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Completed

NCT Number: NCT00113087

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

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.

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Key information

Conditions

Heart Defects, Congenital Cardiovascular Abnormalities Cardiovascular Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Heart Diseases Heart Failure Heart Failure, Congestive

Age range

Up to 45 day

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Hospital for Sick Children, Toronto, Ontario, Canada

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Enalapril

Drug

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

Placebo

Drug

Participants will receive placebo

Primary outcomes

  1. Weight-for-age Z-score at 14 Months of Age

    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

    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 outcomes

  1. Height-for-age Z-score

    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

    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)

  2. Head Circumference-for-age Z-score

    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

    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)

  3. Number of Participants With Ross Heart Failure Class I

    Time frame: Just prior to the pre-Glenn surgery

    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.

  4. Number of Participants With Ross Heart Failure Class I

    Time frame: 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.

  5. B-Type Natriuretic Peptide

    Time frame: Measured just prior to the Glenn surgery

    B-Type Natriuretic Peptide (BNP) level.

  6. B-type Natriuretic Peptide Level

    Time frame: at the time of the 14 month visit

    B-type natriuretic peptide (BNP) level.

  7. Neurodevelopmental Status (PDI): the Bayley Scales of Infant Development,Psychomotor Development Index Z-score

    Time frame: at 14 months of age

    Neurodevelopmental status (PDI):

    the Bayley Scales of Infant Development: Psychomotor Development index z-score .

  8. Neurodevelopmental Status(MDI): Bayley Scales of Infant Development, Mental Developmental Index Z-score

    Time frame: at 14 months of age

    Neurodevelopmental status(MDI):Bayley Scales of infant development, Mental Developmental Index z-score .

  9. Neurodevelopmental Status (FSII)

    Time frame: 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.

  10. MacArthur-Bates Inventory -Phrases Understood

    Time frame: at 14 months of age

    MacArthur-Bates Communicative Development inventory( Words and Gestures)-Phrases Understood z-score.

  11. MacArthur-Bates Inventory -Words Understood

    Time frame: at 14 months of age

    MacArthur-Bates Communicative Development inventory( Words and Gestures)-Words Understood z-score.

  12. MacArthur-Bates Inventory -Total Gestures

    Time frame: at 14 months of age

    MacArthur-Bates Communicative Development inventory( Words and Gestures)-Total Gestures z-score.

  13. MacArthur-Bates Inventory -Words Produced

    Time frame: at 14 months of age

    MacArthur-Bates Communicative Development inventory( Words and Gestures)-Words Produced z-score.

  14. Ejection Fraction (%)

    Time frame: just before the Glenn surgery

    Two-dimensional echocardiography endpoint -Total Ejection Fraction (%) per Core Laboratory assessment. Ejection Fraction % is defined as the percentage of the stroke volume (i.e. difference between end-diastolic and end-systolic volumes) in a ventricle relative to end-diastolic volume.

  15. Ejection Fraction (%)

    Time frame: 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.

  16. Ventricular Mass

    Time frame: just before the Glenn surgery

    Two-dimensional echocardiography endpoint - Total Ventricular mass (g) per Core Laboratory assessment.

  17. Ventricular Mass

    Time frame: At 14 months of age

    Two-Dimensional Echocardiography endpoint-Total Ventricular mass (g) per Core Laboratory assessment. Range from 15.60 to 70.40

  18. Ventricular Mass Z-score

    Time frame: just before the Glenn surgery

    Two-dimensional echocardiography endpoint -Total Ventricular mass z-score per Core Laboratory assessment.

  19. Ventricular Mass Z-score

    Time frame: at 14 months of age

    Two-dimensional echocardiography endpoint -Total Ventricular mass z-score per Core Laboratory assessment.

  20. End-diastolic Volume

    Time frame: just before the Glenn surgery

    Two-Dimensional Echocardiography endpoint - Total End-diastolic volume (ml) per Core Laboratory assessment.

  21. End-diastolic Volume

    Time frame: at 14 months of age

    Two-Dimensional Echocardiography endpoint - Total End-diastolic volume (ml) per Core Laboratory assessment.

  22. End Diastolic Volume Z-score

    Time frame: just before the Glenn surgery

    Two-dimensional echocardiography endpoint -total End diastolic volume z-score per Core Laboratory assessment.

  23. End-diastolic Volume Z-score

    Time frame: at 14 months of age

    Two-dimensional echocardiography endpoint -total end-diastolic volume z-score per Core Laboratory assessment.

  24. Ventricular Mass to Volume Ratio

    Time frame: Measured just before the Glenn surgery

    Two-Dimensional Echocardiography endpoint -Ventricular Mass to Volume ratio per Core Laboratory assessment.

  25. Ventricular Mass to Volume Ratio

    Time frame: Measured at 14 months of age

    Two-Dimensional Echocardiography endpoint -Ventricular Mass to Volume ratio per Core Laboratory assessment.

  26. Ventricular Filling Pressure

    Time frame: just before the Glenn surgery

    Ventricular filling pressure measured by catherization

  27. Number of Participants With Moderate to Severe AV Valve Regurgitation

    Time frame: just before the pre-Glenn surgery

    Number of participants with Moderate to severe AV valve regurgitation.

  28. Number of Participants With Moderate to Severe AV Valve Regurgitation

    Time frame: at age 14 months

    Number of participants with moderate to severe AV valve regurgitation.

Sponsors and collaborators

Lead sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Nih

Collaborators

  • Pediatric Heart Network

Registry information

Official study title

Trial of ACE Inhibition in Infants With Single Ventricle (A Trial Conducted by the Pediatric Heart Network)

Acronym: ISV

Important dates

Study start
2003
Primary completion
2008
Study completion
2008
First posted
Jun 6, 2005
Registry last updated
Sep 28, 2010

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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