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High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2016 by University of California, San Francisco
Sponsor:
Collaborators:
University of Washington
Mednax Center for Research, Education and Quality
University of Utah
Children's Research Institute
University of Minnesota - Clinical and Translational Science Institute
University of Texas
Washington University School of Medicine
Indiana University
Stanford University
University of Pittsburgh
University of California, Davis
Northwestern
Children's Hospital Los Angeles
Nationwide Children's Hospital
Johns Hopkins University
Boston University
University of New Mexico
University of Chicago
University of North Carolina
Information provided by (Responsible Party):
Yvonne Wu, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT02811263
First received: June 17, 2016
Last updated: June 20, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Neonatal Encephalopathy
Birth Asphyxia
Drug: Normal saline placebo
Drug: erythropoietin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: High-dose Erythropoietin for Asphyxia and Encephalopathy

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Death (component of primary outcome) [ Time Frame: Prior to final outcome assessment at 22-26 months of age ] [ Designated as safety issue: Yes ]
  • Cerebral palsy (component of primary outcome) [ Time Frame: 22-26 months of age ] [ Designated as safety issue: Yes ]
    Based on standardized neurologic exam (Kuban K)

  • Gross Motor Function Classification Scale (GMFCS) (component of primary outcome) [ Time Frame: 22-26 months ] [ Designated as safety issue: Yes ]
    Palisano (0 = normal, 1-5 = abnormal)

  • Bayley III cognitive score (component of primary outcome [ Time Frame: 22-26 months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    1) Death or 2) cerebral palsy or 3) GMFCS > 0 or 4) Bayley III cognitive score ≤ 85


Secondary Outcome Measures:
  • Bayley III language score [ Time Frame: 22-26 months of age ] [ Designated as safety issue: No ]
    Continuous score

  • Epilepsy [ Time Frame: 22-26 months ] [ Designated as safety issue: No ]
    prescribed anticonvulsant medications to prevent seizures

  • Child Behavior Checklist (CBC-L) [ Time Frame: 22-26 months ] [ Designated as safety issue: No ]
    continuous score

  • Weight [ Time Frame: 22-26 months ] [ Designated as safety issue: No ]
    in kilograms

  • Height [ Time Frame: 22-26 months ] [ Designated as safety issue: No ]
    in centimeters

  • Head circumference [ Time Frame: 22-26 months ] [ Designated as safety issue: No ]
    in centimeters

  • Cortical visual impairment [ Time Frame: 22-26 months ] [ Designated as safety issue: No ]
    Diagnosed by an opthalmologist

  • Hearing impairment requiring hearing aids [ Time Frame: 22-26 months ] [ Designated as safety issue: No ]
    Prescribed hearing aids


Estimated Enrollment: 500
Study Start Date: September 2016
Estimated Study Completion Date: September 2022
Estimated Primary Completion Date: January 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Erythropoietin
Erythropoietin 1000 U/kg IV, at 1, 2, 3, 4 and 7 days of age (i.e., 5 doses)
Drug: erythropoietin
Epogen drawn from commercially available single dose 4000U/mL vials
Other Name: Epogen
Placebo Comparator: Placebo
Normal saline IV (equal volume), at 1, 2, 3, 4 and 7 days of age
Drug: Normal saline placebo
Equal volume of normal saline to be used as placebo
Other Name: NS

Detailed 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. Secific 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.
  Eligibility

Ages Eligible for Study:   up to 24 Hours   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥ 36 weeks of gestation
  • Started passive or active hypothermia by 6 hours of age
  • Perinatal depression = at least one of the following:

    1. Apgar ≤ 5 at 10 minutes of age
    2. Endotracheal/mask ventilation or chest compressions at 10 min of age
    3. pH < 7.0 or base deficit ≥ 15 mEq/L in cord, arterial, or venous blood obtained at < 60 minutes of age
  • Moderate or severe encephalopathy (based on modified Sarnat exam)

Exclusion Criteria:

  • Multiple births
  • Intrauterine growth restriction (birth weight <1800 g)
  • Genetic or congenital condition that is known to affect neurodevelopment
  • Head circumference < 30 cm;
  • Withdrawal of care is being considered due to moribund condition;
  • Patient will be unavailable for exam at age 2
  • Polycythemia (hematocrit > 65%)
  • Parents with diminished capacity and autonomy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02811263

Contacts
Contact: Yvonne Wu, MD MPH wuy@ucsf.edu
Contact: Fernando Gonzalez, MD Fernando.Gonzalez@ucsf.edu

