Hypoplastic Left Heart Syndrome
Conditions
Keywords
Hypoplastic Left Heart Syndrome, HLHS, Congenital Heart Disease, Umbilical Cord Blood, UCB, Cord blood, Stem cells, Regenerative therapy, Stage II Glenn, Glenn Surgery, single ventricle
Brief summary
Researchers want to better understand what happens to the heart when the stem cells are injected directly into the muscle of the right side of the heart during the Stage II palliative surgery for single ventricle patients with hypoplastic left heart syndrome (HLHS) or HLHS variant. Researchers want to see if there are changes in the heart's structure/function following this stem cell-based therapy and compared to children that have not had cell-based therapy.
Detailed description
This is a Phase IIb trial to determine if the delivery of the autologous UCB-MNC product into the myocardium of the right ventricle of the heart at the time of Stage II surgical repair will provide an improvement in cardiac function, reaching growth and developmental milestones, and quality of life, while also providing a reduction in the cumulative days of hospitalization following Stage II surgical repair. Long-term improvement in cardiac function, reaching growth and developmental milestones, reaching Stage III surgical repair pre-op work-up, prolonging time to cardiac transplantation or death, and improving quality of life will also be determined.
Interventions
BIOLOGICALAutologous (self) mononuclear cells derived from umbilical cord blood
The investigational product will be delivered into the right myocardium via sub-epicardial injections of 0.1 mL per kg body weight to achieve the target dose of 1-3 million TNC per kg body weight.at the time of Stage II surgical repair.
PROCEDUREStage II Surgical repair
This operation usually is performed about six months after Stage I surgery to divert half of the blood to the lungs when circulation through the lungs no longer needs as much pressure from the ventricle. The shunt to the pulmonary arteries is disconnected and the right pulmonary artery is connected directly to the superior vena cava, the vein that brings deoxygenated blood from the upper part of the body to the heart. This sends half of the deoxygenated blood directly to the lungs without going through the ventricle.
Sponsors
University of Oklahoma
Children's Hospital of Philadelphia
Children's Hospital Los Angeles
Children's Hospital Colorado
Children's Hospitals and Clinics of Minnesota
Ochsner Health System
Children's of Alabama
Children's Hospital Medical Center, Cincinnati
Timothy J Nelson, MD, PhD
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 12 Months
Healthy volunteers
No
Inclusion criteria
* Diagnosis of HLHS or HLHS variant with single right ventricular dependent CHD having undergone Stage I surgical repair and undergoing Stage II surgical repair. * Less than 13 months of age at time of Stage II surgical repair * Previous participation in the UCB collection protocol with autologous UCB-MNC product that is acceptable for use (treatment arm only)
Exclusion criteria
* History of DMSO reaction (treatment arm only). * Parent(s) and/or legal guardian(s) unwilling to have their child participate or unwilling to follow the study procedures. * Severe chronic diseases at the discretion of the treating physician. * Extensive extra-cardiac syndromic features. * Known history of cancer. * Any of the following complications of his/her congenital heart disease: 1. Any condition requiring urgent, or unplanned interventional procedure within 15 days prior to Stage II surgical repair, unless complete and full cardiac recovery is documented by site investigator 2. Severe pulmonary hypertension (reported in the medical record as \>70% systemic pressure) 3. Other clinical concerns as documented by a site investigator that would predict (more likely to happen than not to happen) a risk of severe complications or very poor outcome, not directly related to the stem cell product or its injection procedure, during or after Stage II surgical repair.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Right Ventricular Cardiac Function Measured by Apical Fractional Area Change (FAC) | baseline, 3 months post-Stage II surgery | Right ventricular cardiac function as measured by echocardiogram that includes studies for apical fractional area change (FAC). Measured by percent. |
| Change in Right Ventricular Cardiac Function Measured by Circumferential Strain. | baseline, 3 months post-Stage II surgery | Right ventricular cardiac function as measured by echocardiogram that includes studies for circumferential strain. Measured by percent. |
