A Randomized Clinical Trial of Metoprolol in Participants With Mitral Regurgitation.

July 23, 2008 updated by: Mayo Clinic

Beta Blockade in Mitral Regurgitation

Mitral valve regurgitation (leakage of the mitral valve of the heart) is frequent and currently there is no specific medical therapy. Mitral regurgitation is a slowly progressive disease that frequently requires surgical treatment. This randomized clinical trial will use Metoprolol, a common beta-blocker medication, to determine if medical treatment impacts mitral valve disease progression.

Study Overview

Status

Completed

Conditions

Heart Valve Diseases

Intervention / Treatment

Drug: metoprolol succinate

Detailed Description

Background: Mitral regurgitation (MR) is frequent and its prevalence is increasing with aging of the population. Organic MR, due to primary valvular lesions has severe consequences determined by its degree, with left ventricular (LV) remodeling and dysfunction, left atrial (LA) enlargement, leading to poor clinical outcome. Surgery can eliminate MR, but carries notable risks and is not applicable to all patients. Recent animal data suggest that beta-blockade in organic MR has significant positive effect, particularly on LV remodeling. Therefore, chronically decreasing MR, protecting LV and LA with beta-blockade are major goals of medical therapy. However, effects of chronic oral beta-blockade of human MR are uncertain and recent practice guidelines underscored these gaps in knowledge and did not recommend beta-blockade of MR. Hence, a trial of treatment of organic MR is needed. A large trial with mortality-morbidity end-points is desirable but premature without knowledge of magnitude of mechanistic effects of beta-blockade. The improvement of these intermediate end-points, mechanistically linked to outcome, is measurable with non-invasive quantitative techniques and forms the basis of the present clinical trial proposal. Hypothesis: Chronic beta-blockade therapy using Metoprolol weighed against placebo produces a sustained reduction of the consequences of organic MR. Specific aims are that treatment improves a) degree of MR (decreases regurgitant volume, primary end-point), b) LV remodeling (decreases LV end-diastolic volume index, second end-point), and c) LA enlargement (decreases LA volume, third end-point) as compared to placebo. Population: Patients with MR organic (intrinsic valve disease), isolated (no other valve disease) d moderate (regurgitant volume *30 mL/beat). Methods: A randomized clinical trial, placebo controlled, double-blind, without crossover, of 12 months oral treatment with potent beta-blockade (Metoprolol XL 50 to 200mg QD) titrated to the maximally tolerated dose. The trial is preceded by an acute study to determine tolerance. End-points are measured by Doppler-Echocardiography for quantitation of MR (regurgitant volume) using combination of 3 simultaneous methods (quantitative Doppler, two-dimensional echocardiography, proximal flow convergence) and echocardiography for LV and LA volume measurement. In addition cardiopulmonary exercise testing will measure peak O2 consumption at baseline and follow-up. This study seeks to enroll a total of 60 patients. The analysis will be based on intention to treat and compare changes in regurgitant volume, LV end-diastolic volume index and LA volume measured after one year of treatment with active drug or placebo. The results of this clinical trial should provide strong evidence regarding medical treatment of patients with organic MR and define future strategies to minimize mortality and morbidity of organic MR.

Study Type

Interventional

Enrollment (Anticipated)

Phase

Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Minnesota
  - Rochester, Minnesota, United States, 55905
    - Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

Inclusion criteria: Patients a) 21 years old or older, with b) MR observed with color flow imaging, c) due to organic mitral valve disease demonstrated by Echocardiography (not normal valve as in functional or ischemic MR), c) isolated (no valve disease other than functional tricuspid regurgitation by Doppler-Echocardiography), d) pure (no mitral stenosis by Doppler-Echocardiography), e) quantifiable by Doppler-Echocardiography, f) of degree * moderate, defined as RVol * 30 mL/beat, g) occurring on native valves, h) with echocardiographic imaging allowing assessment of LA and LV, and i) asymptomatic (or mildly symptomatic but not considered as candidates for immediate surgery by their attending physician).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: Triple

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Degree of mitral regurgitation, assessed as the regurgitant volume, at baseline and 12 months Time Frame: baseline & 12 months	baseline & 12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Left ventricular end-diastolic volume index at baseline and 12 months Time Frame: baseline & 12 months	baseline & 12 months
Left atrial end-diastolic volume at baseline and at 12 months Time Frame: baseline & 12 months	baseline & 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Collaborators

AstraZeneca

Investigators

Principal Investigator: Maurice E Sarano, M.D., Mayo Clinic

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2004

Primary Completion (Actual)

July 1, 2007

Study Completion (Actual)