The CHILD Trial: Hypoplastic Left Heart Syndrome Study.

NCT03406884 — Phase 1, Completed, 25 participants, Joshua M Hare

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

Registry	NCT03406884, acronym CHILD
Status	Completed
Phase	Phase 1
Study type	Interventional; randomized, parallel, masking: none, treatment
Enrollment	25 (Actual)
Sponsor	Joshua M Hare (Other)
Conditions	Hypoplastic Left Heart Syndrome
Interventions	c-kit+ cells (Biological)
Dates	start 2019-10-16, primary completion 2024-07-01, completion 2024-07-01, first posted 2018-01-23, last updated 2026-01-23
Locations	4 sites in United States

-Summary

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 Bidirectional Cavopulmonary Anastomosis (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.

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+Arms and interventions

Arm	Type	Interventions	Description
Open label C-kit+ cells Group A	Experimental	Biological: c-kit+ cells	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.
C-kit+ cells Group B	Active comparator	Biological: c-kit+ cells	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.
No Intervention Group	No intervention		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.

c-kit+ cells (Biological), also known as Autologous c-kit-positive cells (c-kit+ cells): 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.

+Outcome measures

Primary outcomes

Number of Incidence of Treatment Related Major Adverse Cardiac Events [30 days]: 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.
Number of C-kit+ Products [Day 1]: Feasibility will be reported as the number of c-kit+ products that can be manufactured and delivered to subjects
Number of Participants Completing Magnetic Resonance Imaging (MRI) [Baseline, 6 Months, 12 months]: Feasibility will be reported as the number of participants that complete the baseline, 6-months, and 12-months follow up MRI.
Change in Right Ventricular Function (RVEF) [Baseline, 6 Months, 12 months]: 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.
Change in Right Ventricular End-diastolic Volume (RVEDV) [Baseline, 6 months, 12 months]: Efficacy will be reported as the change in right ventricular end-diastolic assessed in milliliters per square meter and will be measured using serial echocardiograms and MRI scan.
Change in Right Ventricular End-systolic Volume (RVESV) [Baseline, 6 months, 12 months]: Efficacy will be reported as the change in right ventricular end-systolic volume assessed in milliliters per square meter and will be measured using serial echocardiograms and MRI scan.
Change in Tricuspid Regurgitation [Baseline, 6 months, 12 months]: Efficacy will be reported as the change tricuspid regurgitation assessed as a percentage and will be measured using serial echocardiograms and MRI scan.

Secondary outcomes

Number of Incidence of Serious Adverse Events [Up to 12 months]: 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.
Change in Somatic Growth Velocity - Length (cm) [Baseline, 6 months, 12 months]: Changes in somatic growth velocity will be evaluated by length (cm) over 12 months post study product injection.
Change in Somatic Growth Velocity - Weight (kg) [Baseline, 6 months, 12 months]: Changes in somatic growth velocity will be evaluated by weight (kg) over 12 months post study product injection.
Change in Somatic Growth Velocity - Head Circumference (cm) [Baseline, 6 months, 12 months]: Changes in somatic growth velocity will be evaluated by head circumference (cm) over 12 months post study product injection.
Change in Infant Toddler Quality of Life Survey (ITQOL) - Overall Health [Baseline, 12 months]: The Infant Toddler Quality of Life Survey (ITQOL) is a validated 47-item parent-reported questionnaire assessing multiple domains of child health, including overall health, physical abilities, growth and development, discomfort/pain, mood, and behavior. Domain scores are transformed to a 0-100 scale, where 0 reflects the poorest health-related quality of life and 100 reflects the best. Higher scores indicate better quality of life.
Incidence of Mortality or Need for Transplantation [Up to 12 months]: Incidence of mortality or need for transplantation after the Stage II BDCPA operation will be reported

+Eligibility

Sex: All, ages: 1 Day to 21 Days

Inclusion Criteria:

* For inclusion in the study, subjects must meet all of the inclusion criteria:

  1. Subjects with hypoplastic left heart syndrome (HLHS) (all types) requiring Stage I Norwood operation.

     Exclusion Criteria:
* Candidates will be excluded from the study if any of the following conditions are met:

  1. Subjects undergoing the Stage I Norwood operation who do not have HLHS.
  2. Subjects requiring mechanical circulatory support immediately prior to Stage II BDCPA operation (within 5 days).
  3. Parent or guardian unwilling or unable to comply with necessary follow-up(s).
  4. Mother is serum positive for HIV 1/2, hepatitis B surface antigen or viremic hepatitis C and Treponema pallidum.
  5. Subjects who are unsuitable for inclusion in the study in the opinion of the investigator(s).

