E.W. "Al" Thrasher
Status: Funded - Open
Neonatal Erythropoietin And Therapeutic Hypothermia Short-term Outcome Study (“NEAT O Study”)
Yvonne Wu, M.D., MPH
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) refers to brain dysfunction resulting from reduced blood and oxygen flow to a baby’s brain near the time of birth. Hypothermia, or cooling therapy, provides some protection to the brain. Nevertheless, half of infants with HIE who receive hypothermia have a bad outcome including death, cerebral palsy or intellectual disability.
GAP: Erythropoietin (Epo) is a drug that reduces brain injury and improves functional outcomes in animal models of HIE. Whether Epo + hypothermia is a safe and effective combination treatment for HIE in newborn infants is unknown.
HYPOTHESIS: We hypothesize that giving Epo + hypothermia to newborn infants with HIE is safe, and that early brain MRI findings will correlate with neurodevelopmental outcome at 12 months of age in infants who receive this experimental drug.
METHODS: In a randomized, double-blinded Phase II clinical trial, we will enroll 50 newborns who are undergoing hypothermia for HIE, and randomize the patients to receive either 5 doses of intravenous Epo 1000 U/kg, or normal saline placebo. We will then evaluate the infants’ brain MRI findings at 4-6 days of age, and their neurodevelopmental outcome at 12 months of age.
RESULTS: We found that among infants undergoing hypothermia for moderate/severe hypoxic-ischemic encephalopathy, multiple high doses of erythropoietin 1000 U/kg given intravenously over 7 days appeared safe, resulted in less MRI brain injury, and led to improved short-term motor outcomes.
IMPACT: This study has the potential to prevent childhood neurologic disabilities such as cerebral palsy, and to reduce associated societal costs. This study will allow us to move forward within a short time to design and perform a definitive phase III study to test this exciting new therapy for newborn brain injury.
Drug Therapy, Hypoxic Ischemic Encephalopathy, Neuro-Cognitive Development, Treatment, Human, Randomized Clinical Trial
University of California, San Francisco
California, Missouri, District of Columbia, Arkansas, Washington