Phase 3
N=38
Molecular Mechanisms of Volume Overload-Aim 1(SCCOR in Cardiac Dysfunction and Disease)
Mitral Regurgitation
Bottom Line
View on ClinicalTrials.gov: NCT01052428 ↗Enrolled (actual)
38
Serious AEs
29.0%
Results posted
Apr 2012
Primary outcome: Primary: Left Ventricular End Diastolic Volume Indexed to Body Surface Area — 91.66; 95.74; 90.93; NA ml/m^2 — p=0.4568
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- metoprolol succinate (Toprol XL) (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 19+ yrs
- Sex
- All
- Sponsor
- University of Alabama at Birmingham
- Primary completion
- Jul 2010
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Left Ventricular End Diastolic Volume Indexed to Body Surface Area |
91.66; 95.74; 90.93; NA; 90.84; 95.24 | 0.4568 |
| PRIMARY Left Ventricular End-diastolic Mass Indexed to Left Ventricular End-diastolic Volume |
0.61; 0.61; 0.53; NA; 0.62; 0.6 | 0.1967 |
| PRIMARY Left Ventricular End-Diastolic Radius to Wall Thickness |
4.76; 4.69; 5.02; NA; 4.51; 4.85 | 0.55 |
| PRIMARY Left Ventricular End Systolic Volume Indexed to Body Surface Area |
34.01; 35.98; 32.83; NA; 32.53; 36.53 | 0.21 |
| PRIMARY Left Ventricular Ejection Fraction |
62.62; 62.09; 63.90; NA; 63.80; 61.29 | 0.006 sig |
| PRIMARY Systolic Longitudinal Strain |
87.94; 82.55; 115.07; NA; 45.90; 78.68 | 0.16 |
| PRIMARY Peak Early Filling Rate: Rate of Change Over Time |
2.27; 2.12; 2.58; NA; 2.38; 2.08 | 0.001 sig |
Summary
The investigators hypothesize that beta-1 receptor blockade (ß1-RB) attenuates extracellular matrix (ECM) degradation and progressive adverse Left Ventricular (LV) remodeling and failure in the volume overload of mitral regurgitation (MR). Patients without coronary artery disease and moderate MR, as assessed by color/flow Doppler echocardiography, will be randomized to ß1-RB vs. placebo to address the following aims:
*Aim 1: Establish whether ß1-RB attenuates adverse LV remodeling compared to placebo in patients with non-surgical, chronic MR. Using 3-dimensional magnetic resonance imaging (MRI) and tissue tagging, LV function and geometry will be assessed at baseline and every 6 months for up to 2 years.
Aim 2: Determine whether indices of inflammation correlate with degree of LV remodeling and whether ß1-RB decrease indices of inflammation and collagen turnover. At the time of MRI, blood samples for collagen breakdown products, matrix metalloproteinase (MMP) activity, and markers of excess production of reactive inflammatory species (RIS) will be obtained and related to changes in LV remodeling defined by serial 3-dimensional MRI and tissue tagging.
Eligibility Criteria
Inclusion Criteria:Patients who have Moderate MR documented by color flow doppler:
- LV ejection fraction > 55%; LV end-systolic dimension trace aortic regurgitation or mean gradient > 10 mmHg).
- Mitral stenosis (mean gradient >5 mmHg, valve area 2.5 mg/dl.
- Hypertension requiring medical treatment or renal artery stenosis.
- Severe comorbidity: liver disease, malignancy, collagen vascular, steroid requirement.
- Pregnancy (negative pregnancy test and effective contraceptive methods are required prior to enrollment of females of childbearing potential).
- Uncontrolled (rate > 120/min) or recent (<4 weeks) atrial fibrillation.
- Routine, regular use of anti-inflammatory medications.
Exclusion Criteria Related to MRI
- Severe claustrophobia.
- Presence of a pacemaker or non-removable hearing aid.
- Presence of metal clips in the body.
Data sourced from ClinicalTrials.gov (NCT01052428). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.