Milwaukee, Wisconsin 53226

  • Heart Failure, Congestive

Purpose:

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.


Study summary:

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.


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


Study is Available At:


Original ID:

177


NCT ID:

NCT00113087


Secondary ID:

U01HL068270


Study Acronym:

ISV


Brief Title:

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


Official Title:

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


Overall Status:

Completed


Study Phase:

Phase 3


Genders:

Both


Minimum Age:

N/A


Maximum Age:

45 Days


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Heart, Lung, and Blood Institute (NHLBI)


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Allocation: Randomized, Endpoint Classification:


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

230


Enrollment Type:

Actual


Overall Contact Information

Official Name:Page Anderson, MD
Principal Investigator
Duke University Medical Center, Durham, NC

Study Dates

Start Date:August 2003
Completion Date:July 2008
Completion Type:Actual
Primary Completion Date:July 2008
Primary Completion Type:Actual
Verification Date:September 2009
Last Changed Date:September 16, 2010
First Received Date:June 3, 2005
First Results Date:September 4, 2009

Study Outcomes

Outcome Type:Primary Outcome
Measure: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 aft
Safety Issues:False
Description: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)
Outcome Type:Secondary Outcome
Measure:Height-for-age Z-score
Time Frame:Measured at baseline, 2 weeks after starting study drug, just prior to the Glenn surgery, 7 days aft
Safety Issues:False
Description: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)
Outcome Type:Secondary Outcome
Measure: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 aft
Safety Issues:False
Description: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)
Outcome Type:Secondary Outcome
Measure:Number of Participants With Ross Heart Failure Class I
Time Frame:Just prior to the pre-Glenn surgery
Safety Issues:True
Description: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.
Outcome Type:Secondary Outcome
Measure:Number of Participants With Ross Heart Failure Class I
Time Frame:Measured at 14 months of age
Safety Issues:False
Description: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.
Outcome Type:Secondary Outcome
Measure:B-Type Natriuretic Peptide
Time Frame:Measured just prior to the Glenn surgery
Safety Issues:False
Description:B-Type Natriuretic Peptide (BNP) level.
Outcome Type:Secondary Outcome
Measure:B-type Natriuretic Peptide Level
Time Frame:at the time of the 14 month visit
Safety Issues:False
Description:B-type natriuretic peptide (BNP) level.
Outcome Type:Secondary Outcome
Measure:Neurodevelopmental Status (PDI): the Bayley Scales of Infant Development,Psychomotor Development Index Z-score
Time Frame:at 14 months of age
Safety Issues:False
Description:Neurodevelopmental status (PDI): the Bayley Scales of Infant Development: Psychomotor Development index z-score .
Outcome Type:Secondary Outcome
Measure:Neurodevelopmental Status(MDI): Bayley Scales of Infant Development, Mental Developmental Index Z-score
Time Frame:at 14 months of age
Safety Issues:False
Description:Neurodevelopmental status(MDI):Bayley Scales of infant development, Mental Developmental Index z-score .
Outcome Type:Secondary Outcome
Measure:Neurodevelopmental Status (FSII)
Time Frame:at 14 months of age
Safety Issues:False
Description: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.
Outcome Type:Secondary Outcome
Measure:MacArthur-Bates Inventory -Phrases Understood
Time Frame:at 14 months of age
Safety Issues:False
Description:MacArthur-Bates Communicative Development inventory( Words and Gestures)-Phrases Understood z-score.
Outcome Type:Secondary Outcome
Measure:MacArthur-Bates Inventory -Words Understood
Time Frame:at 14 months of age
Safety Issues:False
Description:MacArthur-Bates Communicative Development inventory( Words and Gestures)-Words Understood z-score.
Outcome Type:Secondary Outcome
Measure:MacArthur-Bates Inventory -Total Gestures
Time Frame:at 14 months of age
Safety Issues:False
Description:MacArthur-Bates Communicative Development inventory( Words and Gestures)-Total Gestures z-score.
Outcome Type:Secondary Outcome
Measure:MacArthur-Bates Inventory -Words Produced
Time Frame:at 14 months of age
