<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/NCT03036072</url>
  </required_header>
  <id_info>
    <org_study_id>IRB 4489</org_study_id>
    <secondary_id>4KL2TR001063-04</secondary_id>
    <nct_id>NCT03036072</nct_id>
  </id_info>
  <brief_title>Delayed Rewarming for Neuroprotection in Infants Following Cardiopulmonary Bypass Surgery</brief_title>
  <official_title>Delayed Rewarming for Neuroprotection in Infants Following Cardiopulmonary Bypass Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alexa Craig</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>MaineHealth</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>MaineHealth</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an unblinded, single center, randomized study of infants with congenital heart&#xD;
      disease undergoing cardiopulmonary bypass surgery, randomized to either the delayed rewarming&#xD;
      intervention or to the standard of care (strict normothermia).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Control Group:&#xD;
&#xD;
      The congenital heart surgery will be performed according to usual practice with the degree of&#xD;
      intra-operative hypothermia determined by the cardiothoracic surgeon based on the anticipated&#xD;
      complexity of the case. Following completion of the surgical procedure, the infant will be&#xD;
      rapidly rewarmed on CPB at a rate of 0.2 to 0.3°C per minute to a normothermic temperature of&#xD;
      36.5°C. Infants in this group will be given a single weight-based 15 mg/kg dose of&#xD;
      intravenous Tylenol in the operating room (OR) by the anesthesiologist as the chest is being&#xD;
      closed. The infant will be transported to the Pediatric Intensive Care Unit (PICU) for&#xD;
      routine post-operative monitoring. If the infant develops a fever, ice packs will be applied&#xD;
      to the axilla and groin per usual routine and removed once the fever has abated.&#xD;
&#xD;
      Experimental group:&#xD;
&#xD;
      Partial rewarming will occur on CPB to 35°C. During the last hour of surgery, the infant's&#xD;
      temperature will be maintained at 35°C while the chest is closed by using a BairHugger and&#xD;
      lowering the room temperature. Transfusions of packed red blood cells, fresh frozen plasma&#xD;
      and cryoprecipitate will not be automatically warmed. Infants will be given a single 15 mg/kg&#xD;
      dose of IV Tylenol in the OR. The infant will be transported to the PICU at 35°C and placed&#xD;
      on the temperature-regulating blanket. The infant will be incrementally rewarmed with&#xD;
      increases in temperature of 0.3°C every 2 hours for 6 hours, then 0.2°C every 2 hours for 6&#xD;
      hours to the goal temperature of 36.5°C. Once the infant is stable, EEG will be performed for&#xD;
      48 hours to screen for seizures. The PI will interpret the EEG every 6-8 hours. The infant&#xD;
      will remain on the blanket at 36.5°C for another 12 hours. The blanket and esophageal&#xD;
      temperature probe will then be removed a total of 24 hours after surgery was completed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2016</start_date>
  <completion_date type="Actual">May 2019</completion_date>
  <primary_completion_date type="Actual">April 2018</primary_completion_date>
  <phase>N/A</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Infants With Elevated s100b and NSE</measure>
    <time_frame>4 days</time_frame>
    <description>In a population of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, does delayed rewarming administered during the 12 hours after surgery, compared to standard care, decrease brain injury as measured by levels of serum biomarkers of brain injury, s100b and neuron specific enolase during the four days after surgery?</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>4 days</time_frame>
    <description>In a population of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, is there evidence for increased frequency of severe, moderate or other adverse events in the delayed rewarming group compared to the standard of care group?</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Post-Op Complication</condition>
  <arm_group>
    <arm_group_label>Strict Normothermia</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will be rewarmed to 36.5 degrees centigrade in the operating room and maintained here by conventional means in the PICU.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Delayed Rewarming</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient will be rewarmed to 35.0 degrees centigrade in the operating room, then slowly rewarmed to normal physiologic temperature over 12 hours by using a servo-controlled cooling blanket. Normothermia will be maintained by the cooling blanket for an additional 12 hours.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Strict normothermia</intervention_name>
    <arm_group_label>Strict Normothermia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Delayed Rewarming</intervention_name>
    <description>Use of the servo-controlled cooling blanket for delayed rewarming to target temperature.</description>
    <arm_group_label>Delayed Rewarming</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of congenital heart disease requiring congenital heart surgery on bypass&#xD;
&#xD;
          2. Age less than 6 months at the time of surgery&#xD;
&#xD;
          3. Intra-operative hypothermia less than or equal to 35°C&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Concern for underlying coagulation disorder such as hemophilia&#xD;
&#xD;
          2. Death in the operating room&#xD;
&#xD;
          3. Inability to wean of cardiopulmonary bypass at conclusion of surgery&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>6 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexa K Craig, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assistant Professor of Pediatrics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maine Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Maine</state>
        <zip>04102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2020</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 30, 2017</study_first_posted>
  <results_first_submitted>April 3, 2020</results_first_submitted>
  <results_first_submitted_qc>April 3, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">April 15, 2020</results_first_posted>
  <last_update_submitted>June 30, 2020</last_update_submitted>
  <last_update_submitted_qc>June 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>MaineHealth</investigator_affiliation>
    <investigator_full_name>Alexa Craig</investigator_full_name>
    <investigator_title>Assistant Professor of Pediatrics</investigator_title>
  </responsible_party>
  <keyword>Therapeutic Hypothermia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Postoperative Complications</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 31, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/72/NCT03036072/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Strict Normothermia</title>