Locations
United States, California
UC Davis Not yet recruiting
Davis, California, United States
Contact: Ian Griffin, MD       ijgriffin@ucdavis.edu   
Children's Hospital Los Angeles Not yet recruiting
Los Angeles, California, United States
Contact: Tai-Wei Wu, MD       twu@chla.usc.edu   
Stanford University Not yet recruiting
Palo Alto, California, United States
Contact: Krisa Van Meurs, MD         
Contact: Elizabeth Ball, RN    (650) 725-8342    mbball@stanford.edu   
United States, District of Columbia
Children's National Medical Center Not yet recruiting
Washington DC, District of Columbia, United States, 20010
Contact: Taeun Chang, MD    202-259-0170    tchang@cnmc.org   
Principal Investigator: Taeun Chang, MD         
Sub-Investigator: An Massaro, MD         
United States, Illinois
Northwestern University Not yet recruiting
Chicago, Illinois, United States
Contact: Janine Yasmin Khan, MD       J-khan@northwestern.edu   
United States, Indiana
University of Indiana Not yet recruiting
Indianapolis, Indiana, United States
Contact: Ulrike Mietzsch, MD       umietzsc@iu.edu   
Sub-Investigator: Mandy Harris, MD         
United States, Maryland
Johns Hopkins University Not yet recruiting
Baltimore, Maryland, United States
Contact: Maureen Gilmore, MD       mgilmor1@jhmi.edu   
United States, Minnesota
Childrens Hospital and Clinics of Minnesota- Minneapolis Not yet recruiting
Minneapolis, Minnesota, United States
Contact: Ellen Bendel-Stenzel, MD       Ellen.Bendel-Stenzel@childrensmn.org   
Childrens Hospital and Clinics of Minnesota- St Paul Not yet recruiting
St Paul, Minnesota, United States
Contact: Andrea Lampland, MD       alljmrh@aol.com   
United States, Missouri
Washington University Not yet recruiting
St. Louis, Missouri, United States, 63110
Contact: Amit Mathur, MD    314-454-4031    mathur_a@kids.wustl.edu   
Principal Investigator: Amit Mathur, MD         
Sub-Investigator: Robert McKinstry, MD         
United States, Ohio
Nationwide Children's Hospital Not yet recruiting
Columbus, Ohio, United States
Contact: Nathalie Maitre, MD       nathalie.maitre@Vanderbilt.Edu   
United States, Pennsylvania
University of Pittsburgh Not yet recruiting
Pittsburgh, Pennsylvania, United States
Contact: Toby Yanowitz, MD       yanotd@mail.magee.edu   
Sub-Investigator: Ashok Panigrahy, MD         
United States, Texas
UT Southwestern Not yet recruiting
Dallas, Texas, United States
Contact: Lina Chalak, MD       Lina.Chalak@UTSouthwestern.edu   
Children's Hospital San Antonio Not yet recruiting
San Antonio, Texas, United States
Contact: Kaashif Ahmad, MD       kaashif_ahmad@pediatrix.com   
United States, Utah
U of Utah Not yet recruiting
Salt Lake City, Utah, United States
Contact: Mariana Baserga, MD PhD       mariana.baserga@hsc.utah.edu   
United States, Washington
Seattle Children's Hospital Not yet recruiting
Seattle, Washington, United States, 98105
Contact: Dennis Mayock, MD    206-543-5257    mayock@u.washington.edu   
Sub-Investigator: Dennis Mayock, MD         
Principal Investigator: Sandra Juul, MD         
Sponsors and Collaborators
University of California, San Francisco
University of Washington
Mednax Center for Research, Education and Quality
University of Utah
Children's Research Institute
University of Minnesota - Clinical and Translational Science Institute
University of Texas
Washington University School of Medicine
Indiana University
Stanford University
University of Pittsburgh
University of California, Davis
Northwestern
Children's Hospital Los Angeles
Nationwide Children's Hospital
Johns Hopkins University
Boston University
University of New Mexico
University of Chicago
University of North Carolina
Investigators
Principal Investigator: Yvonne Wu, MD MPH University of California, San Francisco
  More Information

Publications:
Responsible Party: Yvonne Wu, Professor of Neurology and Pediatrics, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02811263     History of Changes
Other Study ID Numbers: P0511976 
Study First Received: June 17, 2016
Last Updated: June 20, 2016
Health Authority: United States: Food and Drug Administration
United States: Federal Government
United States: Data and Safety Monitoring Board
United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: No

Additional relevant MeSH terms:
Brain Diseases
Asphyxia Neonatorum
Asphyxia
Central Nervous System Diseases
Nervous System Diseases
Infant, Newborn, Diseases
Death
Pathologic Processes
Wounds and Injuries
Epoetin Alfa
Hematinics

ClinicalTrials.gov processed this record on December 06, 2016