| Change in Right Ventricular Cardiac Function Measured by Longitudinal Strain. | baseline, 3 months post-Stage II surgery | Right ventricular cardiac function as measured by echocardiogram that includes studies for longitudinal strain. Measured by percent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Heart Rate | baseline, 3-months post Stage II surgery | Change in heart rate between baseline and 3-months post Stage II surgery. Heart rate as measured at home by subject's caregiver as standard of care per subject's provider. Caregivers will be instructed by the site staff on the best way to perform. |
| Change in Oxygen Saturation | baseline, 3-months post Stage II surgery | Change in oxygen saturation between baseline and 3-months post Stage II surgery. Oxygen saturation as measured at home by subject's caregiver using the pulse oximetry device provided as standard of care by subject's provider. Caregivers will be instructed by the site to use the same pulse oximetry device for every home measurement of oxygen saturation. |
| Change in Arrhythmia and Heart Failure Medication | 3-months post-surgery | Changes in arrhythmia and heart failure medications will be recorded by caregiver on the concomitant medication diary throughout the subject's participation in the study starting at the time of consent. |
| Change in Right Ventricular Cardiac Function Measured by Apical Fractional Area Change (FAC) | baseline pre-op, hospital discharge from Stage II surgery (an average of 1-6 weeks) | Right ventricular cardiac function as measured by echocardiogram that includes studies for apical fractional area change (FAC). Measured by percent. |
| Total Time Until Listed for Cardiac Transplantation | up to Stage III surgery pre-op, approx. 4 years | The number of days between Stage II surgery and listed on cardiac transplantation list. |
| Total Time Until Death | approx 4 years | The number of days between Stage II surgery and death occurrence |
| Stage III Surgical Repair | Stage III surgery pre-op, approx. 4 years | The number of research subjects eligible for Stage III surgical repair |
| Cumulative Days of Hospitalization | 1-month post Stage II surgery | Cumulative days of hospitalization per patient following discharge for the Stage II surgical repair. |
| Change in Weight | baseline, 3-months post Stage II surgery | Change in weight between baseline and 3-months post Stage II surgery. Weight as measured by scale provided as part of standard of care by subject's provider. Measured at home by subject's caregiver using the same scale for every home measurement of body weight. Caregivers will be instructed by the site to use the same scale for every home measurement of body weight. Scales will vary based on the institution's standard name/type used. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from May 2019 through January 2022 from the following eight sites: Children's Hospital Colorado, Children's Hospital Los Angeles, Children's Hospital of Alabama, Children's Hospital of Philadelphia, Children's Hospitals and Clinics of Minnesota - Minneapolis, Cincinnati Children's Hospital Medical Center, Ochsner Medical Center Jefferson, and Oklahoma University Medical Center.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Autologous (self) mononuclear cells derived from umbilical cord blood and that meet all release criteria are injected into the surface of the right heart muscle to achieve the target dose of 1-3 million cells per kilogram body weight . This is a one time treatment at the time of Stage II Glenn surgery .
Autologous (self) mononuclear cells derived from umbilical cord blood: The investigational product will be delivered into the right myocardium via sub-epicardial injections of 0.1 mL per kg body weight to achieve the target dose of 1-3 million TNC per kg body weight.at the time of Stage II surgical repair.
Stage II Surgical repair: This operation usually is performed about six months after Stage I surgery to divert half of the blood to the lungs when circulation through the lungs no longer needs as much pressure from the ventricle. The shunt to the pulmonary arteries is disconnected and the right pulmonary artery is connected directly to the superior vena cava, the vein that brings deoxygenated blood from the upper part of the body to the heart. This sends half of the deoxygenated blood directly to the lungs without going through the ventricle. | 50 |
| Control Clinical data will be collected before, during and after the Stage II surgical standard of care procedure. Requires additional imaging studies at 3 months that are not standard of care in addition to some blood tests that would be beyond standard of care. Information will be collected to document the clinical outcomes and will be compared with the information from the group receiving the investigational treatment used in this study.