          <description>Patients will be rewarmed to 36.5 degrees centigrade in the operating room and maintained here by conventional means in the PICU.&#xD;
Strict normothermia</description>
        </group>
        <group group_id="P2">
          <title>Delayed Rewarming</title>
          <description>Patient will be rewarmed to 35.0 degrees centigrade in the operating room, then slowly rewarmed to normal physiologic temperature (36.5) over 12 hours by using a servo-controlled cooling blanket. Normothermia will be maintained by the cooling blanket for an additional 12 hours.&#xD;
Delayed Rewarming: Use of the servo-controlled cooling blanket for delayed rewarming to target temperature.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Strict Normothermia</title>
          <description>Patients will be rewarmed to 36.5 degrees centigrade in the operating room and maintained here by conventional means in the PICU.&#xD;
Strict normothermia</description>
        </group>
        <group group_id="B2">
          <title>Delayed Rewarming</title>
          <description>Patient will be rewarmed to 35.0 degrees centigrade in the operating room, then slowly rewarmed to normal physiologic temperature (36.5) over 12 hours by using a servo-controlled cooling blanket. Normothermia will be maintained by the cooling blanket for an additional 12 hours.&#xD;
Delayed Rewarming: Use of the servo-controlled cooling blanket for delayed rewarming to target temperature.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="22"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Less than 2 weeks at surgery</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>More than 2 weeks at surgery</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Trisomy 21</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Infants With Elevated s100b and NSE</title>
        <description>In a population of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, does delayed rewarming administered during the 12 hours after surgery, compared to standard care, decrease brain injury as measured by levels of serum biomarkers of brain injury, s100b and neuron specific enolase during the four days after surgery?</description>
        <time_frame>4 days</time_frame>
        <population>Laboratory storage and transportation issues resulted in less than expected number of viable specimens that could be analyzed at all 5 time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Strict Normothermia</title>
            <description>Patients will be rewarmed to 36.5 degrees centigrade in the operating room and maintained here by conventional means in the PICU.&#xD;
Strict normothermia</description>
          </group>
          <group group_id="O2">
            <title>Delayed Rewarming</title>
            <description>Patient will be rewarmed to 35.0 degrees centigrade in the operating room, then slowly rewarmed to normal physiologic temperature (36.5) over 12 hours by using a servo-controlled cooling blanket. Normothermia will be maintained by the cooling blanket for an additional 12 hours.&#xD;
Delayed Rewarming: Use of the servo-controlled cooling blanket for delayed rewarming to target temperature.</description>
          </group>
        </group_list>
        <measure>
          <title>Infants With Elevated s100b and NSE</title>
          <description>In a population of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, does delayed rewarming administered during the 12 hours after surgery, compared to standard care, decrease brain injury as measured by levels of serum biomarkers of brain injury, s100b and neuron specific enolase during the four days after surgery?</description>
          <population>Laboratory storage and transportation issues resulted in less than expected number of viable specimens that could be analyzed at all 5 time points.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events</title>
        <description>In a population of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, is there evidence for increased frequency of severe, moderate or other adverse events in the delayed rewarming group compared to the standard of care group?</description>
        <time_frame>4 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Strict Normothermia</title>
            <description>Patients will be rewarmed to 36.5 degrees centigrade in the operating room and maintained here by conventional means in the PICU.&#xD;
Strict normothermia</description>
          </group>
          <group group_id="O2">
            <title>Delayed Rewarming</title>
            <description>Patient will be rewarmed to 35.0 degrees centigrade in the operating room, then slowly rewarmed to normal physiologic temperature (36.5) over 12 hours by using a servo-controlled cooling blanket. Normothermia will be maintained by the cooling blanket for an additional 12 hours.&#xD;
Delayed Rewarming: Use of the servo-controlled cooling blanket for delayed rewarming to target temperature.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <description>In a population of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, is there evidence for increased frequency of severe, moderate or other adverse events in the delayed rewarming group compared to the standard of care group?</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Until 48 hours post surgery.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Strict Normothermia</title>
          <description>Patients will be rewarmed to 36.5 degrees centigrade in the operating room and maintained here by conventional means in the PICU.&#xD;
Strict normothermia</description>
        </group>
        <group group_id="E2">
          <title>Delayed Rewarming</title>
          <description>Patient will be rewarmed to 35.0 degrees centigrade in the operating room, then slowly rewarmed to normal physiologic temperature (36.5) over 12 hours by using a servo-controlled cooling blanket. Normothermia will be maintained by the cooling blanket for an additional 12 hours.&#xD;
Delayed Rewarming: Use of the servo-controlled cooling blanket for delayed rewarming to target temperature.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>ECMO after surgery</sub_title>
                <description>Patient unable to wean from bypass following surgery.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>CPR after surgery</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Return to Operating Room</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="12"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Stroke or Seizure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Alexa Craig, MD</name_or_title>
      <organization>Maine Medical Center</organization>
      <phone>207-396-6920</phone>
      <email>craiga@mmc.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03036072
org study id: IRB 4489
secondary id: 4KL2TR001063-04
nct id: NCT03036072
lead sponsor: 
collaborator: 
has dmc: Yes
This is an unblinded, single center, randomized study of infants with congenital heart
      disease undergoing cardiopulmonary bypass surgery, randomized to either the delayed rewarming
      intervention or to the standard of care (strict normothermia).
