Clinical Trial: High-dose Erythropoietin for Asphyxia and Encephalopathy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: High-dose Erythropoietin for Asphyxia and Encephalopathy

Brief 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.

Detailed Summary: 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.
Sponsor: University of California, San Francisco

Current Primary Outcome: Death or moderate/severe neurodevelopmental impairment [ Time Frame: Prior to final outcome assessment at 22-26 months of age ]

Neurodevelopmental impairment defined as any of the following: a) Gross Motor Function Scale (GMFCS) level ≥ 2, or b) GMFCS = 1 and cerebral palsy (CP) (any type), or c) GMFCS = 0 or 0.5 and quadriparetic CP, or d) Bayley III Cognitive Score < 85


Original Primary Outcome:

  • Death (component of primary outcome) [ Time Frame: Prior to final outcome assessment at 22-26 months of age ]
  • Cerebral palsy (component of primary outcome) [ Time Frame: 22-26 months of age ]
    Based on standardized neurologic exam (Kuban K)
  • Gross Motor Function Classification Scale (GMFCS) (component of primary outcome) [ Time Frame: 22-26 months ]
    Palisano (0 = normal, 1-5 = abnormal)
  • Bayley III cognitive score (component of primary outcome [ Time Frame: 22-26 months ]
    Categories of abnormality: severe ≤ 70; moderate > 70 and ≤ 85; mild > 85 and ≤ 90; normal > 90)
  • Primary Outcome = death or moderate to severe neurodevelopmental impairment [ Time Frame: 22-26 months ]
    1) Death or 2) cerebral palsy or 3) GMFCS > 0 or 4) Bayley III cognitive score ≤ 85


Current Secondary Outcome:

  • Presence and type of cerebral palsy (CP) determined using a standardized neurologic examination [ Time Frame: 22-26 months ]
    Neurologic diagnoses: no CP, diparetic CP, hemiparetic CP, quadriparetic CP
  • Level of gross motor function determined using the GMFCS [ Time Frame: 22-26 months ]
  • Bayley III cognitive and language scores [ Time Frame: 22-26 months ]
  • Presence of epilepsy [ Time Frame: Prior to 22-26 months ]
    ≥ 2 afebrile, unprovoked seizures
  • Behavioral abnormalities determined by the externalizing score of the Child Behavior Checklist [ Time Frame: 22-26 months ]


Original Secondary Outcome:

  • Bayley III language score [ Time Frame: 22-26 months of age ]
    Continuous score
  • Epilepsy [ Time Frame: 22-26 months ]
    prescribed anticonvulsant medications to prevent seizures
  • Child Behavior Checklist (CBC-L) [ Time Frame: 22-26 months ]
    continuous score
  • Weight [ Time Frame: 22-26 months ]
    in kilograms
  • Height [ Time Frame: 22-26 months ]
    in centimeters
  • Head circumference [ Time Frame: 22-26 months ]
    in centimeters
  • Cortical visual impairment [ Time Frame: 22-26 months ]
    Diagnosed by an opthalmologist
  • Hearing impairment requiring hearing aids [ Time Frame: 22-26 months ]
    Prescribed hearing aids


Information By: University of California, San Francisco

Dates:
Date Received: June 17, 2016
Date Started: January 2017
Date Completion: September 2022
Last Updated: May 22, 2017
Last Verified: May 2017