<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/NCT04494867</url>
  </required_header>
  <id_info>
    <org_study_id>COVID-19 Core Warming</org_study_id>
    <nct_id>NCT04494867</nct_id>
  </id_info>
  <brief_title>Core Warming in COVID-19 Patients Undergoing Mechanical Ventilation</brief_title>
  <official_title>Core Warming of COVID-19 Patients Undergoing Mechanical Ventilation: a Randomized, Single Center Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sharp HealthCare</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Advanced Cooling Therapy, Inc., d/b/a Attune Medical</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Sharp HealthCare</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the proposed pilot study is to determine if core warming improves respiratory&#xD;
      physiology of mechanically ventilated patients with COVID-19, allowing earlier weaning from&#xD;
      ventilation, and greater overall survival.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a small scale pilot study to evaluate if core warming improves respiratory physiology&#xD;
      of mechanically ventilated patients with COVID-19, allowing earlier weaning from ventilation,&#xD;
      and greater overall survival. This prospective, randomized study will include 20 patients&#xD;
      diagnosed with COVID-19, and undergoing mechanical ventilation for the treatment of&#xD;
      respiratory failure. Patients will be randomized in a 1:1 fashion with 10 patients (Group A)&#xD;
      randomized to undergo core warming, and the other 10 patients (Group B) serving as the&#xD;
      control group who will not have the ensoETM device used. Patients randomized to Group A will&#xD;
      have core warming initiated in the ICU or other clinical environment in which they are being&#xD;
      treated after enrollment and provision of informed consent from appropriate surrogate or&#xD;
      legally authorized representative.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 19, 2020</start_date>
  <completion_date type="Actual">February 28, 2022</completion_date>
  <primary_completion_date type="Actual">February 28, 2022</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PaO2/FiO2 Ratio</measure>
    <time_frame>0, 24, 48, and 72 hours after initiation of core warming</time_frame>
    <description>Determine the change in PaO2/FiO2 ratio at 0, 24, 48, and 72 hours after implementation of core warming of ventilated patients, and compare this change to patients undergoing standard care.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cycle Threshold at 72-hours</measure>
    <time_frame>72 hours after initiation of core warming</time_frame>
    <description>Determine the change cycle threshold after implementation of core warming of ventilated patients, and compare this change to patients undergoing standard care.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilator-Free Days</measure>
    <time_frame>Initiation of Core Warming Until Patient Weaned Off Mechanical Ventilation</time_frame>
    <description>Measure the impact of core warming on duration of mechanical ventilation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>30-Day Mortality</measure>
    <time_frame>30 days after initiation of core warming</time_frame>
    <description>Determine impact of core warming on patient mortality.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>Core warming</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive the Attune Medical Esophageal Heat Transfer Device (EnsoETM) and undergo core warming</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive standard temperature management and treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Core Warming</intervention_name>
    <description>Esophageal heat transfer device will be set to 42°C temperature after initial placement, and maintained at 42°C for the duration of treatment.</description>
    <arm_group_label>Core warming</arm_group_label>
    <other_name>EnsoETM</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard of Care</intervention_name>
    <description>Standard temperature management and treatment</description>
    <arm_group_label>Standard of Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients above the age of 18 years old.&#xD;
&#xD;
          -  Patients with a diagnosis of COVID-19 on mechanical ventilation.&#xD;
&#xD;
          -  Patient maximum baseline temperature (within previous 12 hours) &lt; 38.3°C.&#xD;
&#xD;
          -  Patients must have a surrogate or legally authorized representative able to understand&#xD;
             and critically review the informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients without surrogate or legally authorized representative able to provide&#xD;
             informed consent.&#xD;
&#xD;
          -  Patients with contraindication to core warming using an esophageal core warming&#xD;
             device.&#xD;
&#xD;
          -  Patients known to be pregnant.&#xD;
&#xD;
          -  Patients with &lt;40 kg of body mass.&#xD;
&#xD;
          -  Patients with DNR status.&#xD;
&#xD;
          -  Patients with acute stroke, post-cardiac arrest, or multiple sclerosis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David Willms, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sharp HealthCare</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ahmed Salem, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sharp HealthCare</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sharp Memorial Hospital</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Evans EM, Doctor RJ, Gage BF, Hotchkiss RS, Fuller BM, Drewry AM. The Association of Fever and Antipyretic Medication With Outcomes in Mechanically Ventilated Patients: A Cohort Study. Shock. 2019 Aug;52(2):152-159. doi: 10.1097/SHK.0000000000001368.</citation>
    <PMID>31058720</PMID>
  </reference>
  <reference>
    <citation>Drewry AM, Ablordeppey EA, Murray ET, Dalton CM, Fuller BM, Kollef MH, Hotchkiss RS. Monocyte Function and Clinical Outcomes in Febrile and Afebrile Patients With Severe Sepsis. Shock. 2018 Oct;50(4):381-387. doi: 10.1097/SHK.0000000000001083.</citation>
    <PMID>29240644</PMID>
  </reference>
  <reference>
