Heart Defects, Congenital, Heart Failure, Congestive
Conditions
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.
Detailed description
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.
Interventions
DRUGEnalapril
Enalapril to target dose of .4mg/kg/day divided to twice per day (BID)
DRUGPlacebo
Participants will receive placebo
Sponsors
Pediatric Heart Network
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
No minimum to 45 Days
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weight-for-age Z-score at 14 Months of Age | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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. |
| B-Type Natriuretic Peptide | Measured just prior to the Glenn surgery | B-Type Natriuretic Peptide (BNP) level. |
| B-type Natriuretic Peptide Level | 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 | 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 | at 14 months of age | Neurodevelopmental status(MDI):Bayley Scales of infant development, Mental Developmental Index z-score . |
| Neurodevelopmental Status (FSII) | 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 | at 14 months of age | MacArthur-Bates Communicative Development inventory( Words and Gestures)-Phrases Understood z-score. |
| MacArthur-Bates Inventory -Words Understood | at 14 months of age | MacArthur-Bates Communicative Development inventory( Words and Gestures)-Words Understood z-score. |
| MacArthur-Bates Inventory -Total Gestures | at 14 months of age | MacArthur-Bates Communicative Development inventory( Words and Gestures)-Total Gestures z-score. |
| 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 | 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) |
| Ejection Fraction (%) | 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. |
| Ventricular Mass | just before the Glenn surgery | Two-dimensional echocardiography endpoint - Total Ventricular mass (g) per Core Laboratory assessment. |
| Ventricular Mass Z-score | just before the Glenn surgery | Two-dimensional echocardiography endpoint -Total Ventricular mass z-score per Core Laboratory assessment. |
| End-diastolic Volume | just before the Glenn surgery | Two-Dimensional Echocardiography endpoint - Total End-diastolic volume (ml) per Core Laboratory assessment. |
| End Diastolic Volume Z-score | just before the Glenn surgery | Two-dimensional echocardiography endpoint -total End diastolic volume z-score per Core Laboratory assessment. |
| End-diastolic Volume Z-score | at 14 months of age | Two-dimensional echocardiography endpoint -total end-diastolic volume z-score per Core Laboratory assessment. |
| Ventricular Mass to Volume Ratio | Measured just before the Glenn surgery | Two-Dimensional Echocardiography endpoint -Ventricular Mass to Volume ratio per Core Laboratory assessment. |
| Ventricular Filling Pressure | just before the Glenn surgery | Ventricular filling pressure measured by catherization |
| Number of Participants With Moderate to Severe AV Valve Regurgitation | just before the pre-Glenn surgery | Number of participants with Moderate to severe AV valve regurgitation. |
| MacArthur-Bates Inventory -Words Produced | at 14 months of age | MacArthur-Bates Communicative Development inventory( Words and Gestures)-Words Produced z-score. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Enalapril ACE (Angiotensin-converting enzyme) inhibitor enalapril, initial dose 0.1 mg/kg/day; Uptitrated as tolerated to target dose of 0.4 mg/kg/day given in two divided doses | 115 |
| Placebo Placebo suspension | 115 |
| Total | 230 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death or Transplant | 14 | 16 |
| Overall Study | Family or MD withdrew subject | 10 | 5 |
Baseline characteristics
| Characteristic | Total | Enalapril | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 230 Participants | 115 Participants | 115 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 20.4 days STANDARD_DEVIATION 9 | 20.1 days STANDARD_DEVIATION 8.9 | 20.7 days STANDARD_DEVIATION 9.1 |
| Race/Ethnicity, Customized Asian | 7 participants | 4 participants | 3 participants |
| Race/Ethnicity, Customized Black/African-American | 32 participants | 12 participants | 20 participants |
| Race/Ethnicity, Customized Other | 6 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized White | 185 participants | 96 participants | 89 participants |
| Region of Enrollment Canada | 21 participants | 11 participants | 10 participants |
| Region of Enrollment United States | 209 participants | 104 participants | 105 participants |
| Sex: Female, Male Female | 68 Participants | 40 Participants | 28 Participants |
| Sex: Female, Male Male | 162 Participants | 75 Participants | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 77 / 115 | 70 / 115 |
| serious Total, serious adverse events | 88 / 115 | 87 / 115 |
Outcome results
Primary
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)
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
Population: ITT, no imputation
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | Weight-for-age Z-score at 14 Months of Age | -0.62 standard deviation | Standard Error 0.13 |
| Placebo | Weight-for-age Z-score at 14 Months of Age | -0.42 standard deviation | Standard Error 0.13 |
p-value: 0.28Mixed Models Analysis
Secondary
B-Type Natriuretic Peptide
B-Type Natriuretic Peptide (BNP) level.
