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

• ClinicalTrials.gov Identifier: NCT00166400
• Recruitment Status: Completed
• First Posted: September 14, 2005
• Last Update Posted: July 24, 2008
• Sponsor: Mayo Clinic
• Collaborator: AstraZeneca
• Information provided by: Mayo Clinic

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Heart Valve Diseases	Drug: metoprolol succinate	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Beta Blockade in Mitral Regurgitation
• Study Start Date: July 2004
• Actual Primary Completion Date: July 2007
• Actual Study Completion Date: July 2007

Arms and Interventions

Intervention Details:

• Drug: metoprolol succinate
  Treatment with potent beta-blockade titrated to the maximally tolerated dose.

Outcome Measures

Primary Outcome Measures :

1. Degree of mitral regurgitation, assessed as the regurgitant volume, at baseline and 12 months [ Time Frame: baseline & 12 months ]

Secondary Outcome Measures :

1. Left ventricular end-diastolic volume index at baseline and 12 months [ Time Frame: baseline & 12 months ]
2. Left atrial end-diastolic volume at baseline and at 12 months [ Time Frame: baseline & 12 months ]

Eligibility Criteria

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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).

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

AstraZeneca

Investigators

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

More Information

• Responsible Party: Dr. Maurice Sarano, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00166400
• Other Study ID Numbers: 960-04; IRUSMETO0047, IRB 960-04
• First Posted: September 14, 2005
• Last Update Posted: July 24, 2008
• Last Verified: July 2008

Additional relevant MeSH terms:

Mitral Valve Insufficiency; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Metoprolol; Anti-Arrhythmia Agents; Antihypertensive Agents; Sympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action