    <citation>Drewry AM, Ablordeppey EA, Murray ET, Stoll CRT, Izadi SR, Dalton CM, Hardi AC, Fowler SA, Fuller BM, Colditz GA. Antipyretic Therapy in Critically Ill Septic Patients: A Systematic Review and Meta-Analysis. Crit Care Med. 2017 May;45(5):806-813. doi: 10.1097/CCM.0000000000002285.</citation>
    <PMID>28221185</PMID>
  </reference>
  <reference>
    <citation>Drewry AM, Fuller BM, Skrupky LP, Hotchkiss RS. The presence of hypothermia within 24 hours of sepsis diagnosis predicts persistent lymphopenia. Crit Care Med. 2015 Jun;43(6):1165-9. doi: 10.1097/CCM.0000000000000940.</citation>
    <PMID>25793436</PMID>
  </reference>
  <reference>
    <citation>Drewry AM, Fuller BM, Bailey TC, Hotchkiss RS. Body temperature patterns as a predictor of hospital-acquired sepsis in afebrile adult intensive care unit patients: a case-control study. Crit Care. 2013 Sep 12;17(5):R200. doi: 10.1186/cc12894.</citation>
    <PMID>24028682</PMID>
  </reference>
  <reference>
    <citation>Drewry AM, Hotchkiss R, Kulstad E. Response to &quot;Body temperature correlates with mortality in COVID-19 patients&quot;. Crit Care. 2020 Jul 24;24(1):460. doi: 10.1186/s13054-020-03186-w. No abstract available.</citation>
    <PMID>32709253</PMID>
  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 29, 2020</study_first_submitted>
  <study_first_submitted_qc>July 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <results_first_submitted>February 8, 2023</results_first_submitted>
  <results_first_submitted_qc>February 8, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">March 9, 2023</results_first_posted>
  <last_update_submitted>February 8, 2023</last_update_submitted>
  <last_update_submitted_qc>February 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sharp HealthCare</investigator_affiliation>
    <investigator_full_name>David Willms, MD</investigator_full_name>
    <investigator_title>Director, Clinical Care Services</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <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>March 2, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/67/NCT04494867/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Core Warming</title>
          <description>Patients assigned to receive the Attune Medical Esophageal Heat Transfer Device (EnsoETM) and undergo core warming&#xD;
Core Warming: Esophageal heat transfer device will be set to 42°C temperature after initial placement, and maintained at 42°C for the duration of treatment.</description>
        </group>
        <group group_id="P2">
          <title>Standard of Care</title>
          <description>Patients assigned to receive standard temperature management and treatment&#xD;
Standard of Care: Standard temperature management and treatment</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Patients who were randomized and received either core warming treatment or standard of care treatment. Does not include patients were randomized and withdrawn from study prior to receiving treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>Core Warming</title>
          <description>Patients who received the Attune Medical Esophageal Heat Transfer Device (EnsoETM) and undergo core warming&#xD;
Core Warming: Esophageal heat transfer device will be set to 42°C temperature after initial placement, and maintained at 42°C for the duration of treatment.</description>
        </group>
        <group group_id="B2">
          <title>Standard of Care</title>
          <description>Patients who received standard temperature management and treatment&#xD;
Standard of Care: Standard temperature management and treatment</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="9"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="19"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.7" spread="15.1"/>
                    <measurement group_id="B2" value="59.4" spread="10.3"/>
                    <measurement group_id="B3" value="60.5" spread="12.5"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Time to Enrollment</title>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.4" spread="13.1"/>
                    <measurement group_id="B2" value="9.1" spread="11.8"/>
                    <measurement group_id="B3" value="9.3" spread="12.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>meters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.623" spread="0.104"/>
                    <measurement group_id="B2" value="1.687" spread="0.098"/>
                    <measurement group_id="B3" value="1.66" spread="0.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kilograms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="94.8" spread="23.5"/>
                    <measurement group_id="B2" value="95.2" spread="14.2"/>
                    <measurement group_id="B3" value="95.1" spread="18.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35.8" spread="7.8"/>
                    <measurement group_id="B2" value="33.4" spread="3.4"/>
                    <measurement group_id="B3" value="34.5" spread="5.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Tobacco Usage</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethanol Usage</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-Existing Cardiovascular Condition</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-Existing Respiratory Condition at Baseline</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-Existing Hepatic Condition</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-Existing Gastrointestinal Condition</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-Existing Genitourinary Condition at Baseline</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-Existing Endocrine Condition</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-Existing Hematologic Condition</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-Existing Musculoskeletal Condition</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-Existing Neoplastic Condition</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-Existing Neurologic Condition</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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>Pre-Existing Psychiatric Condition</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-Existing Immunologic Condition</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-Existing Dermatologic Condition</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-Existing HEENT Condition</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Other Pre-Existing Condition</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Allergies</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Cycle Threshold</title>
