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

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00166400
First received: September 12, 2005
Last updated: July 23, 2008
Last verified: July 2008
  Purpose

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 Intervention Phase
Heart Valve Diseases
Drug: metoprolol succinate
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Beta Blockade in Mitral Regurgitation

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Degree of mitral regurgitation, assessed as the regurgitant volume, at baseline and 12 months [ Time Frame: baseline & 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Left ventricular end-diastolic volume index at baseline and 12 months [ Time Frame: baseline & 12 months ] [ Designated as safety issue: No ]
  • Left atrial end-diastolic volume at baseline and at 12 months [ Time Frame: baseline & 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: July 2004
Study Completion Date: July 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: metoprolol succinate
    Treatment with potent beta-blockade titrated to the maximally tolerated dose.
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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
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
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: NCT00166400

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

No publications provided

Responsible Party: Dr. Maurice Sarano, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00166400     History of Changes
Other Study ID Numbers: 960-04, IRUSMETO0047, IRB 960-04
Study First Received: September 12, 2005
Last Updated: July 23, 2008
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Heart Valve Diseases
Mitral Valve Insufficiency
Heart Diseases
Cardiovascular Diseases
Metoprolol
Metoprolol succinate
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
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

ClinicalTrials.gov processed this record on July 24, 2014