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Trial record 3 of 57 for:    neurology AND University AND San Francisco | Open Studies

High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2017 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
Children's Hospital Los Angeles
Nationwide Children's Hospital
Boston University
University of New Mexico
University of Chicago
University of North Carolina
University of Arkansas
Vanderbilt University
Children's Hospital Medical Center, Cincinnati
Information provided by (Responsible Party):
Yvonne Wu, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT02811263
First received: June 17, 2016
Last updated: May 22, 2017
Last verified: May 2017
  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
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, 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 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


Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • Rates of Epo-related adverse events [ Time Frame: Through hospital discharge ]
  • Rates of Epo-related adverse events [ Time Frame: Through 22-26 months ]
  • Serial circulating biomarkers of inflammation/brain injury [ Time Frame: During first week of life ]
  • MR evidence of brain injury [ Time Frame: During first week of life ]

Estimated Enrollment: 500
Study Start Date: January 2017
Estimated Study Completion Date: September 2022
Estimated Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Erythropoietin
Erythropoietin 1000 U/kg IV, at about 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 about 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. 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.
  Eligibility

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

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., endotracheal or mask ventilation, or chest compressions), or
    3. pH < 7.00 in cord, arterial, or venous blood < 60 minutes of age
    4. 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

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 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)
  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: Sandra Juul, MD PHD sjuul@uw.edu

Locations
United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States
Contact: Tai-Wei Wu, MD       twu@chla.usc.edu   
Principal Investigator: Tai-Wei Wu, MD         
Stanford University Recruiting
Palo Alto, California, United States
Contact: Krisa Van Meurs, MD         
Contact: Elizabeth Ball, RN    (650) 725-8342    mbball@stanford.edu   
Principal Investigator: Krisa Van Meurs, MD         
University of California, San Francisco Recruiting
San Francisco, California, United States, 94158
Contact: Fernando Gonzalez, MD       Fernando.Gonzalez@ucsf.edu   
Principal Investigator: Fernando Gonzalez, MD         
Sub-Investigator: Yvonne Wu, MD MPH         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, D.C., 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, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States
Contact: Ulrike Mietzsch, MD       umietzsc@iu.edu   
Principal Investigator: Ulrike Mietzsch, MD         
Sub-Investigator: Mandy Harris, MD         
United States, Minnesota
Children's Hospitals and Clinics of Minnesota: Minneapolis Not yet recruiting
Minneapolis, Minnesota, United States
Contact: Ellen Bendel-Stenzel, MD       Ellen.Bendel-Stenzel@childrensmn.org   
Principal Investigator: Ellen Bendel-Stenzel, MD         
Children's Hospitals and Clinics of Minnesota: St. Paul Recruiting
Saint Paul, Minnesota, United States
Contact: Andrea Lampland, MD       lampl002@umn.edu   
Principal Investigator: Andrea Lampland, MD         
United States, Missouri
Washington University Recruiting
Saint 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
Cincinnati Children's Hospital Medical Center Not yet recruiting
Cincinnati, Ohio, United States
Contact: Brenda Poindexter, MD MS       Brenda.Poindexter@cchmc.org   
Principal Investigator: Brenda Poindexter, MD MS         
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States
Contact: Nathalie Maitre, MD       nathalie.Maitre@nationwidechildrens.org   
Principal Investigator: Nathalie Maitre, MD         
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC Not yet recruiting
Pittsburgh, Pennsylvania, United States
Contact: Toby Yaoniwtz, MD       yanotd@mail.magee.edu   
Principal Investigator: Toby Yanowitz, MD         
Sub-Investigator: Ashok Panigrahy, MD         
Magee Women's Hospital of UPMC Recruiting
Pittsburgh, Pennsylvania, United States
Contact: Toby Yanowitz, MD       yanotd@mail.magee.edu   
Principal Investigator: Toby Yanowitz, MD         
Sub-Investigator: Ashok Panigrahy, MD         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States
Contact: Hendrik Weitkamp, MD       hendrik.weitkamp@Vanderbilt.Edu   
Principal Investigator: Hendrik Weitkamp, MD         
United States, Texas
UT Southwestern Not yet recruiting
Dallas, Texas, United States
Contact: Lina Chalak, MD       Lina.Chalak@UTSouthwestern.edu   
Principal Investigator: Lina Chalak, MD         
Children's Hospital of San Antonio Recruiting
San Antonio, Texas, United States
Contact: Kaashif Ahmad, MD       kaashif_ahmad@pediatrix.com   
Principal Investigator: Kaashif Ahmad, MD         
Methodist Children's Hospital Recruiting
San Antonio, Texas, United States
Contact: Kaashif Ahmad, MD       kaashif_ahmad@pediatrix.com   
Principal Investigator: Kaashif Ahmad, MD         
United States, Utah
Intermountain Medical Center Recruiting
Salt Lake City, Utah, United States
Contact: Mariana Baserga, MD MSCI       mariana.baserga@hsc.utah.edu   
Principal Investigator: Mariana Baserga, MD MSCI         
Primary Children's Hospital Recruiting
Salt Lake City, Utah, United States
Contact: Mariana Baserga, MD MSCI       mariana.baserga@hsc.utah.edu   
Principal Investigator: Mariana Baserga, MD MSCI         
University of Utah Recruiting
Salt Lake City, Utah, United States
Contact: Mariana Baserga, MD MSCI       mariana.baserga@hsc.utah.edu   
Principal Investigator: Mariana Baserga, MD MSCI         
United States, Washington
Seattle Children's Hospital Recruiting
Seattle, Washington, United States, 98105
Contact: Dennis Mayock, MD    206-543-5257    mayock@u.washington.edu   
Principal Investigator: Dennis Mayock, MD         
Sub-Investigator: Sandra Juul, MD PhD         
University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98195
Contact: Dennis Mayock, MD    206-543-5257    mayock@u.washington.edu   
Principal Investigator: Dennis Mayock, MD         
Sub-Investigator: Sandra Juul, MD PhD         
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
Children's Hospital Los Angeles
Nationwide Children's Hospital
Boston University
University of New Mexico
University of Chicago
University of North Carolina
University of Arkansas
Vanderbilt University
Children's Hospital Medical Center, Cincinnati
Investigators
Principal Investigator: Yvonne Wu, MD MPH University of California, San Francisco
Principal Investigator: Sandra Juul, MD PHD University of Washington
  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: May 22, 2017
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 May 25, 2017