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

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

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: November 2005

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.

Intervention(s) in this Clinical Trial

• Drug: Enalapril
  • Up-titration period is to reach the highest tolerated dose up to a maximum of 0.4 mg/kg/day
• Other: Placebo
  • Placebo

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: 1
• Active Comparator: 2
  • Ace inhibition (enalapril)

Primary Measures

• Comparison of the effect of ACE-I therapy with that of placebo on left ventricular size
  • Time Frame: Measured after six months of therapy
    Safety Issue?: Yes

Secondary Measures

• 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
  • Time Frame: 6 months on study drug
    Safety Issue?: Yes
• Evaluation of the early natural history of MR in the six months after repair of an AVSD
  • Time Frame: 6 months on study drug
    Safety Issue?: Yes
• 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)
  • Time Frame: 6 months on safety drug
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 18 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Overall Clinical Trial Officials and Contacts

LuAnn Minich, MD Principal Investigator Primary Children's Hospital, Salt Lake City, UT  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00113698

Study ID Number: 185

ClinicalTrials.gov Identifier: NCT00113698

Health Authority: United States: Food and Drug Administration