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Summary

at San Francisco, California and other locations
study started
estimated completion:

Description

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.

Details

Neonatal hypoxic-ischemic encephalopathy (HIE) refers to brain injury resulting from reduced blood and oxygen flow to a baby's brain near the time of birth. HIE affects up to 12,000 newborns each year in the U.S. Half of affected infants have a bad outcome including death, cerebral palsy and cognitive impairment despite receiving hypothermia, the only available treatment. Erythropoietin (Epo) is a cytokine with remarkable neuroprotective and neuroregenerative effects demonstrated in animal models of neonatal brain injury. In a phase I trial of Epo + hypothermia, the investigators found that Epo 1000 U/Kg/dose best reproduced the pharmacokinetics of neuroprotective dosing in animal models. Long term outcomes were better than expected based on entry criteria and MRI findings. A phase II trial compared 50 cooled infants randomized to receive Epo or placebo. Infants treated with hypothermia + Epo had less brain injury on early MRI, and better 12-month motor development. The investigators hypothesize that Epo given to cooled infants with moderate/severe HIE will reduce the combined primary outcome of death or neurodevelopmental impairment from 49 to 33%. This is a randomized, double-blind, placebo-controlled trial of Epo therapy in 500 infants with HIE undergoing hypothermia. Specific aims are 1) To determine if 5 doses of Epo 1000 U/kg IV reduces the rate of death, motor or cognitive deficits at 2 years; 2) To assess safety of Epo by evaluating clinical toxicity; and 3) To determine whether Epo decreases the severity of neonatal brain injury as evidenced by early MRI and circulating biomarkers of brain injury. The investigators anticipate that Epo will confer improved 2-year neurodevelopmental outcome, will be safe, and will decrease brain injury severity as determined by early biomarkers.

Keywords

Neonatal Encephalopathy Birth Asphyxia Brain Diseases Asphyxia Asphyxia Neonatorum Epoetin Alfa

Eligibility

You can join if…

  • ≥ 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:
  • Apgar score < 5 at 10 minutes, or
  • Need for resuscitation at 10 minutes (i.e., endotracheal or mask ventilation, or chest compressions), or
  • pH < 7.00 in cord, arterial, or venous blood < 60 minutes of age
  • Base deficit ≥ 15 mmol/L in cord, arterial, or venous blood < 60 minutes of age
  • Moderate to severe encephalopathy (based on modified Sarnat exam) present between 1-6 hours after birth

You CAN'T join if...

  • 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%)
  • Parents with diminished capacity and autonomy
  • Infant is participating in another interventional study (note: does not include observational studies)

Locations

  • University of California, San Francisco accepting new patients
    San Francisco, California, 94158, United States
  • Stanford University accepting new patients
    Palo Alto, California, United States
  • Children's Hospital Los Angeles accepting new patients
    Los Angeles, California, United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT02811263
Phase
Phase 3
Lead Scientist
Yvonne Wu
Study Type
Interventional
Last Updated
September 13, 2017
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