Stage II Surgical repair: This operation usually is performed about six months after Stage I surgery to divert half of the blood to the lungs when circulation through the lungs no longer needs as much pressure from the ventricle. The shunt to the pulmonary arteries is disconnected and the right pulmonary artery is connected directly to the superior vena cava, the vein that brings deoxygenated blood from the upper part of the body to the heart. This sends half of the deoxygenated blood directly to the lungs without going through the ventricle. | 45 |
| Total | 95 |
Baseline characteristics
| Characteristic | Treatment | Control | Total |
|---|---|---|---|
| Age, Continuous | 5.1 months STANDARD_DEVIATION 1.5 | 5.8 months STANDARD_DEVIATION 2.2 | 5.4 months STANDARD_DEVIATION 1.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 11 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants | 28 Participants | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 6 Participants | 10 Participants |
| Fractional Area Change (%) | 41.2 percentage of area STANDARD_DEVIATION 6.4 | 41.3 percentage of area STANDARD_DEVIATION 5.8 | 41.2 percentage of area STANDARD_DEVIATION 6.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 10 Participants | 15 Participants |
| Race (NIH/OMB) White | 36 Participants | 29 Participants | 65 Participants |
| Sex: Female, Male Female | 11 Participants | 20 Participants | 31 Participants |
| Sex: Female, Male Male | 39 Participants | 25 Participants | 64 Participants |
| Troponin T (ng/mL) | 0.065 ng/mL STANDARD_DEVIATION 0.185 | 0.037 ng/mL STANDARD_DEVIATION 0.052 | 0.051 ng/mL STANDARD_DEVIATION 0.136 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 50 | 3 / 45 |
| other Total, other adverse events | 48 / 50 | 45 / 45 |
| serious Total, serious adverse events | 38 / 50 | 27 / 45 |
Outcome results
Primary
Change in Right Ventricular Cardiac Function Measured by Apical Fractional Area Change (FAC)
Right ventricular cardiac function as measured by echocardiogram that includes studies for apical fractional area change (FAC). Measured by percent.
Time frame: baseline, 12 months post-Stage II surgery
Population: All enrolled subjects with both baseline and 12-month fractional area changes values, as assessed by echocardiogram.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment | Change in Right Ventricular Cardiac Function Measured by Apical Fractional Area Change (FAC) | -3.8975 percentage of area |
| Control | Change in Right Ventricular Cardiac Function Measured by Apical Fractional Area Change (FAC) | -4.4310 percentage of area |
Comparison: Analysis of covariance (ANCOVA), adjusted for baseline FAC, is used to assess change in FAC from baseline to 12-months post-surgery.p-value: 0.6765ANCOVA
Primary
Change in Right Ventricular Cardiac Function Measured by Apical Fractional Area Change (FAC)
Right ventricular cardiac function as measured by echocardiogram that includes studies for apical fractional area change (FAC). Measured by percent.
Time frame: baseline, 3 months post-Stage II surgery
Population: All enrolled subjects with both a baseline and 3-month Fractional Area Change value as assessed by Echocardiogram.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment | Change in Right Ventricular Cardiac Function Measured by Apical Fractional Area Change (FAC) | -2.2258 percentage of area |
| Control | Change in Right Ventricular Cardiac Function Measured by Apical Fractional Area Change (FAC) | -2.5116 percentage of area |
Comparison: Analysis of covariance (ANCOVA), adjusted for baseline FAC, is used to assess change in FAC from baseline to 3-months post-surgery.p-value: 0.8095ANCOVA
Primary
Change in Right Ventricular Cardiac Function Measured by Circumferential Strain.
Right ventricular cardiac function as measured by echocardiogram that includes studies for circumferential strain. Measured by percent.
Time frame: baseline, 3 months post-Stage II surgery
Population: All enrolled subjects with both baseline and 3-month circumferential strain values as assessed by echocardiogram.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment | Change in Right Ventricular Cardiac Function Measured by Circumferential Strain. | 1.3412 percentage of area |
| Control | Change in Right Ventricular Cardiac Function Measured by Circumferential Strain. | 0.1704 percentage of area |
Comparison: Analysis of covariance (ANCOVA), adjusted for baseline circumferential strain, is used to assess change in circumferential strain from baseline to 3-months post-surgery.p-value: 0.3029ANCOVA
Primary
Change in Right Ventricular Cardiac Function Measured by Longitudinal Strain.