+Posted results

Participant flow

Milestone	Open Label C-kit+ Cells Group A	C-kit+ Cells Group B	No Intervention Group
Started	9	8	8
Completed	9	8	8
Not completed	0	0	0

Outcome results

Number of Incidence of Treatment Related Major Adverse Cardiac Events (Primary), Number, Events: Open Label C-kit+ Cells Group A 1; C-kit+ Cells Group B 0; No Intervention Group 6
Number of C-kit+ Products (Primary), Number, Products: Open Label C-kit+ Cells Group A 9; C-kit+ Cells Group B 7; No Intervention Group 0
Number of Participants Completing Magnetic Resonance Imaging (MRI) (Primary), Count of participants, Participants: Open Label C-kit+ Cells Group A 9; C-kit+ Cells Group B 7; No Intervention Group 7
Change in Right Ventricular Function (RVEF) (Primary), Mean, percentage: Open Label C-kit+ Cells Group A 49.33 +/- 4.44; C-kit+ Cells Group B 55 +/- 7.19; No Intervention Group 45.4 +/- 10.25
Change in Right Ventricular End-diastolic Volume (RVEDV) (Primary), Mean, milliliters per square meter: Open Label C-kit+ Cells Group A 112.57 +/- 20.75; C-kit+ Cells Group B 119.1 +/- 35.08; No Intervention Group 123.98 +/- 18.92
Change in Right Ventricular End-systolic Volume (RVESV) (Primary), Mean, milliliters per square meter: Open Label C-kit+ Cells Group A 57.43 +/- 13.22; C-kit+ Cells Group B 55.53 +/- 23.87; No Intervention Group 68.66 +/- 22.04
Change in Tricuspid Regurgitation (Primary), Mean, percentage: Open Label C-kit+ Cells Group A 8.28 +/- 5.21; C-kit+ Cells Group B 5 +/- 0; No Intervention Group 5 +/- 0
Number of Incidence of Serious Adverse Events (Secondary), Number, Events: Open Label C-kit+ Cells Group A 1; C-kit+ Cells Group B 0; No Intervention Group 6
Change in Somatic Growth Velocity - Length (cm) (Secondary), Mean, centimeters: Open Label C-kit+ Cells Group A 60.33 +/- 3.82; C-kit+ Cells Group B 59.5 +/- 3.28; No Intervention Group 60.07 +/- 4.94
Change in Somatic Growth Velocity - Weight (kg) (Secondary), Mean, kilograms: Open Label C-kit+ Cells Group A 5.7 +/- 0.66; C-kit+ Cells Group B 5.6 +/- 0.74; No Intervention Group 5.65 +/- 0.69
Change in Somatic Growth Velocity - Head Circumference (cm) (Secondary), Mean, centimeters: Open Label C-kit+ Cells Group A 38.51 +/- 3.01; C-kit+ Cells Group B 39.58 +/- 2.69; No Intervention Group 38.33 +/- 3.18
Change in Infant Toddler Quality of Life Survey (ITQOL) - Overall Health (Secondary), Mean, score on a scale: Open Label C-kit+ Cells Group A 86 +/- 16.36; C-kit+ Cells Group B 62.14 +/- 24.64; No Intervention Group 77.86 +/- 12.2
Incidence of Mortality or Need for Transplantation (Secondary), Count of participants, Participants: Open Label C-kit+ Cells Group A 0; C-kit+ Cells Group B 0; No Intervention Group 3

Adverse events

Time frame: 1 year

Arm	Deaths	Serious adverse events	Other adverse events
Open Label C-kit+ Cells Group A	0/9 (0.0%)	8/9 (88.9%)	5/9 (55.6%)
C-kit+ Cells Group B	0/8 (0.0%)	4/8 (50.0%)	6/8 (75.0%)
No Intervention Group	1/8 (12.5%)	4/8 (50.0%)	6/8 (75.0%)

