Clinical trial NCT00113698: Angiotensin Converting Enzyme Inhibition in Children With Mitral Regurgitation
Official title: Trial of ACE Inhibition in Children With Mitral Regurgitation After Repair of AVSD
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Heart Defects, Congenital
Heart Septal Defects, Ventricular
Heart Failure, Congestive
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Pediatric Heart Network
First posted: 2005-06-10
Enrollment: 5
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Comparison of the effect of ACE-I therapy with that of placebo on left ventricular size
timeFrame: Measured after six months of therapy
Secondary outcomes:
measure: 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
timeFrame: 6 months on study drug
measure: Evaluation of the early natural history of MR in the six months after repair of an AVSD
timeFrame: 6 months on study drug
measure: 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)
timeFrame: 6 months on safety drug
Other outcomes:
Locations:
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: New York
country: United States
facility: Columbia College of Physicians and Surgeons
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Primary Children's Hospital, Salt Lake City, UT
name: LuAnn Minich, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Li JS, Colan SD, Sleeper LA, Newburger JW, Pemberton VL, Atz AM, Cohen MS, Golding F, Klein GL, Lacro RV, Radojewski E, Richmond ME, Minich LL. Lessons learned from a pediatric clinical trial: the Pediatric Heart Network angiotensin-converting enzyme inhibition in mitral regurgitation study. Am Heart J. 2011 Feb;161(2):233-40. doi: 10.1016/j.ahj.2010.10.030.
citation: Atz AM, Hawkins JA, Lu M, Cohen MS, Colan SD, Jaggers J, Lacro RV, McCrindle BW, Margossian R, Mosca RS, Sleeper LA, Minich LL; Pediatric Heart Network Investigators. Surgical management of complete atrioventricular septal defect: associations with surgical technique, age, and trisomy 21. J Thorac Cardiovasc Surg. 2011 Jun;141(6):1371-9. doi: 10.1016/j.jtcvs.2010.08.093. Epub 2010 Dec 15.