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

Phase 1

Completed

Conditions: Birth Asphyxia
Hypoxic-ischemic Encephalopathy
Neonatal Encephalopathy

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Erythropoietin	Erythropoietin	1000 U/kg/dose x 5 doses
Normal saline	Normal saline	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Alberta Infant Motor Scale (AIMS)	12 months	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.

Locations (7): Washington University
🇺🇸
Saint Louis, Missouri, United States
Arkansas Children's Hospital Research Institute
🇺🇸
Little Rock, Arkansas, United States
Stanford University
🇺🇸
Palo Alto, California, United States
UCSF
🇺🇸
San Francisco, California, United States
Kaiser Permanente, Santa Clara
🇺🇸
Santa Clara, California, United States
Seattle Children's Hospital
🇺🇸
Seattle, Washington, United States
Children's National Medical Center
🇺🇸
Washington, District of Columbia, United States