Time frame: Measured just prior to the Glenn surgery
Population: ITT analysis, no imputation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enalapril | B-Type Natriuretic Peptide | 79 pg/ml |
| Placebo | B-Type Natriuretic Peptide | 84 pg/ml |
p-value: 0.74Wilcoxon (Mann-Whitney)
Secondary
B-type Natriuretic Peptide Level
B-type natriuretic peptide (BNP) level.
Time frame: at the time of the 14 month visit
Population: ITT, no imputation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enalapril | B-type Natriuretic Peptide Level | 25 pg/ml |
| Placebo | B-type Natriuretic Peptide Level | 39 pg/ml |
p-value: 0.22Wilcoxon (Mann-Whitney)
Secondary
Ejection Fraction (%)
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.
Time frame: just before the Glenn surgery
Population: ITT, no imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | Ejection Fraction (%) | 57.9 percent (of end diastolic volume) | Standard Deviation 9.8 |
| Placebo | Ejection Fraction (%) | 56.6 percent (of end diastolic volume) | Standard Deviation 10.2 |
p-value: 0.36t-test, 2 sided
Secondary
Ejection Fraction (%)
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.
Time frame: at 14 months of age
Population: ITT, no imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | Ejection Fraction (%) | 59.3 percent (of end diastolic volume) | Standard Deviation 9.6 |
| Placebo | Ejection Fraction (%) | 57.9 percent (of end diastolic volume) | Standard Deviation 10.4 |
p-value: 0.37t-test, 2 sided
Secondary
End-diastolic Volume
Two-Dimensional Echocardiography endpoint - Total End-diastolic volume (ml) per Core Laboratory assessment.
Time frame: just before the Glenn surgery
Population: ITT, no imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | End-diastolic Volume | 24.1 ml | Standard Deviation 10.1 |
| Placebo | End-diastolic Volume | 23.2 ml | Standard Deviation 9 |
p-value: 0.49t-test, 2 sided
Secondary
End-diastolic Volume
Two-Dimensional Echocardiography endpoint - Total End-diastolic volume (ml) per Core Laboratory assessment.
Time frame: at 14 months of age
Population: ITT, no imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | End-diastolic Volume | 29.2 ml | Standard Deviation 10 |
| Placebo | End-diastolic Volume | 30.7 ml | Standard Deviation 11.3 |
p-value: 0.35t-test, 2 sided
Secondary
End-diastolic Volume Z-score
Two-dimensional echocardiography endpoint -total end-diastolic volume z-score per Core Laboratory assessment.
Time frame: at 14 months of age
Population: ITT, no imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | End-diastolic Volume Z-score | 1.1 standard deviation | Standard Deviation 2.1 |
| Placebo | End-diastolic Volume Z-score | 1.3 standard deviation | Standard Deviation 2.4 |
p-value: 0.43t-test, 2 sided
Secondary
End Diastolic Volume Z-score
Two-dimensional echocardiography endpoint -total End diastolic volume z-score per Core Laboratory assessment.
Time frame: just before the Glenn surgery
Population: ITT, no imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | End Diastolic Volume Z-score | 2.3 standard deviation | Standard Deviation 2.5 |
| Placebo | End Diastolic Volume Z-score | 2.1 standard deviation | Standard Deviation 2.5 |
p-value: 0.62t-test, 2 sided
Secondary
Head Circumference-for-age Z-score
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)
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
Population: ITT, no imputation
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | Head Circumference-for-age Z-score | -0.55 standard deviation | Standard Error 0.17 |
| Placebo | Head Circumference-for-age Z-score | 0.09 standard deviation | Standard Error 0.17 |
p-value: 0.008Mixed Models Analysis
Secondary
Height-for-age Z-score
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)
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
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | Height-for-age Z-score | -1.00 standard deviation | Standard Error 0.13 |
| Placebo | Height-for-age Z-score | -0.86 standard deviation | Standard Error 0.13 |
p-value: 0.42Mixed Models Analysis
Secondary
MacArthur-Bates Inventory -Phrases Understood
MacArthur-Bates Communicative Development inventory( Words and Gestures)-Phrases Understood z-score.