Right ventricular cardiac function as measured by echocardiogram that includes studies for longitudinal strain. Measured by percent.
Time frame: baseline, 3 months post-Stage II surgery
Population: All enrolled subjects with both baseline and 3-month longitudinal strain values as assessed by echocardiogram.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment | Change in Right Ventricular Cardiac Function Measured by Longitudinal Strain. | 0.5394 percentage of area |
| Control | Change in Right Ventricular Cardiac Function Measured by Longitudinal Strain. | -1.2407 percentage of area |
Comparison: Analysis of covariance (ANCOVA), adjusted for baseline longitudinal strain, is used to assess change in longitudinal strain from baseline to 3-months post-surgery.p-value: 0.0323ANCOVA
Secondary
Change in Arrhythmia and Heart Failure Medication
Changes in arrhythmia and heart failure medications will be recorded by caregiver on the concomitant medication diary throughout the subject's participation in the study starting at the time of consent.
Time frame: 3-months post-surgery
Population: All enrolled subjects.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Treatment | Change in Arrhythmia and Heart Failure Medication | Endotelin receptor antagonist | Not Prescribed | 49 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Antiarrythmic Class IC | Not Prescribed | 48 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Endotelin receptor antagonist | Same | 1 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | ACE Inhibitor | Decrease | 1 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Loop diuretic | Decrease | 1 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Antiarrythmic Class IC | Same | 2 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Loop diuretic | Increase | 25 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Aldosterone receptor antagonis | Increase | 5 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Loop diuretic | Not Prescribed | 21 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Antiarrythmic Class III | Decrease | 0 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Loop diuretic | Same | 3 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | ACE Inhibitor | Not Prescribed | 31 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Na+/K+ ATPase inhibitor | Decrease | 1 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Antiarrythmic Class III | Increase | 0 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Na+/K+ ATPase inhibitor | Increase | 10 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Aldosterone receptor antagonis | Not Prescribed | 45 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Na+/K+ ATPase inhibitor | Not Prescribed | 34 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Antiarrythmic Class III | Not Prescribed | 46 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Na+/K+ ATPase inhibitor | Same | 5 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | B-blocker | Same | 2 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | PDE-3 inhibitor | Decrease | 0 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Antiarrythmic Class III | Same | 4 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | PDE-3 inhibitor | Increase | 1 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Aldosterone receptor antagonis | Same | 0 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | PDE-3 inhibitor | Not Prescribed | 49 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | B-blocker | Decrease | 0 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | PDE-3 inhibitor | Same | 0 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | ACE Inhibitor | Same | 5 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | PDE-5 inhibitor | Decrease | 0 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | B-blocker | Increase | 2 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | PDE-5 inhibitor | Increase | 10 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Antiarrythmic Class IC | Decrease | 0 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | PDE-5 inhibitor | Not Prescribed | 39 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | B-blocker | Not Prescribed | 46 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | PDE-5 inhibitor | Same | 1 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Endotelin receptor antagonist | Decrease | 0 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Thiazide diuretic | Decrease | 0 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | ACE Inhibitor | Increase | 13 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Thiazide diuretic | Increase | 5 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Endotelin receptor antagonist | Increase | 0 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Thiazide diuretic | Not Prescribed | 45 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Aldosterone receptor antagonis | Decrease | 0 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Thiazide diuretic | Same | 0 Participants |
