Angiotensin Converting Enzyme Inhibition in Children With Mitral Regurgitation

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of angiotensin converting enzyme inhibition (ACE-I) therapy for the treatment of mitral regurgitation (MR).

Detailed Description
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BACKGROUND: MR causes volume overload and hemodynamic burden on the left ventricle. Initial compensatory mechanisms may fail, leading to increased severity. Patients who have had repair of an atrioventricular septal defect (AVSD) are selected for this study as they have a relatively high incidence of moderate MR and their regurgitant orifice is mobile and dynamic, contributing to the likelihood that they might respond to medical therapy. DESIGN NARRATIVE: This is a randomized, double-blind, placebo-controlled trial of ACE-I therapy in children less than 18 years of age with at least moderate MR who are at least 6 months postoperative from repair of an AVSD. A non-randomized Observational Phase enrolled 181 children who were less than 6 months postoperative from repair of an AVSD, who were then evaluated at 6 months for trial eligibility.

Official Title
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Trial of ACE Inhibition in Children With Mitral Regurgitation After Repair of AVSD

Conditions
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Heart Defects, Congenital, Heart Septal Defects, Ventricular, Heart Failure, Congestive

Intervention / Treatment
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* Drug: Enalapril
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children less than 18 years of age and at least 6 months post AVSD repair or reoperation At least moderate MR Asymptomatic or minimally symptomatic, defined by Ross Heart Failure Class I or II Atrioventricular synchrony (paced or intrinsic) Exclusion Criteria: Tetrology of Fallot, total or partial anomalous venous connection More than trivial MS or outflow obstruction Other sources of LV volume overload Hypertrophic obstructive cardiomyopathy Significant residual coarctation

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br> | Other: Placebo<br>* Placebo An inert preparation with similar appearance and taste to the drug<br>|
| Active Comparator: 2<br>Ace inhibition (enalapril) | Drug: Enalapril<br>* Up-titration period is to reach the highest tolerated dose up to a maximum of 0.4 mg/kg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the effect of ACE-I therapy with that of placebo on left ventricular size |  | Measured after six months of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the effect of ACE-I therapy with placebo on MR severity, left ventricular geometry, hemodynamics, and signs and symptoms of congestive heart failure |  | 6 months on study drug | 
| Evaluation of the early natural history of MR in the six months after repair of an AVSD |  | 6 months on study drug | 
| Comparison of the incidence of adverse events occurring in subjects treated with ACE-I therapy to that in subjects receiving placebo (measured after six months of therapy) |  | 6 months on safety drug |