Time frame: at 14 months of age
Population: ITT, no imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | MacArthur-Bates Inventory -Phrases Understood | -0.48 standard deviation | Standard Deviation 1.11 |
| Placebo | MacArthur-Bates Inventory -Phrases Understood | -0.92 standard deviation | Standard Deviation 1.17 |
p-value: 0.01t-test, 2 sided
Secondary
MacArthur-Bates Inventory -Total Gestures
MacArthur-Bates Communicative Development inventory( Words and Gestures)-Total Gestures z-score.
Time frame: at 14 months of age
Population: ITT, no imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | MacArthur-Bates Inventory -Total Gestures | -0.86 standard deviation | Standard Deviation 1.07 |
| Placebo | MacArthur-Bates Inventory -Total Gestures | -1.31 standard deviation | Standard Deviation 0.97 |
p-value: 0.004t-test, 2 sided
Secondary
MacArthur-Bates Inventory -Words Produced
MacArthur-Bates Communicative Development inventory( Words and Gestures)-Words Produced z-score.
Time frame: at 14 months of age
Population: ITT, no imputation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enalapril | MacArthur-Bates Inventory -Words Produced | -0.60 standard deviation |
| Placebo | MacArthur-Bates Inventory -Words Produced | -0.63 standard deviation |
p-value: 0.31Wilcoxon (Mann-Whitney)
Secondary
MacArthur-Bates Inventory -Words Understood
MacArthur-Bates Communicative Development inventory( Words and Gestures)-Words Understood z-score.
Time frame: at 14 months of age
Population: ITT, no imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | MacArthur-Bates Inventory -Words Understood | -0.46 standard deviation | Standard Deviation 0.91 |
| Placebo | MacArthur-Bates Inventory -Words Understood | -0.82 standard deviation | Standard Deviation 0.83 |
p-value: 0.008t-test, 2 sided
Secondary
Neurodevelopmental Status (FSII)
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.
Time frame: at 14 months of age
Population: ITT, no imputation
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Enalapril | Neurodevelopmental Status (FSII) | 96.4 units on a scale |
| Placebo | Neurodevelopmental Status (FSII) | 96.4 units on a scale |
p-value: 0.6Wilcoxon (Mann-Whitney)
Secondary
Neurodevelopmental Status(MDI): Bayley Scales of Infant Development, Mental Developmental Index Z-score
Neurodevelopmental status(MDI):Bayley Scales of infant development, Mental Developmental Index z-score .
Time frame: at 14 months of age
Population: ITT, not imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | Neurodevelopmental Status(MDI): Bayley Scales of Infant Development, Mental Developmental Index Z-score | -0.26 standard deviation | Standard Deviation 0.91 |
| Placebo | Neurodevelopmental Status(MDI): Bayley Scales of Infant Development, Mental Developmental Index Z-score | -0.33 standard deviation | Standard Deviation 1.02 |
p-value: 0.6t-test, 2 sided
Secondary
Neurodevelopmental Status (PDI): the Bayley Scales of Infant Development,Psychomotor Development Index Z-score
Neurodevelopmental status (PDI): the Bayley Scales of Infant Development: Psychomotor Development index z-score .
Time frame: at 14 months of age
Population: ITT, no imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | Neurodevelopmental Status (PDI): the Bayley Scales of Infant Development,Psychomotor Development Index Z-score | -1.29 standard deviation | Standard Deviation 1.19 |
| Placebo | Neurodevelopmental Status (PDI): the Bayley Scales of Infant Development,Psychomotor Development Index Z-score | -1.32 standard deviation | Standard Deviation 1.22 |
p-value: 0.86t-test, 2 sided
Secondary
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
Population: ITT, no imputation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enalapril | Number of Participants With Moderate to Severe AV Valve Regurgitation | 11 participants |
| Placebo | Number of Participants With Moderate to Severe AV Valve Regurgitation | 22 participants |
p-value: 0.06Fisher Exact
Secondary
Number of Participants With Moderate to Severe AV Valve Regurgitation
Number of participants with Moderate to severe AV valve regurgitation.