Serious adverse events by term

Term	Organ system	Open Label C-kit+ Cells Group A	C-kit+ Cells Group B	No Intervention Group
Acute right ventricular failure	Cardiac disorders	0/9	0/8	1/8
Atrial flutter	Cardiac disorders	0/9	1/8	0/8
Atrioventricular block complete	Cardiac disorders	0/9	0/8	1/8
Bradycardia	Cardiac disorders	1/9	1/8	2/8
Cardiac arrest	Cardiac disorders	1/9	0/8	2/8
Cardiac failure	Cardiac disorders	1/9	1/8	1/8
Cardiopulmonary failure	Cardiac disorders	0/9	0/8	1/8
Right ventricular dysfunction	Cardiac disorders	0/9	0/8	1/8
Supraventricular tachycardia	Cardiac disorders	1/9	0/8	0/8
Tachyarrhythmia	Cardiac disorders	0/9	0/8	1/8
Tricuspid valve incompetence	Cardiac disorders	2/9	0/8	1/8
Coarctation of the aorta	Congenital, familial and genetic disorders	1/9	0/8	1/8
Dysphagia	Gastrointestinal disorders	1/9	0/8	0/8
Gastrooesophageal reflux disease	Gastrointestinal disorders	1/9	0/8	0/8
Haematochezia	Gastrointestinal disorders	3/9	0/8	0/8
Necrotising colitis	Gastrointestinal disorders	0/9	0/8	1/8
Vomiting	Gastrointestinal disorders	1/9	0/8	0/8
Crying	General disorders	1/9	0/8	0/8
Vascular stent thrombosis	General disorders	0/9	0/8	1/8
Withdrawal syndrome	General disorders	1/9	0/8	0/8
Bacterial sepsis	Infections and infestations	0/9	0/8	1/8
Bronchiolitis	Infections and infestations	1/9	0/8	0/8
COVID-19	Infections and infestations	1/9	1/8	1/8
Infection	Infections and infestations	1/9	1/8	1/8
Mediastinitis	Infections and infestations	1/9	0/8	0/8
Otitis media	Infections and infestations	1/9	0/8	0/8
Parainfluenzae virus infection	Infections and infestations	0/9	0/8	1/8
Pneumonia	Infections and infestations	1/9	0/8	0/8
Sepsis	Infections and infestations	0/9	0/8	2/8
Urinary tract infection	Infections and infestations	1/9	0/8	1/8
Viral infection	Infections and infestations	2/9	0/8	0/8
Viral myocarditis	Infections and infestations	0/9	0/8	1/8
upper respiratory infection	Infections and infestations	1/9	0/8	0/8
Aortic restenosis	Injury, poisoning and procedural complications	2/9	0/8	0/8
Cardiac function disturbance postoperative	Injury, poisoning and procedural complications	0/9	0/8	1/8
Diaphragmatic injury	Injury, poisoning and procedural complications	1/9	0/8	0/8
Shunt stenosis	Injury, poisoning and procedural complications	1/9	0/8	1/8
Acidosis	Metabolism and nutrition disorders	0/9	0/8	1/8
Failure to thrive	Metabolism and nutrition disorders	1/9	0/8	0/8
Feeding intolerance	Metabolism and nutrition disorders	0/9	2/8	1/8
Hyperkalaemia	Metabolism and nutrition disorders	0/9	0/8	1/8
Cerebrovascular accident	Nervous system disorders	1/9	0/8	0/8
Infant irritability	Nervous system disorders	0/9	1/8	0/8
Seizure	Nervous system disorders	1/9	0/8	1/8
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	1/9	0/8	0/8
Chylothorax	Respiratory, thoracic and mediastinal disorders	1/9	0/8	0/8
Diaphragmatic paralysis	Respiratory, thoracic and mediastinal disorders	1/9	0/8	0/8
Dyspnea	Respiratory, thoracic and mediastinal disorders	0/9	0/8	1/8
Haemothorax	Respiratory, thoracic and mediastinal disorders	1/9	0/8	0/8
Hypoxia	Respiratory, thoracic and mediastinal disorders	1/9	2/8	3/8
Pneumothorax	Respiratory, thoracic and mediastinal disorders	0/9	0/8	1/8
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	0/9	0/8	1/8
Pulmonary vein stenosis	Respiratory, thoracic and mediastinal disorders	1/9	0/8	0/8
Respiratory failure	Respiratory, thoracic and mediastinal disorders	1/9	1/8	1/8
Collateral circulation	Vascular disorders	0/9	0/8	1/8
Deep vein thrombosis	Vascular disorders	0/9	1/8	1/8
Hypotension	Vascular disorders	0/9	0/8	1/8
Jugular vein thrombosis	Vascular disorders	0/9	0/8	1/8
Peripheral artery occlusion	Vascular disorders	0/9	1/8	0/8
Vena cava stenosis	Vascular disorders	0/9	1/8	1/8

1 more terms not shown.

