Purpose

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.


Condition Intervention Phase
Heart Defects, Congenital
Heart Failure, Congestive
Drug: Enalapril
Drug: Placebo
Phase III

Genetics Home Reference related topics:   Congenital Heart Defects  

MedlinePlus related topics:   Congenital Heart Defects   Heart Failure  

ChemIDplus related topics:   Enalapril   Enalapril maleate   Enalaprilat  

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study
Official Title:   Trial of ACE Inhibition in Infants With Single Ventricle (A Trial Conducted by the Pediatric Heart Network)

Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome 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 ] [ Designated as safety issue: No ]
  • Echo endpoints [ Time Frame: Measured at baseline, just prior to the Glenn surgery, and at 14 months of age ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Brain natriuretic peptide and heart failure class [ Time Frame: Measured just prior to the Glenn surgery and at 14 months of age ] [ Designated as safety issue: No ]
  • Neurodevelopmental status [ Time Frame: Measured using three different assessments, including the Bayley Scales of Infant Development at 14 months of age ] [ Designated as safety issue: No ]

Enrollment:   230
Study Start Date:   August 2003
Estimated Study Completion Date:   September 2009
Estimated Primary Completion Date:   September 2009 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
1: Active Comparator
Enalapril
Drug: Enalapril
Enalapril to target dose of .4mg/kg/day divided to twice per day (BID)
2: Placebo Comparator
Placebo Enalapril
Drug: Placebo
Participants will receive placebo Enalapril

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.

  Eligibility
Ages Eligible for Study:   up to 45 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00113087

Locations
United States, Massachusetts
Children's Hospital Boston    
      Boston, Massachusetts, United States, 02115
United States, New York
Columbia College of Physicians and Surgeons    
      New York, New York, United States, 10032
United States, North Carolina
Duke University Medical Center    
      Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital Medical Center    
      Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia    
      Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Medical University of South Carolina    
      Charleston, South Carolina, United States, 29425
United States, Utah
Primary Children's Hospital    
      Salt Lake City, Utah, United States, 84113
United States, Wisconsin
Children's Hospital of Wisconsin    
      Milwaukee, Wisconsin, United States, 53226
Canada, Ontario
Hospital for Sick Children    
      Toronto, Ontario, Canada, M5G 1X8

Sponsors and Collaborators

Investigators
Principal Investigator:     Page Anderson, MD     Duke University Medical Center, Durham, NC    
Principal Investigator:     Daphne Hsu, MD     The Children's Hospital at Montefiore, NYC, NY    
Principal Investigator:     Brian McCrindle, MD     Hospital for Sick Children, Toronto, Canada    
Principal Investigator:     LuAnn Minich, MD     Primary Children's Hospital, Salt Lake City, UT    
Principal Investigator:     Jane Newburger, MD     Children's Hospital Boston, Boston, MA    
Principal Investigator:     J. Philip Saul, MD     Medical University of South Carolina, Charleston, SC    
Principal Investigator:     Lynn Sleeper, Sc.D.     New England Research Institute, Watertown, MA    
Principal Investigator:     Victoria Vetter, MD     Children's Hospital of Philadelphia, Philadelphia, PA    
Principal Investigator:     Woodrow Benson, MD     Cincinnati Children's Medical Center, Cincinnati, OH    
United States, Massachusetts
Children's Hospital Boston    
      Boston, Massachusetts, United States, 02115
United States, New York
Columbia College of Physicians and Surgeons    
      New York, New York, United States, 10032
United States, North Carolina
Duke University Medical Center    
      Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Hospital Medical Center    
      Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Children's Hospital of Philadelphia    
      Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Medical University of South Carolina    
      Charleston, South Carolina, United States, 29425
United States, Utah
Primary Children's Hospital    
      Salt Lake City, Utah, United States, 84113
United States, Wisconsin
Children's Hospital of Wisconsin    
      Milwaukee, Wisconsin, United States, 53226
Canada, Ontario
Hospital for Sick Children    
      Toronto, Ontario, Canada, M5G 1X8
National Heart, Lung, and Blood Institute (NHLBI)
Pediatric Heart Network
Principal Investigator:     Page Anderson, MD     Duke University Medical Center, Durham, NC    
Principal Investigator:     Daphne Hsu, MD     The Children's Hospital at Montefiore, NYC, NY    
Principal Investigator:     Brian McCrindle, MD     Hospital for Sick Children, Toronto, Canada    
Principal Investigator:     LuAnn Minich, MD     Primary Children's Hospital, Salt Lake City, UT    
Principal Investigator:     Jane Newburger, MD     Children's Hospital Boston, Boston, MA    
Principal Investigator:     J. Philip Saul, MD     Medical University of South Carolina, Charleston, SC    
Principal Investigator:     Lynn Sleeper, Sc.D.     New England Research Institute, Watertown, MA    
Principal Investigator:     Victoria Vetter, MD     Children's Hospital of Philadelphia, Philadelphia, PA    
Principal Investigator:     Woodrow Benson, MD     Cincinnati Children's Medical Center, Cincinnati, OH    
  More Information

Responsible Party:   New England Research Institutes ( Lynn Sleeper, PI )
Study ID Numbers:   177, U01 HL068270, U01 HL068279, U01 HL068281, U01 HL068285, U01 HL068288, U01 HL068290, U01 HL068292, U07 HL068269
First Received:   June 3, 2005
Last Updated:   June 30, 2008
ClinicalTrials.gov Identifier:   NCT00113087
Health Authority:   United States: Food and Drug Administration

Study placed in the following topic categories:
Enalapril
Heart Failure
Heart Diseases
Enalaprilat
Cardiovascular Abnormalities
Single ventricular heart
Heart Defects, Congenital

Additional relevant MeSH terms:
Heart Defects, Congenital
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Angiotensin-Converting Enzyme Inhibitors
Enzyme Inhibitors
Cardiovascular Diseases
Cardiovascular Agents
Antihypertensive Agents
Congenital Abnormalities
Pharmacologic Actions
Protease Inhibitors

Source: National Library of Medicine (NLM) July 03, 2008