<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/NCT01675388</url>
  </required_header>
  <id_info>
    <org_study_id>1006008466</org_study_id>
    <nct_id>NCT01675388</nct_id>
  </id_info>
  <brief_title>Hypothermia During ECMO to Decrease Brain Injury</brief_title>
  <official_title>Hypothermia as Neuroprotection During ECMO: Is Brain MRI a Biomarker of Outcomes?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sood, Beena G., MD, MS</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sood, Beena G., MD, MS</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Newborn infants with severe respiratory failure are treated with extracorporeal membrane&#xD;
      oxygenation (ECMO), a modified form of cardiopulmonary bypass. These infants as at risk for&#xD;
      brain injury as a result of hypoxia and blood flow changes in the brain prior to and during&#xD;
      ECMO. The investigators propose a clinical trial of a novel treatment (cooling during ECMO)&#xD;
      and novel diagnostic tool (advanced MRI techniques) that will lead to improved outcomes,&#xD;
      early diagnosis and intervention for brain injury, decreased cost and duration of clinical&#xD;
      trials, decrease in the burden of chronic neurologic disease and disability in society, thus&#xD;
      improving the health and quality of life of these infants as they progress through childhood&#xD;
      into adulthood.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Term and late preterm neonates with severe hypoxemic respiratory failure [NHRF] receive&#xD;
      extracorporeal membrane oxygenation (ECMO), a modified form of cardiopulmonary bypass, when&#xD;
      maximal conventional therapy fails. Although ECMO significantly improves survival and&#xD;
      decreases disability, 15-50% of survivors nevertheless have poor neurodevelopmental [ND]&#xD;
      outcomes due to hypoxemia and cerebral hypoperfusion occurring prior to and during ECMO.&#xD;
      Hypothermia [HYP] (33 deg-34 deg C for 48-72 hours) has been shown to improve ND outcomes and&#xD;
      following neonatal hypoxic-ischemic encephalopathy [NE]. Whether the addition of hypothermia&#xD;
      to ECMO for severe NHRF will improve ND outcomes is unknown. Long-term evaluation of ND&#xD;
      outcomes is the gold standard for determining the full spectrum of developmental disabilities&#xD;
      as neonatal clinical findings; biochemical and electrophysiological tests; and cranial&#xD;
      sonography have limited predictive value. Conventional magnetic resonance imaging [MRI] has a&#xD;
      predictive accuracy of &gt; 0.8 for death and disability following NE. MR abnormalities in&#xD;
      infants undergoing ECMO for NHRF differ from those seen in NE and there are no systematic&#xD;
      reports on the ND implications of MR abnormalities seen in NHRF treated with ECMO. Given the&#xD;
      societal and economic costs associated with poor long-term ND outcomes and the challenges of&#xD;
      neurologic assessment in critically ill neonates receiving ECMO for NHRF, there is an urgent&#xD;
      need for (i) neuroprotection pre-/during ECMO to decrease brain injury and (ii) innovative&#xD;
      diagnostic modalities to enable early diagnosis and intervention.&#xD;
&#xD;
      Our goal is to improve the treatment and ND outcomes in neonates with NHRF. The overall&#xD;
      objectives of this proposal are to establish the neuroprotective role of hypothermia during&#xD;
      ECMO for NHRF as evaluated by ND assessment at 18-22 months [mo] of age and to validate the&#xD;
      use of conventional and advanced MR techniques as biomarkers of brain injury. The central&#xD;
      hypotheses are that (i) HYP to 33.5°C during the 1st 72 hours of ECMO in NHRF will reduce the&#xD;
      extent and severity of brain injury as evaluated by Bayley Scales of Infant Development&#xD;
      (BSID-III) cognitive scores at 18-22 mo and proportion of normal MRI studies in the neonatal&#xD;
      period and at 18-22 mo; and (ii) conventional and advanced MR techniques in the neonatal&#xD;
      period and at 18-22 mo will be biomarkers of brain injury allowing prediction of ND outcomes,&#xD;
      and monitoring of post-injury brain growth and plasticity.&#xD;
&#xD;
      The specific aims are to evaluate:&#xD;
&#xD;
        1. Safety and efficacy of hypothermia combined with ECMO for NHRF in improving&#xD;
           neurodevelopmental outcomes at 18-22 months of age&#xD;
&#xD;
        2. MR abnormalities in the neonatal period and at 18-22 months of age and their predictive&#xD;
           accuracy for neurodevelopmental outcomes at 18-22 months of age following hypothermia&#xD;
           during ECMO for NHRF&#xD;
&#xD;
      MRI will be obtained in the neonatal period as part of routine clinical care; MRI will be&#xD;
      repeated at 18-22 mo of age on an outpatient basis if funding is available to assess&#xD;
      longitudinal changes in brain structure and metabolite profile following ECMO for NHRF and to&#xD;
      correlate these with ND outcomes at 18-22 mo of age.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No funding&#xD;
  </why_stopped>
  <start_date>August 2012</start_date>
  <completion_date type="Anticipated">August 2017</completion_date>
  <primary_completion_date type="Anticipated">August 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>BSID-III cognitive scores at 18-22 mo</measure>
    <time_frame>18-22 months of age</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical findings in the neonatal period and at 18-22 mos</measure>
    <time_frame>18-22 months</time_frame>
    <description>i) outcomes in the neonatal intensive care unit (NICU): HUS findings, type of ECMO, death/withdrawal of intensive care, acute AEs, cardio-respiratory support, infections, need for gavage/gastrostomy-tube feeds, length of hospital stay, bronchopulmonary dysplasia, neurologic status, and growth parameter at discharge ii) outcomes after discharge: post-neonatal deaths, number of re-hospitalizations, seizure disorder, growth parameters, BSID-III subscales at 18-22 mo, visual impairment, hearing impairment, multiple disabilities</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRI findings in the neonatal period and at 18-22 mos</measure>