Other adverse events by term

Term	Organ system	Open Label C-kit+ Cells Group A	C-kit+ Cells Group B	No Intervention Group
Bradycardia	Cardiac disorders	0/9	0/8	1/8
Tricuspid valve incompetence	Cardiac disorders	0/9	1/8	0/8
Haematochezia	Gastrointestinal disorders	0/9	1/8	0/8
Necrotising colitis	Gastrointestinal disorders	0/9	1/8	1/8
Vomiting	Gastrointestinal disorders	0/9	1/8	0/8
Device embolisation	General disorders	0/9	0/8	1/8
Drug withdrawal syndrome	General disorders	0/9	0/8	1/8
Granuloma	General disorders	0/9	0/8	1/8
Pyrexia	General disorders	1/9	0/8	0/8
Bacteraemia	Infections and infestations	0/9	0/8	1/8
COVID-19	Infections and infestations	0/9	2/8	0/8
Fungaemia	Infections and infestations	0/9	0/8	1/8
Pneumonia	Infections and infestations	1/9	0/8	2/8
Pseudomonas infection	Infections and infestations	1/9	0/8	0/8
Urinary tract infection	Infections and infestations	1/9	0/8	0/8
Viral infection	Infections and infestations	1/9	0/8	0/8
Accidental exposure to product by child	Injury, poisoning and procedural complications	1/9	0/8	0/8
Fall	Injury, poisoning and procedural complications	0/9	1/8	0/8
Femur Fracture	Injury, poisoning and procedural complications	0/9	0/8	1/8
Injury	Injury, poisoning and procedural complications	1/9	0/8	0/8
Medication Error	Injury, poisoning and procedural complications	0/9	1/8	0/8
Spinal Fracture	Injury, poisoning and procedural complications	0/9	0/8	1/8
Subdural Haematoma	Injury, poisoning and procedural complications	0/9	0/8	1/8
Dehydration	Metabolism and nutrition disorders	0/9	1/8	0/8
Failure to thrive	Metabolism and nutrition disorders	0/9	0/8	1/8
Hypocalcaemia	Metabolism and nutrition disorders	0/9	0/8	1/8
Hypokalaemia	Metabolism and nutrition disorders	0/9	1/8	1/8
Hypomagnesaemia	Metabolism and nutrition disorders	0/9	0/8	1/8
Osteopenia	Musculoskeletal and connective tissue disorders	0/9	0/8	1/8
Presyncope	Nervous system disorders	0/9	1/8	0/8
Seizure	Nervous system disorders	0/9	1/8	1/8
Bronchomalacia	Respiratory, thoracic and mediastinal disorders	0/9	1/8	0/8
Chylothorax	Respiratory, thoracic and mediastinal disorders	1/9	1/8	0/8
Hypoxia	Respiratory, thoracic and mediastinal disorders	1/9	1/8	1/8
Pleural effusion	Respiratory, thoracic and mediastinal disorders	0/9	0/8	1/8
Pulmonary artery occlusion	Respiratory, thoracic and mediastinal disorders	0/9	0/8	1/8
Stridor	Respiratory, thoracic and mediastinal disorders	0/9	0/8	1/8
Skin Disorder	Skin and subcutaneous tissue disorders	0/9	0/8	1/8
Labile blood pressure	Vascular disorders	0/9	0/8	1/8

+Locations (4)

Facility	City	Country
Emory University Children's Healthcare of Atlanta - Egleston Campus	Atlanta, Georgia	United States
Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago, Illinois	United States
University of Maryland - Division of Cardiac Surgery	Baltimore, Maryland	United States
Michigan Medicine Congenital Heart Center/C.S. Mott Children's Hospital	Ann Arbor, Michigan	United States

+Publications

Results publication: Kaushal S, Hare JM, Mahle WT, Khan A, Ohye RG, Slesnick TC, Chai PJ, Shashidharan S, Robinson JD, Jone PN, Doman T, Si MS, Lu JC, Bacallao K, Nettina AE, Lamazares R, Saltzman RG, Simpson LM, Li R, Bettencourt JE, Mansoor K, Davis BR, Deatrick KB, Yang J, Mishra R, Everett AD, Lai D, Davis ME. Phase I Randomized Study of Cardiac Stem Cells in Patients With Hypoplastic Left Heart Syndrome: The CHILD Trial. JACC Heart Fail. 2026 Jan;14(1):102723. doi: 10.1016/j.jchf.2025.102723. Epub 2025 Nov 19. PMID 41258851
Results publication: Kaushal S, Hare JM, Shah AM, Pietris NP, Bettencourt JL, Piller LB, Khan A, Snyder A, Boyd RM, Abdullah M, Mishra R, Sharma S, Slesnick TC, Si MS, Chai PJ, Davis BR, Lai D, Davis ME, Mahle WT. Autologous Cardiac Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome (CHILD Study). Pediatr Cardiol. 2022 Oct;43(7):1481-1493. doi: 10.1007/s00246-022-02872-6. Epub 2022 Apr 8. PMID 35394149
Results publication: Ali MK, Ichimura K, Spiekerkoetter E. Promising therapeutic approaches in pulmonary arterial hypertension. Curr Opin Pharmacol. 2021 Aug;59:127-139. doi: 10.1016/j.coph.2021.05.003. Epub 2021 Jun 30. PMID 34217109

+Study documents

Study Protocol and Statistical Analysis Plan (PDF, 2021-03-23)

+Investigators

William Mahle, MD, Principal investigator, Emory University
Kristopher Deatrick, MD, Principal investigator, University of Maryland
Richard Ohye, MD, Principal investigator, Michigan Medicine Congenital Heart Center/C.S. Mott Children's Hospital