Efficacy of Erythropoietin to Improve Survival and Neurological Outcome in Hypoxic Ischemic Encephalopathy

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy of high dose Erythropoietin to improve survival and neurologic outcome in asphyxiated term newborn undergoing cooling.

Detailed Description
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Hypoxic-ischemic encephalopathy remains the main cause of death or long term neurologic impairments in neonates. Yet, therapies for birth asphyxia are currently limited. Hypothermia when applied within 6 hours after birth demonstrate partial improvement in outcome of newborns specially those with moderate form. Erythropoietin and its receptors are upregulated after brain injury in ischemic conditions. Systemically administered erythropoietin is neuroprotective in animal models of birth asphyxia. To date, one study demonstrate improvement neurologic outcome in asphyxiated term newborn under erythropoietin treatment but no reports evaluating beneficial of erythropoietin associated with cooling. This is a large randomised controlled trial to evaluate the efficacy of high dose erythropoietin on outcome at two years of asphyxiated term newborns undergoing cooling.

Official Title
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Phase III Study of Efficacy of High Dose Erythropoietin to Prevent Hypoxic-ischemic Encephalopathy Sequelae in Term Newborn

Conditions
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Hypoxic Ischemic Encephalopathy

Intervention / Treatment
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* Drug: erythropoietin Beta
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Term or near-term newborn (> = 36 weeks gestational age) Moderate to severe encephalopathy undergoing moderate controlled hypothermia started within 6 hours after delivery : rectal or esophageal temperature maintained at 33.5 ° C + / - 0.5 ° C before H6 Beneficiary of social security plan Informed consent parental authority Exclusion Criteria: Impossibility of getting controlled hypothermia before H6 Infant older than 12 hours of age Chromosomal or significant congenital abnormality Predictable surgery in the first 3 days of life Uncontrolled collapse Haemorrhagic syndrome unchecked Head trauma with or without skull fracture

Ages Eligible for Study
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Maximum Age: 12 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Erythropoietin beta<br>1000 to 1500 U/kg/dose X 3 every 24 hours | Drug: erythropoietin Beta<br>* erythropoietin intravenous injection (5000 U/ 0.3 ml)1000 to 1500 U/kg/dose X 3 given every 24 hours with the first dose within 12 hours of delivery<br>|
| Placebo Comparator: Placebo<br>0.2 ml saline solution X 3 given every 24 hours | Drug: Placebo<br> <br> * Other names: 0.2 ml saline solution X 3 given every 24 hours with the first dose within 12 hours of delivery;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival without neurologic sequelae |  | at 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rates | number of dead patients | Within 24 months | 
| Rate of moderate and severe sequelae | Mental Developmental index (Brunet Lezine Test), motor, visual and hearing impairment | at 24 months | 
| Aspect of brain lesions on MRI | Brain MRI performed between day 6 and day 12 after birth | at day 6 and day 12 after birth | 
| Tolerance of treatment |  | at 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoxic Ischemic Encephalopathy, Term neonate, Neuroprotection, erythropoietin