<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01732146</url>
  </required_header>
  <id_info>
    <org_study_id>P110111</org_study_id>
    <secondary_id>2012-001417-17</secondary_id>
    <nct_id>NCT01732146</nct_id>
  </id_info>
  <brief_title>Efficacy of Erythropoietin to Improve Survival and Neurological Outcome in Hypoxic Ischemic Encephalopathy</brief_title>
  <acronym>Neurepo</acronym>
  <official_title>Phase III Study of Efficacy of High Dose Erythropoietin to Prevent Hypoxic-ischemic Encephalopathy Sequelae in Term Newborn</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the efficacy of high dose Erythropoietin to improve&#xD;
      survival and neurologic outcome in asphyxiated term newborn undergoing cooling.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hypoxic-ischemic encephalopathy remains the main cause of death or long term neurologic&#xD;
      impairments in neonates. Yet, therapies for birth asphyxia are currently limited. Hypothermia&#xD;
      when applied within 6 hours after birth demonstrate partial improvement in outcome of&#xD;
      newborns specially those with moderate form. Erythropoietin and its receptors are upregulated&#xD;
      after brain injury in ischemic conditions. Systemically administered erythropoietin is&#xD;
      neuroprotective in animal models of birth asphyxia. To date, one study demonstrate&#xD;
      improvement neurologic outcome in asphyxiated term newborn under erythropoietin treatment but&#xD;
      no reports evaluating beneficial of erythropoietin associated with cooling. This is a large&#xD;
      randomised controlled trial to evaluate the efficacy of high dose erythropoietin on outcome&#xD;
      at two years of asphyxiated term newborns undergoing cooling.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 28, 2013</start_date>
  <completion_date type="Actual">February 14, 2017</completion_date>
  <primary_completion_date type="Actual">February 14, 2017</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Survival without neurologic sequelae</measure>
    <time_frame>at 24 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mortality rates</measure>
    <time_frame>Within 24 months</time_frame>
    <description>number of dead patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of moderate and severe sequelae</measure>
    <time_frame>at 24 months</time_frame>
    <description>Mental Developmental index (Brunet Lezine Test), motor, visual and hearing impairment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aspect of brain lesions on MRI</measure>
    <time_frame>at day 6 and day 12 after birth</time_frame>
    <description>Brain MRI performed between day 6 and day 12 after birth</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tolerance of treatment</measure>
    <time_frame>at 24 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">120</enrollment>
  <condition>Hypoxic Ischemic Encephalopathy</condition>
  <arm_group>
    <arm_group_label>Erythropoietin beta</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1000 to 1500 U/kg/dose X 3 every 24 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>0.2 ml saline solution X 3 given every 24 hours</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>erythropoietin Beta</intervention_name>
    <description>erythropoietin intravenous injection (5000 U/ 0.3 ml)1000 to 1500 U/kg/dose X 3 given every 24 hours with the first dose within 12 hours of delivery</description>
    <arm_group_label>Erythropoietin beta</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>0.2 ml saline solution X 3 given every 24 hours with the first dose within 12 hours of delivery</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Term or near-term newborn (&gt; = 36 weeks gestational age)&#xD;
&#xD;
          -  Moderate to severe encephalopathy&#xD;
&#xD;
          -  undergoing moderate controlled hypothermia started within 6 hours after delivery :&#xD;
             rectal or esophageal temperature maintained at 33.5 ° C + / - 0.5 ° C before H6&#xD;
&#xD;
          -  Beneficiary of social security plan&#xD;
&#xD;
          -  Informed consent parental authority&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Impossibility of getting controlled hypothermia before H6&#xD;
&#xD;
          -  Infant older than 12 hours of age&#xD;
&#xD;
          -  Chromosomal or significant congenital abnormality&#xD;
&#xD;
          -  Predictable surgery in the first 3 days of life&#xD;
&#xD;
          -  Uncontrolled collapse&#xD;
&#xD;
          -  Haemorrhagic syndrome unchecked&#xD;
&#xD;
          -  Head trauma with or without skull fracture&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>12 Hours</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Juliana Patkai, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cochin Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cochin Hospital</name>