          <units>Cycles</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31.7" spread="1.6"/>
                    <measurement group_id="B2" value="27.1" spread="1.45"/>
                    <measurement group_id="B3" value="29.1" spread="4.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>PaO2/FiO2 Ratio</title>
        <description>Determine the change in PaO2/FiO2 ratio at 0, 24, 48, and 72 hours after implementation of core warming of ventilated patients, and compare this change to patients undergoing standard care.</description>
        <time_frame>0, 24, 48, and 72 hours after initiation of core warming</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Core Warming</title>
            <description>Patients who received the Attune Medical Esophageal Heat Transfer Device (EnsoETM) and undergo core warming&#xD;
Core Warming: Esophageal heat transfer device will be set to 42°C temperature after initial placement, and maintained at 42°C for the duration of treatment.</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Patients who received standard temperature management and treatment&#xD;
Standard of Care: Standard temperature management and treatment</description>
          </group>
        </group_list>
        <measure>
          <title>PaO2/FiO2 Ratio</title>
          <description>Determine the change in PaO2/FiO2 ratio at 0, 24, 48, and 72 hours after implementation of core warming of ventilated patients, and compare this change to patients undergoing standard care.</description>
          <units>Ratio</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>0-hour timepoint</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="119.1435" spread="11.57574"/>
                    <measurement group_id="O2" value="164.789" spread="19.42075"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>24-hour timepoint</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="130.0138" spread="17.01536"/>
                    <measurement group_id="O2" value="154.9758" spread="21.10532"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>48-hour timepoint</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="158.2389" spread="19.43118"/>
                    <measurement group_id="O2" value="196.7167" spread="30.56792"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72-hour timepoint</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="134.3884" spread="13.41839"/>
                    <measurement group_id="O2" value="196.9593" spread="32.0182"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cycle Threshold at 72-hours</title>
        <description>Determine the change cycle threshold after implementation of core warming of ventilated patients, and compare this change to patients undergoing standard care.</description>
        <time_frame>72 hours after initiation of core warming</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Core Warming</title>
            <description>Patients who received the Attune Medical Esophageal Heat Transfer Device (EnsoETM) and undergo core warming&#xD;
Core Warming: Esophageal heat transfer device will be set to 42°C temperature after initial placement, and maintained at 42°C for the duration of treatment.</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Patients who received standard temperature management and treatment&#xD;
Standard of Care: Standard temperature management and treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Cycle Threshold at 72-hours</title>
          <description>Determine the change cycle threshold after implementation of core warming of ventilated patients, and compare this change to patients undergoing standard care.</description>
          <units>Cycles</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.4" spread="3.2"/>
                    <measurement group_id="O2" value="30.8" spread="6.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ventilator-Free Days</title>
        <description>Measure the impact of core warming on duration of mechanical ventilation.</description>
        <time_frame>Initiation of Core Warming Until Patient Weaned Off Mechanical Ventilation</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Core Warming</title>
            <description>Patients who received the Attune Medical Esophageal Heat Transfer Device (EnsoETM) and undergo core warming&#xD;
Core Warming: Esophageal heat transfer device will be set to 42°C temperature after initial placement, and maintained at 42°C for the duration of treatment.</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Patients who received standard temperature management and treatment&#xD;
Standard of Care: Standard temperature management and treatment</description>
          </group>
        </group_list>
        <measure>
          <title>Ventilator-Free Days</title>
          <description>Measure the impact of core warming on duration of mechanical ventilation.</description>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.8" spread="10.2"/>
                    <measurement group_id="O2" value="11.9" spread="12.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>30-Day Mortality</title>
        <description>Determine impact of core warming on patient mortality.</description>
        <time_frame>30 days after initiation of core warming</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Core Warming</title>
            <description>Patients who received the Attune Medical Esophageal Heat Transfer Device (EnsoETM) and undergo core warming&#xD;
Core Warming: Esophageal heat transfer device will be set to 42°C temperature after initial placement, and maintained at 42°C for the duration of treatment.</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care</title>
            <description>Patients who received standard temperature management and treatment&#xD;
Standard of Care: Standard temperature management and treatment</description>
          </group>
        </group_list>
        <measure>
