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

Phase 2

Completed

Interventions: Biological: Infusion of autologous cord blood
Biological: Placebo

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Intervention cell recipients	Infusion of autologous cord blood	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
Placebo recipients	Placebo	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

Primary Outcome Measures

Name	Time	Method
Number of Participants With Bayley III Scores in All Three Domains > or Equal to 85	1 year	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.
Survival at One Year	1 year	Number of participants alive at one year.

Secondary Outcome Measures

Name	Time	Method
Mortality Rate	1 year	(Number of participants who died/total number of participants) x 100
Number of Subjects Who Require ECMO	During hospitalization, approximately 4-92 days	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.
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
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