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

Neonatal Erythropoietin And Therapeutic Hypothermia Outcomes Study

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.

This phase I/II clinical trial is designed to demonstrate:

1. 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.
2. The safety of high-dose Epo therapy in neonates with HIE with respect to systemic organ function and general growth parameters.
3. The value of brain MRI/MRS performed at 4-7 days of age as a biomarker of motor function at 12 months of age.

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:

  1. 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;
  2. 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
  3. 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.