Neonatal Erythropoietin And Therapeutic Hypothermia Outcomes in Newborn Brain Injury (NEATO)

Study Overview
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Brief Summary
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Hypoxic-ischemic encephalopathy (HIE), a condition of reduced blood and oxygen flow to a baby's brain near the time of birth, may cause death or neurologic disability. Cooling therapy (hypothermia) provides some protection, but about half of affected infants still have a poor outcome. This clinical trial will determine if the drug erythropoietin, given with hypothermia, is safe to use as a treatment that may further reduce the risk of neurologic deficits after HIE.

Detailed Description
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This phase I/II clinical trial is designed to demonstrate: The feasibility of recruiting, enrolling and following 50 patients with moderate to severe HIE at 5 sites, while meeting specified recruitment and follow-up target goals. The safety of high-dose Epo therapy in neonates with HIE with respect to systemic organ function and general growth parameters. The value of brain MRI/MRS performed at 4-7 days of age as a biomarker of motor function at 12 months of age.

Official Title
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Neonatal Erythropoietin And Therapeutic Hypothermia Outcomes Study

Conditions
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Hypoxic-ischemic Encephalopathy, Neonatal Encephalopathy, Birth Asphyxia

Intervention / Treatment
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* Drug: Erythropoietin
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newborns ≥ 36 weeks gestation, < 23 hours of age at time of consent, must meet all 3 Inclusion Criteria to be eligible for the study: Perinatal depression = at least one of the following: a) Apgar ≤5 at 10 min or b) required resuscitation (endotracheal or mask ventilation, or chest compressions) at 10 min or c) pH < 7.0 or base deficit ≥15 in cord, arterial, or venous blood obtained at <60 min of age; Moderate to severe encephalopathy = at least 3 of 6 modified Sarnat criteria present between 1-6 h of birth: a) reduced level of consciousness; b) decreased spontaneous activity; c) hypotonia; d) decreased suck; e) decreased Moro reflex; or f) respiratory distress including periodic breathing or apnea; and Hypothermia = passive or active cooling begun by 6 hours of age. Exclusion Criteria: Intrauterine growth restriction (BW <1800 g); Major congenital malformation; suspected genetic syndrome, metabolic disorder or TORCH infection; Head circumference < 2 SD for gestation; Infant for whom withdrawal of supportive care is being considered; or Anticipated inability to collect primary endpoint at 12 months of age.

Ages Eligible for Study
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Minimum Age: 30 Minutes
Maximum Age: 24 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 |
| --- | --- |
| Active Comparator: Erythropoietin<br>1000 U/kg/dose x 5 doses | Drug: Erythropoietin<br>* 1000 U/kg/dose IV x 5 doses<br>* Other names: Procrit;|
| Placebo Comparator: Normal saline<br> | Drug: Normal saline<br>* placebo: NS IV x 5 doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Markers of Organ Function | The investigators will monitor organ function and adverse events until hospital discharge from the neonatal intensive care unit | Participants will be followed for the duration of hospital stay, an expected average of 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alberta Infant Motor Scale (AIMS) | The AIMS consists of 58 items, including 4 positions: prone (21 items), supine (9 items), sitting (12 items), & standing (16 items). Each item is scored as 'observed' or 'not observed'. Total score range is 0-58, scored as percentile ranks after a raw score is obtained and plotted against age at testing, based on validated norms. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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erythropoietin, therapeutic hypothermia