Official Title: “Trial of ACE Inhibition in Infants With Single Ventricle (A Trial Conducted by the Pediatric Heart Network)”

This study will evaluate the efficacy and safety of administering an angiotensin converting enzyme inhibitor (ACE-I) (enalapril) to infants with a functional single ventricle. The study will also compare the effect of ACE-I therapy to placebo on somatic growth and compare the effect of ACE-I therapy to placebo on signs and symptoms of heart failure, neurodevelopmental and functional status, ventricular geometry, function, and atrioventricular (AV) valve regurgitation. In addition, the study will determine the relationship between genetic polymorphisms linked to ventricular hypertrophy (enlarged heart) and the response to ACE-I therapy and compare the incidence of adverse events in subjects treated with ACE-I with those in subjects treated with placebo.

Study Type: Interventional

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

Study Primary Completion Date: September 2009

BACKGROUND:

Growth impairment is common in infants and children with congenital heart disease, most often in the presence of congestive heart failure and/or cyanosis. Growth failure is noted in many infants with a single ventricle who manifest both cyanosis and heart failure that commonly persist after palliative surgery. Whether this impairment is related to persistent or progressive abnormalities in cardiac structure and function is not known. ACE-Is are widely used in the treatment of infants with severe congestive heart failure to improve cardiac function and somatic growth. The ability of an ACE-I to improve somatic growth in infants with a single ventricle has not been previously studied.

This study has been approved by the Institutional Review Boards/Research Ethics Boards of all participating clinical centers:

Hospital for Sick Children, Toronto, Canada

Children's Hospital Boston, Boston, MA

Columbia College of Physicians and Surgeons, New York, NY

Children's Hospital of Philadelphia, Philadelphia, PA

Duke University Medical Center, Durham, NC

Brody School of Medicine at East Carolina University, Greenville, NC

Wake Forest Baptist Medical Center, Winston Salem, NC

Medical University of South Carolina, Charleston, SC

Primary Children's Medical Center, Salt Lake City, UT

Children's Hospital of Wisconsin, Milwaukee, WI

Cincinnati Children's Hospital Medical Center, Cincinnati, OH

DESIGN NARRATIVE:

This is a prospective, randomized, double-blind, placebo-controlled trial of ACE-I in infants with a single ventricle. After stratification by ventricular anatomy, neonates will be randomly assigned to receive enalapril or placebo and then followed for 14 months.

Intervention(s) in this Clinical Trial

• Drug: Enalapril
  • Enalapril to target dose of .4mg/kg/day divided to twice per day (BID)
• Drug: Placebo
  • Participants will receive placebo Enalapril

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Enalapril
• Placebo Comparator: 2
  • Placebo Enalapril

Primary Measures

• Growth
  • Time Frame: Measured at baseline, 2 weeks after starting study drug, just prior to the Glenn surgery, 7 days after restarting drug following the Glenn surgery, at 10 months of age, and at 14 months of age
    Safety Issue?: No
• Echo endpoints
  • Time Frame: Measured at baseline, just prior to the Glenn surgery, and at 14 months of age
    Safety Issue?: No

Secondary Measures

• Brain natriuretic peptide and heart failure class
  • Time Frame: Measured just prior to the Glenn surgery and at 14 months of age
    Safety Issue?: No
• Neurodevelopmental status
  • Time Frame: Measured using three different assessments, including the Bayley Scales of Infant Development at 14 months of age
    Safety Issue?: No

Inclusion Criteria:

• Less than or equal to 45 days of age
• Age greater than 1 week if born at 35 weeks gestation
• Single ventricle physiology
• Stable systemic and pulmonary blood flow
• Planned Glenn shunt surgery (or variant known as hemi-Fontan)

Exclusion Criteria:

• Birth weight less than or equal to 2.5 kg if gestational age is greater than or equal to 38 weeks
• Birth weight less than the 10th percentile for gestational age if gestational age is 35 to 37 weeks
• Less than 35 weeks gestation
• Anatomic diagnosis of pulmonary atresia with intact ventricular septum
• Less than 3 days after palliative cardiac surgical procedure, if performed
• Aortic oxygen saturation less than 65%
• Current mechanical ventilatory support
• Current intravenous inotropic support
• Creatinine greater than 1.0 mg/dL
• Absolute neutrophil count less than 1,000 cells/mL
• Chromosomal or recognizable phenotypic syndrome of noncardiac congenital abnormalities associated with growth failure (e.g., Trisomy 21, Noonan's syndrome, Turner's syndrome)
• Prior ACE inhibitor use for greater than 7 consecutive days

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 45 Days

Are Healthy Volunteers Accepted for this Clinical Trial?: No

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

Overall Clinical Trial Officials and Contacts

Page Anderson, MD Principal Investigator Duke University Medical Center, Durham, NC  

Information obtained from ClinicalTrials.gov on October 07, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00113087

Study ID Number: 177

ClinicalTrials.gov Identifier: NCT00113087

Health Authority: United States: Food and Drug Administration