      <address>
        <city>Paris</city>
        <zip>75014</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Zhu C, Kang W, Xu F, Cheng X, Zhang Z, Jia L, Ji L, Guo X, Xiong H, Simbruner G, Blomgren K, Wang X. Erythropoietin improved neurologic outcomes in newborns with hypoxic-ischemic encephalopathy. Pediatrics. 2009 Aug;124(2):e218-26. doi: 10.1542/peds.2008-3553. Epub 2009 Jul 27.</citation>
    <PMID>19651565</PMID>
  </reference>
  <reference>
    <citation>Goodarzi MO, Carmina E, Azziz R. DHEA, DHEAS and PCOS. J Steroid Biochem Mol Biol. 2015 Jan;145:213-25. doi: 10.1016/j.jsbmb.2014.06.003. Epub 2014 Jul 5.</citation>
    <PMID>25008465</PMID>
  </reference>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>November 19, 2012</study_first_submitted>
  <study_first_submitted_qc>November 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 22, 2012</study_first_posted>
  <last_update_submitted>April 30, 2021</last_update_submitted>
  <last_update_submitted_qc>April 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hypoxic Ischemic Encephalopathy</keyword>
  <keyword>Term neonate</keyword>
  <keyword>Neuroprotection</keyword>
  <keyword>erythropoietin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Diseases</mesh_term>
    <mesh_term>Brain Ischemia</mesh_term>
    <mesh_term>Hypoxia-Ischemia, Brain</mesh_term>
    <mesh_term>Ischemia</mesh_term>
    <mesh_term>Hypoxia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epoetin Alfa</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01732146
org study id: P110111
secondary id: 2012-001417-17
nct id: NCT01732146
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine the efficacy of high dose Erythropoietin to improve
      survival and neurologic outcome in asphyxiated term newborn undergoing cooling.
Hypoxic-ischemic encephalopathy remains the main cause of death or long term neurologic
      impairments in neonates. Yet, therapies for birth asphyxia are currently limited. Hypothermia
      when applied within 6 hours after birth demonstrate partial improvement in outcome of
      newborns specially those with moderate form. Erythropoietin and its receptors are upregulated
      after brain injury in ischemic conditions. Systemically administered erythropoietin is
      neuroprotective in animal models of birth asphyxia. To date, one study demonstrate
      improvement neurologic outcome in asphyxiated term newborn under erythropoietin treatment but
      no reports evaluating beneficial of erythropoietin associated with cooling. This is a large
      randomised controlled trial to evaluate the efficacy of high dose erythropoietin on outcome
      at two years of asphyxiated term newborns undergoing cooling.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Survival without neurologic sequelae
time frame: at 24 months
measure: Mortality rates
time frame: Within 24 months
description: number of dead patients
measure: Rate of moderate and severe sequelae
time frame: at 24 months
description: Mental Developmental index (Brunet Lezine Test), motor, visual and hearing impairment
measure: Aspect of brain lesions on MRI
time frame: at day 6 and day 12 after birth
description: Brain MRI performed between day 6 and day 12 after birth
measure: Tolerance of treatment
time frame: at 24 months
arm group label: Erythropoietin beta
arm group type: Active Comparator
description: 1000 to 1500 U/kg/dose X 3 every 24 hours
arm group label: Placebo
arm group type: Placebo Comparator
description: 0.2 ml saline solution X 3 given every 24 hours
intervention type: Drug
intervention name: erythropoietin Beta
description: erythropoietin intravenous injection (5000 U/ 0.3 ml)1000 to 1500 U/kg/dose X 3 given every 24 hours with the first dose within 12 hours of delivery
arm group label: Erythropoietin beta
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
other name: 0.2 ml saline solution X 3 given every 24 hours with the first dose within 12 hours of delivery
criteria: 
gender: All
minimum age: N/A
maximum age: 12 Hours
healthy volunteers: No
last name: Juliana Patkai, MD, PhD
role: Principal Investigator
affiliation: Cochin Hospital
facility: 
country: France
citation: Zhu C, Kang W, Xu F, Cheng X, Zhang Z, Jia L, Ji L, Guo X, Xiong H, Simbruner G, Blomgren K, Wang X. Erythropoietin improved neurologic outcomes in newborns with hypoxic-ischemic encephalopathy. Pediatrics. 2009 Aug;124(2):e218-26. doi: 10.1542/peds.2008-3553. Epub 2009 Jul 27.
PMID: 19651565
citation: Goodarzi MO, Carmina E, Azziz R. DHEA, DHEAS and PCOS. J Steroid Biochem Mol Biol. 2015 Jan;145:213-25. doi: 10.1016/j.jsbmb.2014.06.003. Epub 2014 Jul 5.
PMID: 25008465
responsible party type: Sponsor
mesh term: Brain Diseases
mesh term: Brain Ischemia
mesh term: Hypoxia-Ischemia, Brain
mesh term: Ischemia
mesh term: Hypoxia
mesh term: Epoetin Alfa