High-dose Erythropoietin for Asphyxia and Encephalopathy

Last updated: January 4, 2023
Sponsor: University of California, San Francisco
Overall Status: Completed

Phase

3

Condition

Neurologic Disorders

Cerebral Palsy

Treatment

N/A

Clinical Study ID

NCT02811263
P0511976
  • Ages < 24
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • ≥ 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:
  1. Apgar score < 5 at 10 minutes, or
  2. Need for resuscitation at 10 minutes (i.e., chest compressions, or positivepressure respiratory support including endotracheal, mask ventilation, or CPAP),or
  3. pH < 7.00 in cord gas (arterial or venous) or in an infant gas (arterial orvenous) obtained at < 60 minutes of age, or
  4. 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 1-6hours after birth

Exclusion

Exclusion Criteria:

  • 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 multiplesurgeries (e.g., congenital viral infection, hydrops, complex congenital heartdisease, 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 studyduring 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)

Study Design

Total Participants: 500
Study Start date:
January 01, 2017
Estimated Completion Date:
April 30, 2022

Study Description

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.

Connect with a study center

  • University of Arkansas

    Little Rock, Arkansas
    United States

    Site Not Available

  • UC Davis

    Davis, California
    United States

    Site Not Available

  • Children's Hospital Los Angeles

    Los Angeles, California
    United States

    Site Not Available

  • Stanford University

    Palo Alto, California
    United States

    Site Not Available

  • University of California, San Francisco

    San Francisco, California 94158
    United States

    Site Not Available

  • Children's National Medical Center

    Washington, District of Columbia 20010
    United States

    Site Not Available

  • Children's National Medical Center

    Washington DC, District of Columbia 20010
    United States

    Site Not Available

  • Children's National Medical Center

    Washington, D.C., District of Columbia 20010
    United States

    Site Not Available

  • Northwestern University

    Chicago, Illinois
    United States

    Site Not Available

  • Indiana University

    Indianapolis, Indiana
    United States

    Site Not Available

  • Johns Hopkins University

    Baltimore, Maryland
    United States

    Site Not Available

  • Children's Hospitals and Clinics of Minnesota: Minneapolis

    Minneapolis, Minnesota
    United States

    Site Not Available

  • Children's Hospitals and Clinics of Minnesota: St. Paul

    Saint Paul, Minnesota
    United States

    Site Not Available

  • Childrens Hospital and Clinics of Minnesota

    St Paul, Minnesota
    United States

    Site Not Available

  • Washington University

    Saint Louis, Missouri 63110
    United States

    Site Not Available

  • Washington University

    St. Louis, Missouri 63110
    United States

    Site Not Available

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio
    United States

    Site Not Available

  • Good Samaritan Hospital

    Cincinnati, Ohio
    United States

    Site Not Available

  • Nationwide Children's Hospital

    Columbus, Ohio
    United States

    Site Not Available

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania
    United States

    Site Not Available

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania
    United States

    Site Not Available

  • Magee Women's Hospital of UPMC

    Pittsburgh, Pennsylvania
    United States

    Site Not Available

  • Vanderbilt University

    Nashville, Tennessee
    United States

    Site Not Available

  • UT Southwestern

    Dallas, Texas
    United States

    Site Not Available

  • Cook Children's Hospital

    Fort Worth, Texas
    United States

    Site Not Available

  • Children's Hospital of San Antonio

    San Antonio, Texas
    United States

    Site Not Available

  • Methodist Children's Hospital

    San Antonio, Texas
    United States

    Site Not Available

  • Primary Children's Hospital

    Salt Lake City, Utah
    United States

    Site Not Available

  • University of Utah

    Salt Lake City, Utah
    United States

    Site Not Available

  • Seattle Children's Hospital

    Seattle, Washington 98105
    United States

    Site Not Available

  • University of Washington Medical Center

    Seattle, Washington 98195
    United States

    Site Not Available

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