Safety Issues:False
Description:MacArthur-Bates Communicative Development inventory( Words and Gestures)-Words Produced z-score.
Outcome Type:Secondary Outcome
Measure:Ejection Fraction (%)
Time Frame:just before the Glenn surgery
Safety Issues:False
Description: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 r
Outcome Type:Secondary Outcome
Measure:Ejection Fraction (%)
Time Frame:at 14 months of age
Safety Issues:False
Description: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)rela
Outcome Type:Secondary Outcome
Measure:Ventricular Mass
Time Frame:just before the Glenn surgery
Safety Issues:False
Description:Two-dimensional echocardiography endpoint - Total Ventricular mass (g) per Core Laboratory assessment.
Outcome Type:Secondary Outcome
Measure:Ventricular Mass
Time Frame:At 14 months of age
Safety Issues:False
Description:Two-Dimensional Echocardiography endpoint-Total Ventricular mass (g) per Core Laboratory assessment. Range from 15.60 to 70.40
Outcome Type:Secondary Outcome
Measure:Ventricular Mass Z-score
Time Frame:just before the Glenn surgery
Safety Issues:False
Description:Two-dimensional echocardiography endpoint -Total Ventricular mass z-score per Core Laboratory assessment.
Outcome Type:Secondary Outcome
Measure:Ventricular Mass Z-score
Time Frame:at 14 months of age
Safety Issues:False
Description:Two-dimensional echocardiography endpoint -Total Ventricular mass z-score per Core Laboratory assessment.
Outcome Type:Secondary Outcome
Measure:End-diastolic Volume
Time Frame:just before the Glenn surgery
Safety Issues:False
Description:Two-Dimensional Echocardiography endpoint - Total End-diastolic volume (ml) per Core Laboratory assessment.
Outcome Type:Secondary Outcome
Measure:End-diastolic Volume
Time Frame:at 14 months of age
Safety Issues:False
Description:Two-Dimensional Echocardiography endpoint - Total End-diastolic volume (ml) per Core Laboratory assessment.
Outcome Type:Secondary Outcome
Measure:End Diastolic Volume Z-score
Time Frame:just before the Glenn surgery
Safety Issues:False
Description:Two-dimensional echocardiography endpoint -total End diastolic volume z-score per Core Laboratory assessment.
Outcome Type:Secondary Outcome
Measure:End-diastolic Volume Z-score
Time Frame:at 14 months of age
Safety Issues:False
Description:Two-dimensional echocardiography endpoint -total end-diastolic volume z-score per Core Laboratory assessment.
Outcome Type:Secondary Outcome
Measure:Ventricular Mass to Volume Ratio
Time Frame:Measured just before the Glenn surgery
Safety Issues:False
Description:Two-Dimensional Echocardiography endpoint -Ventricular Mass to Volume ratio per Core Laboratory assessment.
Outcome Type:Secondary Outcome
Measure:Ventricular Mass to Volume Ratio
Time Frame:Measured at 14 months of age
Safety Issues:False
Description:Two-Dimensional Echocardiography endpoint -Ventricular Mass to Volume ratio per Core Laboratory assessment.
Outcome Type:Secondary Outcome
Measure:Ventricular Filling Pressure
Time Frame:just before the Glenn surgery
Safety Issues:False
Description:Ventricular filling pressure measured by catherization
Outcome Type:Secondary Outcome
Measure:Number of Participants With Moderate to Severe AV Valve Regurgitation
Time Frame:just before the pre-Glenn surgery
Safety Issues:False
Description:Number of participants with Moderate to severe AV valve regurgitation.
Outcome Type:Secondary Outcome
Measure:Number of Participants With Moderate to Severe AV Valve Regurgitation
Time Frame:at age 14 months
Safety Issues:False
Description:Number of participants with moderate to severe AV valve regurgitation.

Study Interventions

Intervention Type:Drug
Name:Enalapril
Description:Enalapril to target dose of .4mg/kg/day divided to twice per day (BID)
Arm Name:Enalapril
Other Name:Enalapril
Intervention Type:Drug
Name:Placebo
Description:Participants will receive placebo
Arm Name:Placebo
Other Name:placebo

Study Arms

Study Arm Type:Active Comparator
Arm Name:Enalapril
Description:Enalapril (angiotensin converting enzyme inhibitor)
Study Arm Type:Placebo Comparator
Arm Name:Placebo
Description:Placebo (Ora-Plus and Ora-Sweet)

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Heart, Lung, and Blood Institute (NHLBI)
Agency Class:Other
Agency Type:Collaborator
Agency Name:Pediatric Heart Network

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: April 03, 2020

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