    <time_frame>18-22 months</time_frame>
    <description>MRIs at 18-22 months will only be evaluated if funding for obatining MRIs becomes available</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Neonatal Respiratory Failure</condition>
  <arm_group>
    <arm_group_label>Hypothermia</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Hypothermia to 33.5 deg Centigrade</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Hypothermia</intervention_name>
    <description>Hypothermia to 33.5 deg C</description>
    <arm_group_label>Hypothermia</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Neonates ≥ 34 weeks gestational age and postnatal age ≤ 28 days&#xD;
&#xD;
          -  Presence of severe reversible NHRF qualifying for ECMO based on institutional&#xD;
             guidelines including:&#xD;
&#xD;
               -  Oxygenation Index &gt; 35 ([mean airway pressure in cmH2O x Fractional inspired O2&#xD;
                  concentration x 100]/Arterial O2 tension in mmHg) or&#xD;
&#xD;
               -  Alveolar-arterial oxygen gradient &gt; 600 mmHg for 4 h&#xD;
&#xD;
          -  Infants undergoing veno-arterial or veno-venous ECMO&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lethal chromosomal and congenital anomalies including congenital diaphragmatic hernia&#xD;
             (CDH) Infants with CDH, who constitute a third of neonates undergoing ECMO, have been&#xD;
             excluded because the high mortality and morbidity is related more to the underlying&#xD;
             lung abnormality and practice variation in timing of CDH repair rather than to NHRF.&#xD;
&#xD;
          -  ECMO for post operative cardiac support&#xD;
&#xD;
          -  Neonates with a birth weight &lt; 1.8 kg&#xD;
&#xD;
          -  Initiation of HYP for NE prior to initiating ECMO for NHRF&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>28 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Beena G. Sood</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wayne State University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital of Michigan</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2014</verification_date>
  <study_first_submitted>August 24, 2012</study_first_submitted>
  <study_first_submitted_qc>August 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 30, 2012</study_first_posted>
  <last_update_submitted>November 17, 2014</last_update_submitted>
  <last_update_submitted_qc>November 17, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 18, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sood, Beena G., MD, MS</investigator_affiliation>
    <investigator_full_name>Beena G. Sood, MD, MS</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Neonatal hypoxemic respiratory failure</keyword>
  <keyword>Extra Corporeal Membrane Oxygenation</keyword>
  <keyword>Neurodevelopmental outcomes</keyword>
  <keyword>Neuroimaging</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Insufficiency</mesh_term>
    <mesh_term>Hypothermia</mesh_term>
  </condition_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/NCT01675388
org study id: 1006008466
nct id: NCT01675388
lead sponsor: 
has dmc: No
Newborn infants with severe respiratory failure are treated with extracorporeal membrane
      oxygenation (ECMO), a modified form of cardiopulmonary bypass. These infants as at risk for
      brain injury as a result of hypoxia and blood flow changes in the brain prior to and during
      ECMO. The investigators propose a clinical trial of a novel treatment (cooling during ECMO)
      and novel diagnostic tool (advanced MRI techniques) that will lead to improved outcomes,
      early diagnosis and intervention for brain injury, decreased cost and duration of clinical
      trials, decrease in the burden of chronic neurologic disease and disability in society, thus
      improving the health and quality of life of these infants as they progress through childhood
      into adulthood.
Term and late preterm neonates with severe hypoxemic respiratory failure [NHRF] receive
      extracorporeal membrane oxygenation (ECMO), a modified form of cardiopulmonary bypass, when
      maximal conventional therapy fails. Although ECMO significantly improves survival and
      decreases disability, 15-50% of survivors nevertheless have poor neurodevelopmental [ND]
      outcomes due to hypoxemia and cerebral hypoperfusion occurring prior to and during ECMO.
      Hypothermia [HYP] (33 deg-34 deg C for 48-72 hours) has been shown to improve ND outcomes and
      following neonatal hypoxic-ischemic encephalopathy [NE]. Whether the addition of hypothermia
      to ECMO for severe NHRF will improve ND outcomes is unknown. Long-term evaluation of ND
      outcomes is the gold standard for determining the full spectrum of developmental disabilities
      as neonatal clinical findings; biochemical and electrophysiological tests; and cranial
      sonography have limited predictive value. Conventional magnetic resonance imaging [MRI] has a
      predictive accuracy of > 0.8 for death and disability following NE. MR abnormalities in
      infants undergoing ECMO for NHRF differ from those seen in NE and there are no systematic
      reports on the ND implications of MR abnormalities seen in NHRF treated with ECMO. Given the
      societal and economic costs associated with poor long-term ND outcomes and the challenges of
      neurologic assessment in critically ill neonates receiving ECMO for NHRF, there is an urgent
      need for (i) neuroprotection pre-/during ECMO to decrease brain injury and (ii) innovative
      diagnostic modalities to enable early diagnosis and intervention.

