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Phase 3 N=230 Randomized Triple-blind Treatment

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

Heart Defects, Congenital · Heart Failure, Congestive

Enrolled (actual)
230
Serious AEs
76.1%
Results posted
Sep 2010
Primary outcome: Primary: Weight-for-age Z-score at 14 Months of Age — -0.62; -0.42 standard deviation — p=0.28

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Enalapril (Drug); Placebo (Drug)
Age
Pediatric
Sex
All
Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
Primary completion
Jul 2008

Outcome Measures

OutcomeResultp-value
PRIMARY
Weight-for-age Z-score at 14 Months of Age
-0.62; -0.42 0.28
SECONDARY
Height-for-age Z-score
-1.00; -0.86 0.42
SECONDARY
Head Circumference-for-age Z-score
-0.55; 0.09 0.008 sig
SECONDARY
Number of Participants With Ross Heart Failure Class I
72; 77 0.71
SECONDARY
Number of Participants With Ross Heart Failure Class I
72; 77 0.71
SECONDARY
B-Type Natriuretic Peptide
79; 84 0.74
SECONDARY
B-type Natriuretic Peptide Level
25; 39 0.22
SECONDARY
Neurodevelopmental Status (PDI): the Bayley Scales of Infant Development,Psychomotor Development Index Z-score
-1.29; -1.32 0.86
SECONDARY
Neurodevelopmental Status(MDI): Bayley Scales of Infant Development, Mental Developmental Index Z-score
-0.26; -0.33 0.60
SECONDARY
Neurodevelopmental Status (FSII)
96.4; 96.4 0.60
SECONDARY
MacArthur-Bates Inventory -Phrases Understood
-0.48; -0.92 0.01 sig
SECONDARY
MacArthur-Bates Inventory -Words Understood
-0.46; -0.82 0.008 sig
SECONDARY
MacArthur-Bates Inventory -Total Gestures
-0.86; -1.31 0.004 sig
SECONDARY
MacArthur-Bates Inventory -Words Produced
-0.60; -0.63 0.31
SECONDARY
Ejection Fraction (%)
59.3; 57.9 0.37
SECONDARY
Ejection Fraction (%)
59.3; 57.9 0.37
SECONDARY
Ventricular Mass
31.4; 34.4 0.07
SECONDARY
Ventricular Mass
31.4; 34.4 0.07
SECONDARY
Ventricular Mass Z-score
2.5; 3.1 0.11
SECONDARY
Ventricular Mass Z-score
2.5; 3.1 0.11
SECONDARY
End-diastolic Volume
29.2; 30.7 0.35
SECONDARY
End-diastolic Volume
29.2; 30.7 0.35
SECONDARY
End Diastolic Volume Z-score
2.3; 2.1 0.62
SECONDARY
End-diastolic Volume Z-score
1.1; 1.3 0.43
SECONDARY
Ventricular Mass to Volume Ratio
1.14; 1.20 0.34
SECONDARY
Ventricular Mass to Volume Ratio
1.14; 1.20 0.34
SECONDARY
Ventricular Filling Pressure
10.9; 11.1 .81
SECONDARY
Number of Participants With Moderate to Severe AV Valve Regurgitation
11; 22 0.06
SECONDARY
Number of Participants With Moderate to Severe AV Valve Regurgitation
11; 22 0.06

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.

Eligibility 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
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00113087). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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