| Treatment | Change in Arrhythmia and Heart Failure Medication | Antiarrythmic Class IC | Increase | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Thiazide diuretic | Same | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | B-blocker | Not Prescribed | 41 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | B-blocker | Same | 3 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | ACE Inhibitor | Decrease | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | ACE Inhibitor | Increase | 14 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | ACE Inhibitor | Not Prescribed | 24 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | ACE Inhibitor | Same | 7 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Aldosterone receptor antagonis | Decrease | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Aldosterone receptor antagonis | Increase | 4 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Aldosterone receptor antagonis | Not Prescribed | 41 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Aldosterone receptor antagonis | Same | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Antiarrythmic Class IC | Decrease | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Antiarrythmic Class IC | Increase | 1 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Antiarrythmic Class IC | Not Prescribed | 44 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Antiarrythmic Class IC | Same | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Antiarrythmic Class III | Decrease | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Antiarrythmic Class III | Increase | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Antiarrythmic Class III | Not Prescribed | 45 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Antiarrythmic Class III | Same | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | B-blocker | Decrease | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | B-blocker | Increase | 1 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Endotelin receptor antagonist | Decrease | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Endotelin receptor antagonist | Increase | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Endotelin receptor antagonist | Not Prescribed | 44 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Endotelin receptor antagonist | Same | 1 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Loop diuretic | Decrease | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Loop diuretic | Increase | 20 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Loop diuretic | Not Prescribed | 20 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Loop diuretic | Same | 5 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Na+/K+ ATPase inhibitor | Decrease | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Na+/K+ ATPase inhibitor | Increase | 4 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Na+/K+ ATPase inhibitor | Not Prescribed | 32 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Na+/K+ ATPase inhibitor | Same | 9 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | PDE-3 inhibitor | Decrease | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | PDE-3 inhibitor | Increase | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | PDE-3 inhibitor | Not Prescribed | 45 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | PDE-3 inhibitor | Same | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | PDE-5 inhibitor | Decrease | 3 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | PDE-5 inhibitor | Increase | 10 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | PDE-5 inhibitor | Not Prescribed | 28 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | PDE-5 inhibitor | Same | 4 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Thiazide diuretic | Decrease | 0 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Thiazide diuretic | Increase | 3 Participants |
| Control | Change in Arrhythmia and Heart Failure Medication | Thiazide diuretic | Not Prescribed | 42 Participants |
Secondary
Change in Heart Rate
Change in heart rate between baseline and 3-months post Stage II surgery. Heart rate as measured at home by subject's caregiver as standard of care per subject's provider. Caregivers will be instructed by the site staff on the best way to perform.
Time frame: baseline, 3-months post Stage II surgery
Population: All enrolled subjects with heart rate values at both baseline and 3-months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Heart Rate | 3.2 beats per minute | Standard Deviation 14.5 |
| Control | Change in Heart Rate | 4.6 beats per minute | Standard Deviation 21.2 |
Comparison: Kruskal-Wallis test for change in heart rate from baseline to 3-months post-surgery.p-value: 0.9095Kruskal-Wallis
Secondary
Change in Oxygen Saturation
Change in oxygen saturation between baseline and 3-months post Stage II surgery. Oxygen saturation as measured at home by subject's caregiver using the pulse oximetry device provided as standard of care by subject's provider. Caregivers will be instructed by the site to use the same pulse oximetry device for every home measurement of oxygen saturation.
Time frame: baseline, 3-months post Stage II surgery
Population: All enrolled subjects with oxygen saturation values at both baseline and 3-months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Oxygen Saturation | 4.9 percentage of saturation | Standard Deviation 7.3 |
| Control | Change in Oxygen Saturation | 5.7 percentage of saturation | Standard Deviation 6.6 |
Comparison: Kruskal-Wallis test for change in oxygen saturation from baseline to 3-months post-surgery.p-value: 0.6391Kruskal-Wallis
Secondary
Change in Right Ventricular Cardiac Function Measured by Apical Fractional Area Change (FAC)
Right ventricular cardiac function as measured by echocardiogram that includes studies for apical fractional area change (FAC). Measured by percent.
Time frame: baseline, Stage III surgery pre-op
Secondary
Change in Right Ventricular Cardiac Function Measured by Apical Fractional Area Change (FAC)
Right ventricular cardiac function as measured by echocardiogram that includes studies for apical fractional area change (FAC). Measured by percent.