Control Group:

      The congenital heart surgery will be performed according to usual practice with the degree of
      intra-operative hypothermia determined by the cardiothoracic surgeon based on the anticipated
      complexity of the case. Following completion of the surgical procedure, the infant will be
      rapidly rewarmed on CPB at a rate of 0.2 to 0.3°C per minute to a normothermic temperature of
      36.5°C. Infants in this group will be given a single weight-based 15 mg/kg dose of
      intravenous Tylenol in the operating room (OR) by the anesthesiologist as the chest is being
      closed. The infant will be transported to the Pediatric Intensive Care Unit (PICU) for
      routine post-operative monitoring. If the infant develops a fever, ice packs will be applied
      to the axilla and groin per usual routine and removed once the fever has abated.

      Experimental group:

      Partial rewarming will occur on CPB to 35°C. During the last hour of surgery, the infant's
      temperature will be maintained at 35°C while the chest is closed by using a BairHugger and
      lowering the room temperature. Transfusions of packed red blood cells, fresh frozen plasma
      and cryoprecipitate will not be automatically warmed. Infants will be given a single 15 mg/kg
      dose of IV Tylenol in the OR. The infant will be transported to the PICU at 35°C and placed
      on the temperature-regulating blanket. The infant will be incrementally rewarmed with
      increases in temperature of 0.3°C every 2 hours for 6 hours, then 0.2°C every 2 hours for 6
      hours to the goal temperature of 36.5°C. Once the infant is stable, EEG will be performed for
      48 hours to screen for seizures. The PI will interpret the EEG every 6-8 hours. The infant
      will remain on the blanket at 36.5°C for another 12 hours. The blanket and esophageal
      temperature probe will then be removed a total of 24 hours after surgery was completed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Infants With Elevated s100b and NSE
time frame: 4 days
description: In a population of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, does delayed rewarming administered during the 12 hours after surgery, compared to standard care, decrease brain injury as measured by levels of serum biomarkers of brain injury, s100b and neuron specific enolase during the four days after surgery?
measure: Number of Participants With Adverse Events
time frame: 4 days
description: In a population of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, is there evidence for increased frequency of severe, moderate or other adverse events in the delayed rewarming group compared to the standard of care group?
arm group label: Strict Normothermia
arm group type: Active Comparator
description: Patients will be rewarmed to 36.5 degrees centigrade in the operating room and maintained here by conventional means in the PICU.
arm group label: Delayed Rewarming
arm group type: Experimental
description: Patient will be rewarmed to 35.0 degrees centigrade in the operating room, then slowly rewarmed to normal physiologic temperature over 12 hours by using a servo-controlled cooling blanket. Normothermia will be maintained by the cooling blanket for an additional 12 hours.
intervention type: Other
intervention name: Strict normothermia
arm group label: Strict Normothermia
intervention type: Device
intervention name: Delayed Rewarming
description: Use of the servo-controlled cooling blanket for delayed rewarming to target temperature.
arm group label: Delayed Rewarming
criteria: 
gender: All
minimum age: N/A
maximum age: 6 Months
healthy volunteers: No
last name: Alexa K Craig, MD, MSc
role: Principal Investigator
affiliation: Assistant Professor of Pediatrics
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: MaineHealth
investigator full name: Alexa Craig
investigator title: Assistant Professor of Pediatrics
mesh term: Postoperative Complications
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 