High-dose Erythropoietin for Asphyxia and Encephalopathy
Condition: Neonatal Encephalopathy; Birth Asphyxia
MeSH terms: Brain Diseases; Asphyxia Neonatorum; Asphyxia
Intervention: Normal saline placebo; Erythropoietin
Intervention description: Equal volume of normal saline to be used as placebo; Epogen drawn from commercially available single dose 4000U/mL vials
Intervention MeSH terms: Epoetin Alfa
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 500.0
Sex: All
Maximum age: 24 Hours
Healthy volunteers: No

Summary:

      Hypoxic-ischemic encephalopathy (HIE) occurs when a baby gets reduced blood flow and oxygen
      to the brain near the time of birth. This results in death or neurologic disabilities
      including cerebral palsy and cognitive impairment in up to half of affected infants. This
      clinical trial will determine if the drug erythropoietin (Epo) added to hypothermia (usual
      therapy) will improve outcomes for infants suffering from HIE.
    

Eligibility criteria:

        Inclusion Criteria:

          -  ≥ 36 weeks of gestational age

          -  Receiving active or passive whole body cooling/hypothermia since < 6 hours of age

          -  Perinatal depression based on at least one of the following:

               1. Apgar score < 5 at 10 minutes, or

               2. Need for resuscitation at 10 minutes (i.e., chest compressions, or positive
                  pressure respiratory support including endotracheal, mask ventilation, or CPAP),
                  or

               3. pH < 7.00 in cord gas (arterial or venous) or in an infant gas (arterial or
                  venous) obtained at < 60 minutes of age, or

               4. Base deficit ≥ 15 mmol/L in cord gas (arterial or venous) or in an infant gas
                  (arterial or venous) obtained at < 60 minutes of age

          -  Moderate to severe encephalopathy (based on modified Sarnat exam) present between 1-6
             hours after birth

        Exclusion Criteria:

          -  Study drug unlikely to be administered within 26 hours of birth

          -  Infant has living twin (or higher order multiple) who is also being cooled

          -  Birth weight < 1800 g (e.g., intrauterine growth restriction)

          -  Genetic or congenital condition that affects neurodevelopment or requires multiple
             surgeries (e.g., congenital viral infection, hydrops, complex congenital heart
             disease, severe dysmorphic features, etc.)

          -  Head circumference < 30 cm

          -  Redirection of care is being considered due to moribund condition

          -  Patient anticipated to be unavailable for evaluation at age 2

          -  Polycythemia (hematocrit > 65.0%)

          -  Parents/legal guardians with diminished capacity and autonomy

          -  Infant is participating or intends to participate in another interventional study
             during the birth hospitalization (note: does not include observational studies)

          -  Sentinel event and encephalopathy occurred only after birth

          -  Unable to consent in primary language of parent(s)