Time frame: baseline pre-op, hospital discharge from Stage II surgery (an average of 1-6 weeks)
Population: All enrolled subjects with both baseline and discharge fractional area change values, as assessed by echocardiogram.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment | Change in Right Ventricular Cardiac Function Measured by Apical Fractional Area Change (FAC) | -1.8109 percentage of area |
| Control | Change in Right Ventricular Cardiac Function Measured by Apical Fractional Area Change (FAC) | -3.0902 percentage of area |
Comparison: Analysis of covariance (ANCOVA), adjusted for baseline FAC, is used to assess change in FAC from baseline to discharge.p-value: 0.3456ANCOVA
Secondary
Change in Weight
Change in weight between baseline and 3-months post Stage II surgery. Weight as measured by scale provided as part of standard of care by subject's provider. Measured at home by subject's caregiver using the same scale for every home measurement of body weight. Caregivers will be instructed by the site to use the same scale for every home measurement of body weight. Scales will vary based on the institution's standard name/type used.
Time frame: baseline, 3-months post Stage II surgery
Population: All enrolled subjects with weight values at both baseline and 3-months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Change in Weight | 1.4 kg | Standard Deviation 1.3 |
| Control | Change in Weight | 1.3 kg | Standard Deviation 0.7 |
Comparison: Kruskal-Wallis test for change in weight from baseline to 3-months post-surgery.p-value: 0.9563Kruskal-Wallis
Secondary
Change in Weight
Weight as measured by scale provided as part of standard of care by subject's provider. Measured at home by subject's caregiver using the same scale for every home measurement of body weight. Caregivers will be instructed by the site to use the same scale for every home measurement of body weight. Scales will vary based on the institution's standard name/type used.
Time frame: baseline, every 6 months post-Stage II surgery
Population: Enrolled subjects with weight values available at each 6-month follow-up visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Change in Weight | 6-months | 8.1 kg | Standard Deviation 1.35 |
| Treatment | Change in Weight | 18-months | 11.0 kg | Standard Deviation 1.49 |
| Treatment | Change in Weight | 12-months | 9.7 kg | Standard Deviation 1.38 |
| Treatment | Change in Weight | 24-months | 12.0 kg | Standard Deviation 1.92 |
| Treatment | Change in Weight | Baseline | 6.1 kg | Standard Deviation 0.8 |
| Control | Change in Weight | 24-months | 12.2 kg | Standard Deviation 1.82 |
| Control | Change in Weight | Baseline | 6.2 kg | Standard Deviation 1.2 |
| Control | Change in Weight | 6-months | 8.4 kg | Standard Deviation 1.27 |
| Control | Change in Weight | 12-months | 9.6 kg | Standard Deviation 1.3 |
| Control | Change in Weight | 18-months | 10.9 kg | Standard Deviation 1.64 |
Secondary
Cumulative Days of Hospitalization
Cumulative days of hospitalization per patient following discharge for the Stage II surgical repair.
Time frame: 3-months post Stage II surgery
Population: All enrolled subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Cumulative Days of Hospitalization | 20.7 days | Standard Deviation 26 |
| Control | Cumulative Days of Hospitalization | 15.6 days | Standard Deviation 15.9 |
Comparison: Kruskal-Wallis test comparing number of days in hospital post stage-II surgeryp-value: 0.8782Kruskal-Wallis
Secondary
Cumulative Days of Hospitalization
Cumulative days of hospitalization per patient following discharge for the Stage II surgical repair.
Time frame: 1-month post Stage II surgery
Population: All enrolled subjects.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Cumulative Days of Hospitalization | 13.2 days | Standard Deviation 9.6 |
| Control | Cumulative Days of Hospitalization | 13.3 days | Standard Deviation 9.1 |
Comparison: Kruskal-Wallis test comparing number of days in hospital post stage-II surgery.p-value: 0.776Kruskal-Wallis
Secondary
Stage III Surgical Repair
The number of research subjects eligible for Stage III surgical repair
Time frame: Stage III surgery pre-op, approx. 4 years
Secondary
Total Time Until Death
The number of days between Stage II surgery and death occurrence
Time frame: approx 4 years
Secondary
Total Time Until Listed for Cardiac Transplantation
The number of days between Stage II surgery and listed on cardiac transplantation list.
Time frame: up to Stage III surgery pre-op, approx. 4 years