mahjoub@criucpq.ulaval.ca   
Principal Investigator: Philippe Pibarot, PhD, DVM         
France
University Hospital of Rennes Active, not recruiting
Rennes, France, 35033
Sponsors and Collaborators
Laval University
Canadian Institutes of Health Research (CIHR)
Heart and Stroke Foundation of Canada
Investigators
Principal Investigator: Philippe Pibarot, PhD, DVM Institut Universitaire de Cardiologie et de Pneumologie de Québec
  More Information

Publications:

Responsible Party: Philippe Pibarot, Doctor, Laval University
ClinicalTrials.gov Identifier: NCT01835054     History of Changes
Other Study ID Numbers: MOP#102737
Study First Received: April 16, 2013
Last Updated: April 16, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by Laval University:
Mitral regurgitation
Mitral valve prolapse
Echocardiography, Doppler
Stress echocardiography
Cardiopulmonary exercice testing
Magnetic Resonance Imaging
Cardiac neurohormones
Visceral obesity
Cardiometabolic risk
Risk stratification

Additional relevant MeSH terms:
Mitral Valve Insufficiency
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 14, 2014