To evaluate novel treatment methods and management strategies for children with structural congenital heart disease, inflammatory heart disease, heart muscle diseases, and arrhythmia.

Condition	Treatment or Intervention
Kawasaki Disease (KD) Pediatric Heart Disease Heart Failure Defect, Congenital Heart	Drug: see design narrative for drug details  Device: Biventricular pacing

Further Study Details: 

BACKGROUND: Approximately 32,000 infants are born each year in the United States with congenital cardiovascular malformations, the most common congenital anomaly, and one of the leading causes of infant mortality. A significant number of additional children experience medical problems from inflammatory cardiac conditions, heart muscle disease, and arrhythmias. Affected children experience morbidity and mortality that generate health and economic consequences out of proportion to their numbers. In spite of recent improvement, the mortality rate for structural congenital malformations varies from less than 1 percent to as high as 50 percent, depending on the condition. The medical, social and economic consequences of pediatric heart disease are profound, and include frequent medical monitoring and the need for invasive procedures, high medical care expenses, disruption of family life, the high cost of potential productive years of life lost when a child dies, and loss of parental productivity and wages.

Treatment of congenital and acquired pediatric heart disease involves medical, surgical, and catheter-based approaches. Few drugs used as "standard therapy" have been tested in randomized controlled trials in pediatrics. For example, standard pharmacological agents used in the treatment of adult heart failure, such as diuretics, digitalis, angiotensin-converting enzyme (ACE) inhibitors, and beta-blockers, are used in children, but have not been studied in a systematic fashion.

The optimal timing and approach for complex congenital structural malformations including the several malformations that lead to single ventricle physiology are not known, and the risks and benefits of devices compared to surgical repair of certain defects have not been studied systematically. In addition, the acute and chronic post-operative course can be complicated by conditions such as post-cardiopulmonary bypass syndrome (especially in infants), arrhythmias including those implicated in sudden death, neurodevelopmental deficits, ventricular dysfunction and heart failure, and coagulapthy leading to the need for reoperation. Treatment strategies for these conditions are not supported by systematic prospective clinical studies.

The network approach is an effective, flexible way to study adequate numbers of patients with uncommon diseases, such as congenital cardiovascular malformations. The collaborative effort through a clinical research network is the most scientifically sound and cost-effective way to overcome the current barriers and provide the information needed to bring evidence-based medicine to bear on children with heart disease.

The Request for Applications was issued in May, 2000.

DESIGN NARRATIVE: The network has established the infrastructure for a data coordinating center and seven clinical centers to recruit, monitor and follow patients whose conditions are characterized in a standard fashion. The network also serves as a platform to train junior investigators in pediatric clinical research and as a vehicle to rapidly disseminate scientific findings.

Trial of Pulse Steroid Therapy for Kawasaki Disease Kawasaki Disease (KD) is an inflammatory vasculitis of unknown etiology that affects infants and children and can cause coronary artery aneurysms. Standard therapy consists of 2 gm/kg of intravenous immune globulin plus high-dose aspirin in the acute phase, and low-dose aspirin in the convalescent phase. Some children do not respond to this therapy, and some children go on to develop coronary artery aneurysms in spite of aggressive treatment. This led to the design of this randomized controlled trial to compare a single dose of intravenous steroids vs. placebo on the background of standard therapy. The primary endpoint is coronary artery diameter, normalized for body surface area, 5 weeks after randomization. Secondary endpoints include duration of fever, CRP levels, and adverse events. Recruitment began in December, 2002 and ended in December, 2004 with nearly 200 patients randomized.

Angiotensin-converting enzyme (ACE) Inhibition in the Treatment of Mitral Valve Regurgitation After Repair of Complete Atrioventricular Canal Defects This study seeks to evaluate the efficacy and safety of enalapril therapy initiated 6-18 months after repair of atrioventricular septal defect in children (less than 5 years of age) who have at least moderate mitral regurgitation. Echocardiographic measurements have been standardized across all participating centers to assess left ventricular geometry and hemodynamic outcomes.

ACE Inhibition in Infants with Single Ventricle The purpose of this trial is to determine the effect of ACE inhibition (enalapril) on somatic growth in infants with single ventricle physiology who have undergone the first staged surgical procedure. Secondary endpoints include signs and symptoms of congestive heart failure, developmental indices, and electrocadiographic and MRI measures of ventricular mass, volume, and function in the subjects in the two groups. Recruitment began in August, 2003 with a target of 216.

The Relationship Between Functional Health Status and Laboratory Parameters of Ventricular Performance After the Fontan Procedure study has completed recruitment with the enrollment of 546 patients. The purpose of this cross-sectional study was to determine the interrelationships between health status and measures of cardiac performance in children 6 to 18 years of age with congenital heart disease who have undergone a Fontan procedure as surgical treatment for functional single ventricle. The goal was to develop a data set that will permit identification of a clinically relevant endpoint for subsequent trials of medical management of the Fontan patient.

Single Ventricle Reconstruction Trial The standard surgical approach for neonates with single ventricle physiology will be compared to a novel surgical procedure. The trial was developed in concert with two non-network centers which will participate in study management and recruitment.

Venticular Volume Variability Trial This is a study of variability in echocardiographic measures of ventricular performance. Variability will be assessed within patients as disease changes, across time, and between echocardiographics to help refine the confidence intervals around measurements that may be used in the future as trial endpoints.

Ages Eligible for Study:  up to  21 Years,  Genders Eligible for Study:  Both

Criteria

Varies with protocol

Massachusetts
      Children's Hospital of Boston, Boston,  Massachusetts,  02115,  United States; Recruiting
New York
      Columbia Presbyterian Medical Center, New York,  New York,  10024,  United States; Recruiting
North Carolina
      Duke University Medical Center, Durham,  North Carolina,  United States; Recruiting
Pennsylvania
      Children's Hospital of Philadelphia, Philadelphia,  Pennsylvania,  191104-439,  United States; Recruiting
South Carolina
      Medical University of South Carolina, Charleston,  South Carolina,  29425,  United States; Recruiting
Utah
      Primary Children's Medical Center, Salt Lake City,  Utah,  84113,  United States; Recruiting
Canada, Ontario
      Hospital for Sick Children, Toronto,  Ontario,  M5G 1X8,  Canada; Recruiting

Study chairs or principal investigators

Page Anderson,  Duke University   
Welton Gersony,  Columbia Presbyterian Medical Center   
Brian McCrindle,  The Hospital for Sick Children   
LuAnn Minich,  Primary Children's Medical Center   
Jane Newburger,  Children's Hospital Boston   
J. Saul,  Medical University of South Carolina   
Lynn Sleeper,  New England Research Institute Inc.   
Victoria Vetter,  Children's Hospital of Philadelphia   

Study ID Numbers:  138
Record last reviewed:  March 2005
Last Updated:  March 18, 2005
Record first received:  September 7, 2001
ClinicalTrials.gov Identifier:  NCT00023517
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08