Time frame: just before the pre-Glenn surgery
Population: ITT, no imputation
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enalapril | Number of Participants With Moderate to Severe AV Valve Regurgitation | 20 participants |
| Placebo | Number of Participants With Moderate to Severe AV Valve Regurgitation | 32 participants |
p-value: 0.08Fisher Exact
Secondary
Number of Participants With Ross Heart Failure Class I
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.
Time frame: Just prior to the pre-Glenn surgery
Population: Intention-to-treat analysis of participants measured just prior to the Glenn surgery
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enalapril | Number of Participants With Ross Heart Failure Class I | 53 Participants |
| Placebo | Number of Participants With Ross Heart Failure Class I | 56 Participants |
p-value: 1Fisher Exact
Secondary
Number of Participants With Ross Heart Failure Class I
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.
Time frame: Measured at 14 months of age
Population: Intention-to-treat analysis of participants completing the final study visit (target visit window age 14 months)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enalapril | Number of Participants With Ross Heart Failure Class I | 72 participants |
| Placebo | Number of Participants With Ross Heart Failure Class I | 77 participants |
p-value: 0.71Fisher Exact
Secondary
Ventricular Filling Pressure
Ventricular filling pressure measured by catherization
Time frame: just before the Glenn surgery
Population: ITT, no imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | Ventricular Filling Pressure | 10.9 mmHg | Standard Deviation 3.6 |
| Placebo | Ventricular Filling Pressure | 11.1 mmHg | Standard Deviation 4 |
p-value: 0.81t-test, 2 sided
Secondary
Ventricular Mass
Two-dimensional echocardiography endpoint - Total Ventricular mass (g) per Core Laboratory assessment.
Time frame: just before the Glenn surgery
Population: ITT, no imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | Ventricular Mass | 25.5 g | Standard Deviation 9.2 |
| Placebo | Ventricular Mass | 28.1 g | Standard Deviation 10.6 |
p-value: 0.08t-test, 2 sided
Secondary
Ventricular Mass
Two-Dimensional Echocardiography endpoint-Total Ventricular mass (g) per Core Laboratory assessment. Range from 15.60 to 70.40
Time frame: At 14 months of age
Population: ITT, no imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | Ventricular Mass | 31.4 g | Standard Deviation 10.3 |
| Placebo | Ventricular Mass | 34.4 g | Standard Deviation 11.4 |
p-value: 0.07t-test, 2 sided
Secondary
Ventricular Mass to Volume Ratio
Two-Dimensional Echocardiography endpoint -Ventricular Mass to Volume ratio per Core Laboratory assessment.
Time frame: Measured at 14 months of age
Population: Intention-to-treat analysis of participants completing the final study visit (target visit window age 14 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | Ventricular Mass to Volume Ratio | 1.14 g/ml | Standard Deviation 0.38 |
| Placebo | Ventricular Mass to Volume Ratio | 1.20 g/ml | Standard Deviation 0.44 |
p-value: 0.34t-test, 2 sided
Secondary
Ventricular Mass to Volume Ratio
Two-Dimensional Echocardiography endpoint -Ventricular Mass to Volume ratio per Core Laboratory assessment.
Time frame: Measured just before the Glenn surgery
Population: Intention-to-treat analysis of participants completing the pre-Glenn visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | Ventricular Mass to Volume Ratio | 1.15 g/ml | Standard Deviation 0.43 |
| Placebo | Ventricular Mass to Volume Ratio | 1.31 g/ml | Standard Deviation 0.5 |
p-value: 0.02t-test, 2 sided
Secondary
Ventricular Mass Z-score
Two-dimensional echocardiography endpoint -Total Ventricular mass z-score per Core Laboratory assessment.
Time frame: just before the Glenn surgery
Population: ITT, no imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | Ventricular Mass Z-score | 4.0 standard deviation | Standard Deviation 2.9 |
| Placebo | Ventricular Mass Z-score | 4.9 standard deviation | Standard Deviation 3.3 |
p-value: 0.05t-test, 2 sided
Secondary
Ventricular Mass Z-score
Two-dimensional echocardiography endpoint -Total Ventricular mass z-score per Core Laboratory assessment.
Time frame: at 14 months of age
Population: ITT, no imputation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Enalapril | Ventricular Mass Z-score | 2.5 standard deviation | Standard Deviation 2.3 |
| Placebo | Ventricular Mass Z-score | 3.1 standard deviation | Standard Deviation 2.5 |
p-value: 0.11t-test, 2 sided