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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
230

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Aug 2003

Longer than P75 for phase_3

Geographic Reach
2 countries

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2003

Completed
1.8 years until next milestone

First Submitted

Initial submission to the registry

June 3, 2005

Completed
3 days until next milestone

First Posted

Study publicly available on registry

June 6, 2005

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2008

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2008

Completed
2.2 years until next milestone

Results Posted

Study results publicly available

September 16, 2010

Completed
Last Updated

September 28, 2010

Status Verified

September 1, 2009

Enrollment Period

4.9 years

First QC Date

June 3, 2005

Results QC Date

September 4, 2009

Last Update Submit

September 16, 2010

Conditions

Heart Defects, CongenitalHeart Failure, Congestive

Outcome Measures

Primary Outcomes (1)

  • Weight-for-age Z-score 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)

    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

Secondary Outcomes (28)

  • 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

  • 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

  • Number of Participants With Ross Heart Failure Class I

    Just prior to the pre-Glenn surgery

  • Number of Participants With Ross Heart Failure Class I

    Measured at 14 months of age

  • B-Type Natriuretic Peptide

    Measured just prior to the Glenn surgery

  • +23 more secondary outcomes

Study Arms (2)

Enalapril

ACTIVE COMPARATOR

Enalapril (angiotensin converting enzyme inhibitor)

Drug: Enalapril

Placebo

PLACEBO COMPARATOR

Placebo (Ora-Plus and Ora-Sweet)

Drug: Placebo

Interventions

EnalaprilDRUG

Enalapril to target dose of .4mg/kg/day divided to twice per day (BID)

Enalapril
PlaceboDRUG

Participants will receive placebo

Placebo

Eligibility Criteria

AgeUp to 45 Days
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Columbia College of Physicians and Surgeons

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (8)

  • Miller TA, Zak V, Shrader P, Ravishankar C, Pemberton VL, Newburger JW, Shillingford AJ, Dagincourt N, Cnota JF, Lambert LM, Sananes R, Richmond ME, Hsu DT, Miller SG, Zyblewski SC, Williams RV; Pediatric Heart Network Investigators. Growth Asymmetry, Head Circumference, and Neurodevelopmental Outcomes in Infants with Single Ventricles. J Pediatr. 2016 Jan;168:220-225.e1. doi: 10.1016/j.jpeds.2015.09.041. Epub 2015 Oct 17.

    PMID: 26490132DERIVED

  • Ravishankar C, Zak V, Williams IA, Bellinger DC, Gaynor JW, Ghanayem NS, Krawczeski CD, Licht DJ, Mahony L, Newburger JW, Pemberton VL, Williams RV, Sananes R, Cook AL, Atz T, Khaikin S, Hsu DT; Pediatric Heart Network Investigators. 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. J Pediatr. 2013 Feb;162(2):250-6.e2. doi: 10.1016/j.jpeds.2012.07.048. Epub 2012 Aug 30.

    PMID: 22939929DERIVED

  • Cnota JF, Allen KR, Colan S, Covitz W, Graham EM, Hehir DA, Levine JC, Margossian R, McCrindle BW, Minich LL, Natarajan S, Richmond ME, Hsu DT; Pediatric Heart Network Investigators. Superior cavopulmonary anastomosis timing and outcomes in infants with single ventricle. J Thorac Cardiovasc Surg. 2013 May;145(5):1288-96. doi: 10.1016/j.jtcvs.2012.07.069. Epub 2012 Aug 28.

    PMID: 22939855DERIVED

  • Pike NA, Pemberton V, Allen K, Jacobs JP, Hsu DT, Lewis AB, Ghanayem N, Lambert L, Crawford K, Atz T, Korsin R, Xu M, Ravishankar C, Cnota J, Pearson GD. Challenges and successes of recruitment in the "angiotensin-converting enzyme inhibition in infants with single ventricle trial" of the Pediatric Heart Network. Cardiol Young. 2013 Apr;23(2):248-57. doi: 10.1017/S1047951112000832. Epub 2012 Jul 5.

    PMID: 22931751DERIVED

  • Williams RV, Zak V, Ravishankar C, Altmann K, Anderson J, Atz AM, Dunbar-Masterson C, Ghanayem N, Lambert L, Lurito K, Medoff-Cooper B, Margossian R, Pemberton VL, Russell J, Stylianou M, Hsu D; Pediatric Heart Network Investigators. Factors affecting growth in infants with single ventricle physiology: a report from the Pediatric Heart Network Infant Single Ventricle Trial. J Pediatr. 2011 Dec;159(6):1017-22.e2. doi: 10.1016/j.jpeds.2011.05.051. Epub 2011 Jul 23.

    PMID: 21784436DERIVED

  • Mital S, Chung WK, Colan SD, Sleeper LA, Manlhiot C, Arrington CB, Cnota JF, Graham EM, Mitchell ME, Goldmuntz E, Li JS, Levine JC, Lee TM, Margossian R, Hsu DT; Pediatric Heart Network Investigators. Renin-angiotensin-aldosterone genotype influences ventricular remodeling in infants with single ventricle. Circulation. 2011 May 31;123(21):2353-62. doi: 10.1161/CIRCULATIONAHA.110.004341. Epub 2011 May 16.

    PMID: 21576655DERIVED

  • Hsu DT, Zak V, Mahony L, Sleeper LA, Atz AM, Levine JC, Barker PC, Ravishankar C, McCrindle BW, Williams RV, Altmann K, Ghanayem NS, Margossian R, Chung WK, Border WL, Pearson GD, Stylianou MP, Mital S; Pediatric Heart Network Investigators. Enalapril in infants with single ventricle: results of a multicenter randomized trial. Circulation. 2010 Jul 27;122(4):333-40. doi: 10.1161/CIRCULATIONAHA.109.927988. Epub 2010 Jul 12.

    PMID: 20625111DERIVED

  • Hsu DT, Mital S, Ravishankar C, Margossian R, Li JS, Sleeper LA, Williams RV, Levine JC, McCrindle BW, Atz AM, Servedio D, Mahony L; Pediatric Heart Network Investigators. Rationale and design of a trial of angiotensin-converting enzyme inhibition in infants with single ventricle. Am Heart J. 2009 Jan;157(1):37-45. doi: 10.1016/j.ahj.2008.08.030.

    PMID: 19081394DERIVED

MeSH Terms

Conditions

Heart Defects, CongenitalHeart Failure

Interventions

Enalapril

Condition Hierarchy (Ancestors)

Cardiovascular AbnormalitiesCardiovascular DiseasesHeart DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

DipeptidesOligopeptidesPeptidesAmino Acids, Peptides, and Proteins

Results Point of Contact

Title
Lynn Sleeper
Organization
New England Research Institute
lsleeper@neriscience.com
617-972-3235

Study Officials

  • 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

    The Hospital for Sick Children

    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

    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

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH

Study Record Dates

First Submitted

June 3, 2005

First Posted

June 6, 2005

Study Start

August 1, 2003

Primary Completion

July 1, 2008

Study Completion

July 1, 2008

Last Updated

September 28, 2010

Results First Posted

September 16, 2010

Record last verified: 2009-09

Locations

US(8)CA(1)