Trial of Angiotensin Converting Enzyme Inhibition in Infants With Single Ventricle--Pediatric Heart Network

Condition(s) targeted: Heart Defects, Congenital; Heart Failure, Congestive

Intervention: Enalapril (Drug); Placebo (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)

Official(s) and/or principal investigator(s):
Page Anderson, MD, Principal Investigator, Affiliation: Duke University Medical Center, Durham, NC
Daphne Hsu, MD, Principal Investigator, Affiliation: The Children's Hospital at Montefiore, NYC, NY
Brian McCrindle, MD, Principal Investigator, Affiliation: Hospital for Sick Children, Toronto, Canada
LuAnn Minich, MD, Principal Investigator, Affiliation: Primary Children's Hospital, Salt Lake City, UT
Jane Newburger, MD, Principal Investigator, Affiliation: Children's Hospital Boston, Boston, MA
J. Philip Saul, MD, Principal Investigator, Affiliation: Medical University of South Carolina, Charleston, SC
Lynn Sleeper, Sc.D., Principal Investigator, Affiliation: New England Research Institute, Watertown, MA
Victoria Vetter, MD, Principal Investigator, Affiliation: Children's Hospital of Philadelphia, Philadelphia, PA
Woodrow Benson, MD, Principal Investigator, Affiliation: Cincinnati Children's Medical Center, Cincinnati, OH

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.

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

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

Primary outcome:

Growth

Echo endpoints

Secondary outcome:

Brain natriuretic peptide and heart failure class

Neurodevelopmental status

Detailed description: 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.

Minimum age: N/A. Maximum age: 45 Days. Gender(s): Both.

Criteria:

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

Children's Hospital Boston, Boston, Massachusetts 02115, United States

Columbia College of Physicians and Surgeons, New York, New York 10032, United States

Duke University Medical Center, Durham, North Carolina 27710, United States

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, United States

Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States

Medical University of South Carolina, Charleston, South Carolina 29425, United States

Primary Children's Hospital, Salt Lake City, Utah 84113, United States

Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53226, United States

Starting date: August 2003
Ending date: October 2009
Last updated: February 7, 2008