          <title>30-Day Mortality</title>
          <description>Determine impact of core warming on patient mortality.</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="9"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Until 30 days post randomization or until hospital discharge</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Core Warming</title>
          <description>Patients who received the Attune Medical Esophageal Heat Transfer Device (EnsoETM) and undergo core warming&#xD;
Core Warming: Esophageal heat transfer device will be set to 42°C temperature after initial placement, and maintained at 42°C for the duration of treatment.</description>
        </group>
        <group group_id="E2">
          <title>Standard of Care</title>
          <description>Patients who received standard temperature management and treatment&#xD;
Standard of Care: Standard temperature management and treatment</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="2" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>MSSA Bacteremia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Stenotrophomonas maltophilia pneumonia and bacteremia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <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>Worsening of bilateral upper/lower extremity weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>anemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>elevated eosinophils</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>heparin-induced thrombocytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>elevated PTT</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>epistaxis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>leukopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>elevated RDW</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>tachycardia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>premature atrial contractions</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>elevated troponin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>aortic valve stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>PTH intact</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>stool positive for occult blood</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>ileus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>duodenal ulcers</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>elevated liver function tests</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>hepatic steatosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>hyperammonia cholestasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>elevated D-dimer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>elevated procalcitonin</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>toxic vacuoles</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>leukocytosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>fungal infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>E. coli pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>pseudomonas aeruginosa pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>E. coli bacteremia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>penile skin yeast infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>septic shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>bacterial superinfection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Klebsiella pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>mastoiditis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>tinea corpus under pannus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>enterobacter penumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>hypertriglyceridemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>hypernatremia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>azotemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>mild respiratory alkalosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>hyperglycemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>toxic metabolic encephalopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>low phosphorous level</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>hypomagnesemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>elevated BUN</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>supraglottic edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>dysphagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>elevated CA-125 tumor marker</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>elevated carcino-embyonic antigen</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>delirium</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>stammering</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>head tremor</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>acute encephalopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>tongue deviation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>adrenal insufficiency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>acute kidney injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>acute tubular necrosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>tracheobronchitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>pneumothorax</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>tracheostomy leak</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>tracheobronchomalacia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>possible herpes stomatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>tracheostomy wound infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>femoral DVT</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>anasarca</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Erik Kulstad, MD</name_or_title>
      <organization>Attune Medical</organization>
      <phone>+1-708-651-0736</phone>
      <email>ekulstad@gmail.com</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/NCT04494867
org study id: COVID-19 Core Warming
nct id: NCT04494867
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
The purpose of the proposed pilot study is to determine if core warming improves respiratory
      physiology of mechanically ventilated patients with COVID-19, allowing earlier weaning from
      ventilation, and greater overall survival.
