Infant Single Ventricle (ISV)

(Enalapril vs Placebo Trial)

Study Summary

Infant Single Ventricle – ISV was a trial testing a medication in infants after surgery for single ventricle.

This study was done to see if giving a medication called Enalapril (an ACE inhibitor) would improve a baby’s growth and heart function in the first year of life. The study began on August 25, 2003 and the last infant was enrolled in May 2007 with 230 babies enrolled.

5 Years of Enrollment

The study began on August 25, 2003 and the last infant was enrolled in May 2007

230 Babies

Were enrolled in this study

No Benefit

Enalapril did not provide a benefit for a baby’s growth, heart function, or development at 14 months of age

Who was in the study?

Children with a single ventricle (lower pumping chamber) heart instead of 2 ventricles were in the study if they:
  • Were less than 45 days of age and stable
  • Were born no earlier than 35 weeks and weigh at least 2.5 Kg at birth (about 5½ pounds)
  • Planned to have a Glenn shunt surgery
  • Had not been on an ACE inhibitor for more than 7 days

What happened during the study?

Each qualified child was randomly assigned to one of two treatment groups. One group received Enalapril and the other group received a placebo. Babies were followed until they reached 14 months of age.

During the study period, the following data was collected:
  • Blood tests periodically to make sure that the medicine was well tolerated.
  • Echocardiograms prior to starting the study, prior to the Glenn surgery and again at 14 months of age.
  • Height and weight was checked prior to starting the drug, at 14 days, prior to the Glenn surgery and again at 14 months.
  • Neurodevelopmental examination was done at 14 months of age.

What were the results of the study?

The ACE inhibitor medication called Enalapril did not provide a benefit for a baby’s growth, heart function, or development at 14 months of age.

What we learned may or may not apply to a specific child. These findings are based on all 230 children, and individual results may be different.

The PHN is grateful to all of the families who participated in this study. The results from this study has helped us to learn more about improving the care of children with a single ventricle heart defect. The Pediatric Heart Network plans to use these results to design additional studies in the near future.

Study Publications

  • Enalapril in Infants with Single Ventricle: results of a multicenter randomized trial

    D. Hsu, Circulation 2010; 122:333-340.

    Read Publication

  • Rationale and Design of a Trial of Angiotensin-Converting Enzyme Inhibition in Infants With Single Ventricle

    D. Hsu, Am Heart J 2009; 157:37-45.

    Angiotensin-converting enzyme (ACE) inhibitors are medicines that improve heart function in adults with heart failure. Infants with a particular type of congenital heart defect (known as single ventricle) have been shown to have abnormal heart function and poor growth. This study was designed to determine if giving ACE inhibitors to babies with single-ventricles would improve their growth, heart function and development. This article describes the design, the participants and the procedures of this trial.

    Read Publication

  • Birth Weight and Prematurity in Infants With Single Ventricle Physiology: Pediatric Heart Network Infant Single Ventricle Trial Screened Population

    R. Williams, Congenit Heart Dis 2010; 5:96-103.

    Many congenital heart defects are associated with low birth weight and prematurity, but there is little information on birth characteristics of babies with a specific kind of defect, single ventricle physiology. This study compares birth parameters for babies enrolled in the Infant Single Ventricle Trial as compared to the typical US population. Infants with single ventricle had increased rates of preterm birth and low birth weight, and they were more likely to be small for gestational age than the general population.

    Read Publication

  • Renin-Angiotensin-Aldosterone Genotype Influences Ventricular Remodeling in Infants with Single Ventricle

    S. Mital, Circulation 2011; 123:2353-2362.

    Read Publication

  • Factors Impacting Growth in Infants with Single Ventricle Physiology: A Report from Pediatric Heart Network Infant Single Ventricle Trial

    R. Williams, J Pediatr 2011; 159:1017-22.

    Read Publication

  • Challenges and successes of recruitment in the “angiotensin-converting enzyme inhibition in infants with single ventricle trial” of the Pediatric Heart Network

    N. Pike, Cardiol Young 2013; 23(2): 248–257.

    Read Publication

  • Association of impaired linear growth and worse neurodevelopmental outcome in infants with single ventricle physiology: A report from the Pediatric Heart Network Infant Single Ventricle Trial

    C. Ravishankar, J Pediatr 2013; 162(2): 250–256.e2.

    Read Publication

  • Superior cavopulmonary anastomosis timing and outcomes in infants with single ventricle

    J. Cnota, J Thorac Cardiovasc Surg 2013; 145(5): 1288–1296.

    Read Publication

  • The association of fetal cerebrovascular resistance with early neurodevelopment in single ventricle congenital heart disease

    I. Williams, Am Heart J 2013; 165(4):544-550.e1.

    Read Publication

  • The Impact of CNVs on Outcomes for Infants with Single Ventricle Heart Defects

    A. S. Carey, Circ Cardiovasc Genet. 2013 Oct; 6(5): 444–451.

    Read Publication

  • Factors Associated with Serum B- type Natriuretic Peptide Levels in Infants with Single Ventricle

    R. Butts, Pediatr Cardiol 2014; 35(5):879-87.

    Read Publication

  • Validation of association of the apolipoprotein E ε2 allele with neurodevelopmental dysfunction after cardiac surgery in neonates and infants

    J. W. Gaynor, J Thorac Cardiovasc Surg. 2014 Dec;148(6):2560-6.

    Read Publication

  • Neurodevelopmental outcomes after cardiac surgery in infancy

    J. Gaynor, Pediatrics 2015; 135(5):816-25.

    Read Publication

  • Growth Asymmetry, Head Circumference, and Neurodevelopmental Outcomes in Infants with Single Ventricles

    T. Miller, J Pediatr 2016; 168:220-225.

    Read Publication

  • The Effect of the Superior Cavopulmonary Anastomosis on Ventricular Remodeling in Infants with Single Ventricle

    R. Margossian, J Am Soc Echocardiogr 2017; 130(7):699-707.e1.

    Read Publication

  • Translating clinical trials into clinical practice: a survey assessing the potential impact of the Pediatric Heart Network Infant Single Ventricle Trial

    V. Zak, Cardiol Young 2017; 27(7):1265-1270.

    Read Publication