      Our goal is to improve the treatment and ND outcomes in neonates with NHRF. The overall
      objectives of this proposal are to establish the neuroprotective role of hypothermia during
      ECMO for NHRF as evaluated by ND assessment at 18-22 months [mo] of age and to validate the
      use of conventional and advanced MR techniques as biomarkers of brain injury. The central
      hypotheses are that (i) HYP to 33.5°C during the 1st 72 hours of ECMO in NHRF will reduce the
      extent and severity of brain injury as evaluated by Bayley Scales of Infant Development
      (BSID-III) cognitive scores at 18-22 mo and proportion of normal MRI studies in the neonatal
      period and at 18-22 mo; and (ii) conventional and advanced MR techniques in the neonatal
      period and at 18-22 mo will be biomarkers of brain injury allowing prediction of ND outcomes,
      and monitoring of post-injury brain growth and plasticity.

      The specific aims are to evaluate:

        1. Safety and efficacy of hypothermia combined with ECMO for NHRF in improving
           neurodevelopmental outcomes at 18-22 months of age

        2. MR abnormalities in the neonatal period and at 18-22 months of age and their predictive
           accuracy for neurodevelopmental outcomes at 18-22 months of age following hypothermia
           during ECMO for NHRF

      MRI will be obtained in the neonatal period as part of routine clinical care; MRI will be
      repeated at 18-22 mo of age on an outpatient basis if funding is available to assess
      longitudinal changes in brain structure and metabolite profile following ECMO for NHRF and to
      correlate these with ND outcomes at 18-22 mo of age.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: BSID-III cognitive scores at 18-22 mo
time frame: 18-22 months of age
measure: Clinical findings in the neonatal period and at 18-22 mos
time frame: 18-22 months
description: i) outcomes in the neonatal intensive care unit (NICU): HUS findings, type of ECMO, death/withdrawal of intensive care, acute AEs, cardio-respiratory support, infections, need for gavage/gastrostomy-tube feeds, length of hospital stay, bronchopulmonary dysplasia, neurologic status, and growth parameter at discharge ii) outcomes after discharge: post-neonatal deaths, number of re-hospitalizations, seizure disorder, growth parameters, BSID-III subscales at 18-22 mo, visual impairment, hearing impairment, multiple disabilities
measure: MRI findings in the neonatal period and at 18-22 mos
time frame: 18-22 months
description: MRIs at 18-22 months will only be evaluated if funding for obatining MRIs becomes available
arm group label: Hypothermia
arm group type: Experimental
description: Hypothermia to 33.5 deg Centigrade
intervention type: Other
intervention name: Hypothermia
description: Hypothermia to 33.5 deg C
arm group label: Hypothermia
criteria: 
gender: All
minimum age: 1 Day
maximum age: 28 Days
healthy volunteers: No
last name: Beena G. Sood
role: Principal Investigator
affiliation: Wayne State University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Sood, Beena G., MD, MS
investigator full name: Beena G. Sood, MD, MS
investigator title: Associate Professor
mesh term: Respiratory Insufficiency
mesh term: Hypothermia