This is a small scale pilot study to evaluate if core warming improves respiratory physiology
      of mechanically ventilated patients with COVID-19, allowing earlier weaning from ventilation,
      and greater overall survival. This prospective, randomized study will include 20 patients
      diagnosed with COVID-19, and undergoing mechanical ventilation for the treatment of
      respiratory failure. Patients will be randomized in a 1:1 fashion with 10 patients (Group A)
      randomized to undergo core warming, and the other 10 patients (Group B) serving as the
      control group who will not have the ensoETM device used. Patients randomized to Group A will
      have core warming initiated in the ICU or other clinical environment in which they are being
      treated after enrollment and provision of informed consent from appropriate surrogate or
      legally authorized representative.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: PaO2/FiO2 Ratio
time frame: 0, 24, 48, and 72 hours after initiation of core warming
description: Determine the change in PaO2/FiO2 ratio at 0, 24, 48, and 72 hours after implementation of core warming of ventilated patients, and compare this change to patients undergoing standard care.
measure: Cycle Threshold at 72-hours
time frame: 72 hours after initiation of core warming
description: Determine the change cycle threshold after implementation of core warming of ventilated patients, and compare this change to patients undergoing standard care.
measure: Ventilator-Free Days
time frame: Initiation of Core Warming Until Patient Weaned Off Mechanical Ventilation
description: Measure the impact of core warming on duration of mechanical ventilation.
measure: 30-Day Mortality
time frame: 30 days after initiation of core warming
description: Determine impact of core warming on patient mortality.
arm group label: Core warming
arm group type: Experimental
description: Patients receive the Attune Medical Esophageal Heat Transfer Device (EnsoETM) and undergo core warming
arm group label: Standard of Care
arm group type: Active Comparator
description: Patients receive standard temperature management and treatment
intervention type: Device
intervention name: Core Warming
description: Esophageal heat transfer device will be set to 42°C temperature after initial placement, and maintained at 42°C for the duration of treatment.
arm group label: Core warming
other name: EnsoETM
intervention type: Other
intervention name: Standard of Care
description: Standard temperature management and treatment
arm group label: Standard of Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David Willms, MD
role: Principal Investigator
affiliation: Sharp HealthCare
last name: Ahmed Salem, MD
role: Principal Investigator
affiliation: Sharp HealthCare
facility: 
country: United States
citation: Evans EM, Doctor RJ, Gage BF, Hotchkiss RS, Fuller BM, Drewry AM. The Association of Fever and Antipyretic Medication With Outcomes in Mechanically Ventilated Patients: A Cohort Study. Shock. 2019 Aug;52(2):152-159. doi: 10.1097/SHK.0000000000001368.
PMID: 31058720
citation: Drewry AM, Ablordeppey EA, Murray ET, Dalton CM, Fuller BM, Kollef MH, Hotchkiss RS. Monocyte Function and Clinical Outcomes in Febrile and Afebrile Patients With Severe Sepsis. Shock. 2018 Oct;50(4):381-387. doi: 10.1097/SHK.0000000000001083.
PMID: 29240644
citation: Drewry AM, Ablordeppey EA, Murray ET, Stoll CRT, Izadi SR, Dalton CM, Hardi AC, Fowler SA, Fuller BM, Colditz GA. Antipyretic Therapy in Critically Ill Septic Patients: A Systematic Review and Meta-Analysis. Crit Care Med. 2017 May;45(5):806-813. doi: 10.1097/CCM.0000000000002285.
PMID: 28221185
citation: Drewry AM, Fuller BM, Skrupky LP, Hotchkiss RS. The presence of hypothermia within 24 hours of sepsis diagnosis predicts persistent lymphopenia. Crit Care Med. 2015 Jun;43(6):1165-9. doi: 10.1097/CCM.0000000000000940.
PMID: 25793436
citation: Drewry AM, Fuller BM, Bailey TC, Hotchkiss RS. Body temperature patterns as a predictor of hospital-acquired sepsis in afebrile adult intensive care unit patients: a case-control study. Crit Care. 2013 Sep 12;17(5):R200. doi: 10.1186/cc12894.
PMID: 24028682
citation: Drewry AM, Hotchkiss R, Kulstad E. Response to "Body temperature correlates with mortality in COVID-19 patients". Crit Care. 2020 Jul 24;24(1):460. doi: 10.1186/s13054-020-03186-w. No abstract available.
PMID: 32709253
responsible party type: Principal Investigator
investigator affiliation: Sharp HealthCare
investigator full name: David Willms, MD
investigator title: Director, Clinical Care Services
mesh term: COVID-19
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 