A Multi-site Study of Autologous Cord Blood Cells for Hypoxic Ischemic Encephalopathy

Study Overview
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Brief Summary
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This study will test the safety and efficacy of an infusion of a baby's own (autologous) umbilical cord blood as compared with placebo in babies born with history and signs of hypoxic-ischemic brain injury.

Detailed Description
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The purpose of this phase II study is to assess the safety and efficacy of up to two intravenous infusions of autologous volume and red blood cell reduced nucleated umbilical cord blood cells as compared with placebo in neonates with neonatal encephalopathy undergoing hypothermia treatment. Efficacy will be estimated by one year survival and score on Bayley III scores in all three domains equal to or greater than 85. This will be a randomized, double-blind, placebo controlled multi-site trial of up to 160 infants who qualify for cooling.

Official Title
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A Phase II Multi-site Study of Autologous Cord Blood Cells for Hypoxic (HIE)

Conditions
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Moderate or Severe Hypoxic-ischemic Encephalopathy in Newborns

Intervention / Treatment
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* Biological: Infusion of autologous cord blood
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: NICHD Neonatal Research Network Hypothermia Trial inclusion criteria Mothers must have consented or given verbal assent for cord blood collection at delivery, and cord blood must be available for volume and red blood cell reduction before 45 hours of age The infant must be able to receive at least one dose of autologous cord blood before 48 hours of age All infants must have signs of encephalopathy within 6 hours of age Exclusion Criteria: Major congenital or chromosomal abnormalities Severe growth restriction (birth weight <1800 g) Opinion by attending neonatologist that the study may interfere with treatment or safety of subject Moribund neonates for whom no further treatment is planned Infants born to mothers are known to be HIV, Hepatitis B, Hepatitis C or who have active syphilis or CMV infection in pregnancy Infants suspected of overwhelming sepsis ECMO initiated or likely in the first 48 hours of life

Ages Eligible for Study
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Maximum Age: 6 Hours

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention cell recipients<br>Experimental: infusions: infants with moderate to severe hypoxic ischemic encephalopathy, begin cooling, and have autologous nucleated cord blood cells available for infusion will receive up to two infusions. Outcomes will be measured at 22-26 months by neurodevelopment assessment | Biological: Infusion of autologous cord blood<br>* Infants who meet study enrollment criteria will receive up to 2 infusions of their own volume reduced cord blood cells. The number of doses will be determined by the amount of available cord blood cells.<br>|
| Placebo Comparator: Placebo recipients<br>Control: infants with moderate to severe hypoxic ischemic encephalopathy, begin cooling, and have cord blood available for infusion will receive placebo (a mix of autologous cord blood red blood cells and plasma) infusions. Outcomes will be measured at 22-26 months by neurodevelopment assessment | Biological: Placebo<br>* Infants who meet study enrollment criteria will receive up to 2 placebo infusions composed of an equivalent volume (volume of product that would have been administered if the infant randomized to the intervention arm) of packed red blood cells (PRBCs) from the red cell compartment of the separated cord blood unit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival at One Year | Number of participants alive at one year. | 1 year | 
| Number of Participants With Bayley III Scores in All Three Domains > or Equal to 85 | The Bayley is a standardized, norm-referenced measure that assesses development in Cognitive, Language and Motor domains. Composite standard scores can be derived that have a mean of 100 and a standard deviation of 15. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality Rate | (Number of participants who died/total number of participants) x 100 | 1 year | 
| Number of Subjects Who Experience Seizures |  | During hospitalization, approximately 4-92 days | 
| Number of Subjects Who Require iNO (Inhaled Nitric Oxide) Use |  | During hospitalization, approximately 4-92 days | 
| Number of Subjects Who Require ECMO | ECMO (extracorporeal membrane oxygenation) is a technique of providing prolonged cardiac and respiratory support to persons whose heart and lungs are unable to provide an adequate amount of gas exchange or perfusion to sustain life. | During hospitalization, approximately 4-92 days | 
| Number of Subjects Who Require Gastrostomy Tube (G-tube) Feeding |  | During hospitalization, approximately 4-92 days | 
| Number of Subjects Who Are Discharged on Anti-epileptic Medication |  | At hospital discharge, approximately 4-92 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autologous cord blood cells, Hypoxic-ischemic encephalopathy, newborn infants