Trial of Angiotensin Converting Enzyme Inhibition in Infants With Single Ventricle--Pediatric Heart Network (ISV)
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ClinicalTrials.gov Identifier: NCT00113087 |
Recruitment Status :
Completed
First Posted : June 6, 2005
Results First Posted : September 16, 2010
Last Update Posted : September 28, 2010
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Heart Defects, Congenital Heart Failure, Congestive | Drug: Enalapril Drug: Placebo | Phase 3 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 230 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Triple (Participant, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | Trial of ACE Inhibition in Infants With Single Ventricle (A Trial Conducted by the Pediatric Heart Network) |
Study Start Date : | August 2003 |
Actual Primary Completion Date : | July 2008 |
Actual Study Completion Date : | July 2008 |

Arm | Intervention/treatment |
---|---|
Active Comparator: Enalapril
Enalapril (angiotensin converting enzyme inhibitor)
|
Drug: Enalapril
Enalapril to target dose of .4mg/kg/day divided to twice per day (BID) |
Placebo Comparator: Placebo
Placebo (Ora-Plus and Ora-Sweet)
|
Drug: Placebo
Participants will receive placebo |
- 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)
- 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)
- 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)
- 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.
- 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.
- B-Type Natriuretic Peptide [ Time Frame: Measured just prior to the Glenn surgery ]B-Type Natriuretic Peptide (BNP) level.
- B-type Natriuretic Peptide Level [ Time Frame: at the time of the 14 month visit ]B-type natriuretic peptide (BNP) level.
- 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 .
- 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 .
- 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.
- MacArthur-Bates Inventory -Phrases Understood [ Time Frame: at 14 months of age ]MacArthur-Bates Communicative Development inventory( Words and Gestures)-Phrases Understood z-score.
- MacArthur-Bates Inventory -Words Understood [ Time Frame: at 14 months of age ]MacArthur-Bates Communicative Development inventory( Words and Gestures)-Words Understood z-score.
- MacArthur-Bates Inventory -Total Gestures [ Time Frame: at 14 months of age ]MacArthur-Bates Communicative Development inventory( Words and Gestures)-Total Gestures z-score.
- MacArthur-Bates Inventory -Words Produced [ Time Frame: at 14 months of age ]MacArthur-Bates Communicative Development inventory( Words and Gestures)-Words Produced z-score.
- 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.
- 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.
- Ventricular Mass [ Time Frame: just before the Glenn surgery ]Two-dimensional echocardiography endpoint - Total Ventricular mass (g) per Core Laboratory assessment.
- 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
- Ventricular Mass Z-score [ Time Frame: just before the Glenn surgery ]Two-dimensional echocardiography endpoint -Total Ventricular mass z-score per Core Laboratory assessment.
- Ventricular Mass Z-score [ Time Frame: at 14 months of age ]Two-dimensional echocardiography endpoint -Total Ventricular mass z-score per Core Laboratory assessment.
- End-diastolic Volume [ Time Frame: just before the Glenn surgery ]Two-Dimensional Echocardiography endpoint - Total End-diastolic volume (ml) per Core Laboratory assessment.
- End-diastolic Volume [ Time Frame: at 14 months of age ]Two-Dimensional Echocardiography endpoint - Total End-diastolic volume (ml) per Core Laboratory assessment.
- 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.
- 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.
- 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.
- 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.
- Ventricular Filling Pressure [ Time Frame: just before the Glenn surgery ]Ventricular filling pressure measured by catherization
- 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.
- 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.

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Ages Eligible for Study: | up to 45 Days (Child) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00113087
United States, Massachusetts | |
Children's Hospital Boston | |
Boston, Massachusetts, United States, 02115 | |
United States, New York | |
Columbia College of Physicians and Surgeons | |
New York, New York, United States, 10032 | |
United States, North Carolina | |
Duke University Medical Center | |
Durham, North Carolina, United States, 27710 | |
United States, Ohio | |
Cincinnati Children's Hospital Medical Center | |
Cincinnati, Ohio, United States, 45229 | |
United States, Pennsylvania | |
Children's Hospital of Philadelphia | |
Philadelphia, Pennsylvania, United States, 19104 | |
United States, South Carolina | |
Medical University of South Carolina | |
Charleston, South Carolina, United States, 29425 | |
United States, Utah | |
Primary Children's Hospital | |
Salt Lake City, Utah, United States, 84113 | |
United States, Wisconsin | |
Children's Hospital of Wisconsin | |
Milwaukee, Wisconsin, United States, 53226 | |
Canada, Ontario | |
Hospital for Sick Children | |
Toronto, Ontario, Canada, M5G 1X8 |
Principal Investigator: | 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 |
Responsible Party: | Lynn Sleeper, PI, New England Research Institutes |
ClinicalTrials.gov Identifier: | NCT00113087 |
Other Study ID Numbers: |
177 U01HL068270 ( U.S. NIH Grant/Contract ) U01HL068279 ( U.S. NIH Grant/Contract ) U01HL068281 ( U.S. NIH Grant/Contract ) U01HL068285 ( U.S. NIH Grant/Contract ) U01HL068288 ( U.S. NIH Grant/Contract ) U01HL068290 ( U.S. NIH Grant/Contract ) U01HL068292 ( U.S. NIH Grant/Contract ) U01HL068269 ( U.S. NIH Grant/Contract ) |
First Posted: | June 6, 2005 Key Record Dates |
Results First Posted: | September 16, 2010 |
Last Update Posted: | September 28, 2010 |
Last Verified: | September 2009 |
Heart Failure Univentricular Heart Heart Defects, Congenital Congenital Abnormalities Heart Diseases Cardiovascular Diseases Cardiovascular Abnormalities |
Enalapril Angiotensin-Converting Enzyme Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antihypertensive Agents |