Trial of Angiotensin Converting Enzyme Inhibition in Infants With Single Ventricle--Pediatric Heart Network
- Conditions
- Heart Defects, CongenitalHeart Failure, Congestive
- Interventions
- Drug: Placebo
- Registration Number
- NCT00113087
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 230
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo (Ora-Plus and Ora-Sweet) Enalapril Enalapril Enalapril (angiotensin converting enzyme inhibitor)
- Primary Outcome Measures
Name Time Method Weight-for-age Z-score at 14 Months of Age 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 Weight-for-age z-score at 14 months of age. In primary analysis outcome is defined as predicted mean of weight z-score at age 14 months based on longitudinal modeling(and adjusted for baseline values)
- Secondary Outcome Measures
Name Time Method Height-for-age Z-score 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 Height-for-age z-score at 14 months of age. In primary analysis outcome is defined as predicted mean of height z-score at age 14 months based on longitudinal modeling (adjusted bor baseline value)
MacArthur-Bates Inventory -Phrases Understood at 14 months of age MacArthur-Bates Communicative Development inventory( Words and Gestures)-Phrases Understood z-score.
MacArthur-Bates Inventory -Words Understood at 14 months of age MacArthur-Bates Communicative Development inventory( Words and Gestures)-Words Understood z-score.
B-Type Natriuretic Peptide Measured just prior to the Glenn surgery B-Type Natriuretic Peptide (BNP) level.
Number of Participants With Ross Heart Failure Class I Measured at 14 months of age Class I is defined as having no limitations or symptoms of heart failure. Classes II to IV include increasing degrees of growth failure, prolonged feeding time, tachypnea, diaphoresis, and in older children, dyspnea on exercise.
B-type Natriuretic Peptide Level at the time of the 14 month visit B-type natriuretic peptide (BNP) level.
Head Circumference-for-age Z-score 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 Head circumference-for-age z-score at 14 months of age.In primary analysis outcome is defined as predicted mean of Head circumference z-score at age 14 months based on longitudinal modeling(and adjusted for baseline values)
Neurodevelopmental Status (PDI): the Bayley Scales of Infant Development,Psychomotor Development Index Z-score at 14 months of age Neurodevelopmental status (PDI):
the Bayley Scales of Infant Development: Psychomotor Development index z-score .Neurodevelopmental Status(MDI): Bayley Scales of Infant Development, Mental Developmental Index Z-score at 14 months of age Neurodevelopmental status(MDI):Bayley Scales of infant development, Mental Developmental Index z-score .
Neurodevelopmental Status (FSII) at 14 months of age Functional status II (Revised) Total Score. Scale ranges up to 100.00, the higher the better. The score presents an instrument for assessing health status for children surviving long term with chronic physcial disorders.
MacArthur-Bates Inventory -Total Gestures at 14 months of age MacArthur-Bates Communicative Development inventory( Words and Gestures)-Total Gestures z-score.
MacArthur-Bates Inventory -Words Produced at 14 months of age MacArthur-Bates Communicative Development inventory( Words and Gestures)-Words Produced z-score.
Ejection Fraction (%) at 14 months of age Two-dimensional echocardiography endpoint -Total Ejection Fraction (%) per Core Laboratory assessment. Ejection Fraction (%) is defined as percentage of stroke volume of a ventricle (i.e. the difference between end diastolic and end systolic volumes)relative to end diastolic volume.
Ventricular Mass At 14 months of age Two-Dimensional Echocardiography endpoint-Total Ventricular mass (g) per Core Laboratory assessment. Range from 15.60 to 70.40
Ventricular Mass Z-score at 14 months of age Two-dimensional echocardiography endpoint -Total Ventricular mass z-score per Core Laboratory assessment.
End-diastolic Volume at 14 months of age Two-Dimensional Echocardiography endpoint - Total End-diastolic volume (ml) per Core Laboratory assessment.
End Diastolic Volume Z-score just before the Glenn surgery Two-dimensional echocardiography endpoint -total End diastolic volume z-score per Core Laboratory assessment.
Ventricular Mass to Volume Ratio Measured at 14 months of age Two-Dimensional Echocardiography endpoint -Ventricular Mass to Volume ratio per Core Laboratory assessment.
End-diastolic Volume Z-score at 14 months of age Two-dimensional echocardiography endpoint -total end-diastolic volume z-score per Core Laboratory assessment.
Ventricular Filling Pressure just before the Glenn surgery Ventricular filling pressure measured by catherization
Number of Participants With Moderate to Severe AV Valve Regurgitation at age 14 months Number of participants with moderate to severe AV valve regurgitation.
Trial Locations
- Locations (9)
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Children's Hospital Boston
🇺🇸Boston, Massachusetts, United States
Columbia College of Physicians and Surgeons
🇺🇸New York, New York, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States