Summary

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

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 EncephalopathyBirth AsphyxiaBrain DiseasesAsphyxiaAsphyxia NeonatorumEpoetin AlfaErythropoietin

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., chest compressions, or positive pressure respiratory support including endotracheal, mask ventilation, or CPAP), or
  • pH < 7.00 in cord gas (arterial or venous) or in an infant gas (arterial or venous) obtained at < 60 minutes of age, or
  • 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

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 > 65.0%)
  • 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)

Locations

  • University of California, San Franciscoaccepting new patients
    San FranciscoCalifornia94158United States
  • Stanford Universityaccepting new patients
    Palo AltoCaliforniaUnited States

Lead Scientist

  • Yvonne Wu
    Dr. Yvonne Wu is a child neurologist and epidemiologist with expertise in newborn brain injury and cerebral palsy (CP). After obtaining a BS from Yale and an MD from Harvard Medical School, she completed her Child Neurology Residency training at University of California, San Francisco (UCSF) and obtained a MPH in Epidemiology at University of California, Berkeley.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT02811263
Phase
Phase 3
Study Type
Interventional
Last Updated