The CHILD Trial: Hypoplastic Left Heart Syndrome Study.

Study Overview
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Brief Summary
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The objectives of this pilot study are to evaluate the feasibility and safety of intramyocardial injection of autologous c-kit+ cells during the Stage II BDCPA operation and to observe effects on clinical outcome including right ventricular myocardial function, severity of tricuspid regurgitation, incidence of serious adverse events, re-hospitalizations, changes in health status, the need for transplantation, or mortality.

Official Title
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Autologous Cardiac Stem Cell Injection in Patients With Hypoplastic Left Heart Syndrome: An Open Label Pilot Study.

Conditions
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Hypoplastic Left Heart Syndrome

Intervention / Treatment
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* Biological: c-kit+ cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For inclusion in the study, subjects must meet all of the inclusion criteria: Subjects with hypoplastic left heart syndrome (all types) requiring Stage I Norwood operation. Exclusion Criteria: Candidates will be excluded from the study if any of the following conditions are met: Subjects undergoing the Stage I Norwood operation who do not have HLHS. Subjects requiring mechanical circulatory support immediately prior to Stage II BDCPA operation (within 5 days). Parent or guardian unwilling or unable to comply with necessary follow-up(s). Mother is serum positive for HIV 1/2, hepatitis BsAg or viremic hepatitis C and Treponema pallidum. Subjects who are unsuitable for inclusion in the study in the opinion of the investigator(s).

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 21 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The first 10 participants will be enrolled in Group A to assess safety and feasibility. An additional 22 participants will be enrolled in Group B and will be randomized to either the Treatment or Control Group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open label C-kit+ cells Group A<br>Group A is an open-label treatment group determining safety and feasibility. Participants enrolled in this group will be receiving previously harvested c-kit+ cells during their Stage II BDCPA operation. Harvested c-kit+ cells will be injected into the right ventricle directly intramyocardially. | Biological: c-kit+ cells<br>* The autologous c-kit+ cells will be harvested from participant's right atrial tissue obtained from participant's SOC Norwood Operation. The harvested c-kit+ cells containing up to a total of 12,500 cells/kg will be delivered through 6-10 intramyocardial injections of approximately 100uL per injection for a total volume of approximately 0.6 mL.<br>* Other names: Autologous c-kit-positive cells (c-kit+ cells);|
| Active Comparator: C-kit+ cells Group B<br>Participants randomized to Group B Treatment Group will receive previously harvested c-kit+ cells during their Stage II BDCPA operation. Harvested c-kit+ cells will be injected into the right ventricle directly intramyocardially. | Biological: c-kit+ cells<br>* The autologous c-kit+ cells will be harvested from participant's right atrial tissue obtained from participant's SOC Norwood Operation. The harvested c-kit+ cells containing up to a total of 12,500 cells/kg will be delivered through 6-10 intramyocardial injections of approximately 100uL per injection for a total volume of approximately 0.6 mL.<br>* Other names: Autologous c-kit-positive cells (c-kit+ cells);|
| No Intervention: No Intervention Group<br>Participants randomized to Group B Control Group will receive only their standard of care (SOC) Stage II BDCPA operation without the injection of harvested c-kit+ cells. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Incidence of Treatment Related Major Adverse Cardiac Events | Safety will be reported as the number of incidence of treatment related major adverse cardiac events (MACE). MACE is defined as any of the following: greater than 30 seconds of sustained/symptomatic ventricular tachycardia requiring intervention, cardiogenic shock, unplanned cardiovascular operation due to injection site bleeding, need for new permanent pacemaker, stroke or embolic event to the brain determined by CT scan and death. MACE will be evaluated by the treating physician and assessed using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5. | 30 days | 
| Number of c-kit+ products | Feasibility will be reported as the number of c-kit+ products that can be manufactured and delivered to subjects | Day 1 | 
| Number of participants completing Magnetic Resonance Imaging (MRI) | Feasibility will be reported as the number of participants that complete the baseline, 6-months, and 12-months follow up MRI. | 12 months | 
| Change in right ventricular function | Efficacy will be reported as the change in right ventricular function assessed as a percentage and will be measuring using serial echocardiograms and MRI scan. | Baseline, 12 months | 
| Change in Right Ventricular End-diastolic Volume | Efficacy will be reported as the change in right ventricular end-diastolic assessed in mL and will be measured using serial echocardiograms and MRI scan. | Baseline, 12 months | 
| Change in Right Ventricular End-systolic Volume | Efficacy will be reported as the change in right ventricular end-systolic volume assessed in mm and will be measured using serial echocardiograms and MRI scan. | Baseline, 12 months | 
| Change in Tricuspid Regurgitation | Efficacy will be reported as the change tricuspid regurgitation assessed in m/s and will be measured using serial echocardiograms and MRI scan. | Baseline, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Incidence of Serious Adverse Events | Incidence of the following after the BDCPA / GLENN Procedure including: All-cause mortality; Cardiovascular mortality; Need for transplantation; Hospitalization for heart failure; Cardiovascular morbidity, including stroke or heart failure or sustained/symptomatic arrhythmias. | Up to 12 months | 
| Change in somatic growth velocity | Changes in somatic growth velocity will be evaluated by weight, height, head circumference over 12 months post-SPI. | Baseline, 12 months | 
| Change in Infant Toddler Quality of Life Survey (ITQOL) | Change in Infant Toddler Quality of Life Survey (ITQOL) is measured on a 9 scale with 47 items measuring child's overall health, physical abilities, overall growth and development, discomfort/pain, moods, and overall behavior. The total score ranges from 0 to 100 with the higher score indicating better quality of life. | Baseline, 12 months | 
| Incidence of mortality or need for transplantation | Incidence of mortality or need for transplantation after the Stage II BDCPA operation will be reported | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stem cells, pediatric