<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/NCT04426344</url>
  </required_header>
  <id_info>
    <org_study_id>202005150</org_study_id>
    <nct_id>NCT04426344</nct_id>
  </id_info>
  <brief_title>Core Warming of COVID-19 Patients</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>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Washington University School of Medicine</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>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <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>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants will be randomized in a 1:1 fashion to core warming with the study device&#xD;
      (ensoETM) or to standard of care (standard temperature management and treatment). The device&#xD;
      will be used as indicated (for warming). Patient temperature measurement will be collected&#xD;
      for both the core warming and standard of care arms during the study period (72 hours).&#xD;
&#xD;
      Core warming will be performed using standard technique per instructions for use for the&#xD;
      esophageal heat transfer device. The esophageal heat transfer device will be set to 42°C&#xD;
      temperature after initial placement, and maintained at 42°C for the duration of treatment. It&#xD;
      is expected that patient temperature will increase from baseline by 1°C to 2°C, but due to&#xD;
      ongoing heat loss from the patient, the expected maximum patient temperature is below 39°C.&#xD;
      The time course of illness of COVID-19 is such that most patients no longer have fever by the&#xD;
      time of mechanical ventilation. If patient temperature increases above this range and reaches&#xD;
      39.8°C, the device will be set to an operating temperature of 40°C, thereby preventing any&#xD;
      further increase in patient temperature (ambient heat loss precludes patient from reaching&#xD;
      device operating temperature).&#xD;
&#xD;
      Control group patients will be managed as per standard of care currently utilized in the ICU,&#xD;
      which will include the use of other methods of temperature management as warranted. This&#xD;
      would include warming with a forced air blanket only in hypothermic patients (core&#xD;
      temperature &lt; 36°C) or antipyretic therapy for febrile patients, as requested by the treating&#xD;
      physician. Episodes of hypothermia are infrequent and transient in this population, and the&#xD;
      current standard of care generally utilizes a permissive approach to fever (allowing patients&#xD;
      to remain mildly febrile) which will continue in the control group without modification (no&#xD;
      intentional elevation of temperature will be provided in the control group).&#xD;
&#xD;
      Follow up data will be collected at 1 month following enrollment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Internal decision&#xD;
  </why_stopped>
  <start_date type="Anticipated">October 2020</start_date>
  <completion_date type="Anticipated">December 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2020</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>
    <intervention_model_description>Randomized, single center pilot study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Due to the nature of this study, the physicians will not be blinded to the randomization assignment, however participants will be blinded. Once a subject is randomized, the research team will receive the randomization assignment (core warming or standard of care) and proceed with the procedures per the assignment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Viral load measured in tracheal aspirate 72 hours after initiation of core warming</measure>
    <time_frame>72 hours</time_frame>
    <description>This endpoint will be compared between patients receiving core warming and those randomized to undergo standard care (standard temperature management, with or without antipyretics as needed) in order to determine an initial estimate of effect size and provide data from which to design adequately powered investigation and apply appropriate statistical testing.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PaO2/FiO2 ratio 72 hours after initiation of core warming</measure>
    <time_frame>72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of mechanical ventilation</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>COVID 19</condition>
  <arm_group>
    <arm_group_label>Group A - core warming</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized to Group A will have core warming with the ensoETM device initiated in the ICU or other clinical environment in which they are being treated. The device will be used as indicated (for warming). Patient temperature measurement will be collected for both the core warming and standard of care arms during the study period (72 hours).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B - Control Group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Group B is serving as the control group who will not have the ensoETM device used.Control group patients will be managed as per standard of care currently utilized in the ICU, which will include the use of other methods of temperature management as warranted. This would include warming with a forced air blanket only in hypothermic patients (core temperature &lt; 36°C) or antipyretic therapy for febrile patients, as requested by the treating physician.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>ensoETM device</intervention_name>
    <description>Core warming will be performed using standard technique per instructions for use for the esophageal heat transfer device. The esophageal heat transfer device will be set to 42°C temperature after initial placement, and maintained at 42°C for the duration of treatment. It is expected that patient temperature will increase from baseline by 1°C to 2°C, but due to ongoing heat loss from the patient, the expected maximum patient temperature is below 39°C. The time course of illness of COVID-19 is such that most patients no longer have fever by the time of mechanical ventilation.[41] If patient temperature increases above this range and reaches 39.8°C, the device will be set to an operating temperature of 40°C, thereby preventing any further increase in patient temperature (ambient heat loss precludes patient from reaching device operating temperature).</description>
    <arm_group_label>Group A - core warming</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients above the age of 18 years old.&#xD;
&#xD;
          2. Patients with a diagnosis of COVID-19 on mechanical ventilation.&#xD;
&#xD;
          3. Patient maximum baseline temperature (within previous 12 hours) &lt; 38.3°C.&#xD;
&#xD;
          4. 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;
          1. Patients without surrogate or legally authorized representative able to provide&#xD;
             informed consent.&#xD;
&#xD;
          2. Patients with contraindication to core warming using an esophageal core warming&#xD;
             device.&#xD;
&#xD;
          3. Patients known to be pregnant.&#xD;
&#xD;
          4. Patients with &lt;40 kg of body mass.&#xD;
&#xD;
          5. Patients with DNR status.&#xD;
&#xD;
          6. Patients with acute stroke, post-cardiac arrest, or multiple sclerosis.&#xD;
&#xD;
          7. Patients with history of esophageal disease&#xD;
&#xD;
          8. Patients with a baseline epinephrine dose greater than 0.6 mcg/kg/min&#xD;
&#xD;
          9. Patients with atrial fibrillation, atrial flutter, or other multifocal atrial&#xD;
             tachycardia with a heart rate greater than 110 beats per minute.&#xD;
&#xD;
         10. Patients on 0.2 mcg/kg/min or more of norepinephrine&#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>Anne Drewry, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington Univeristy School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Barnes-Jewish Hospital</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>October 14, 2020</last_update_submitted>
  <last_update_submitted_qc>October 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID 19</keyword>
  <keyword>Warming</keyword>
  <keyword>Mechanical ventilation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04426344
org study id: 202005150
nct id: NCT04426344
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
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.
Participants will be randomized in a 1:1 fashion to core warming with the study device
      (ensoETM) or to standard of care (standard temperature management and treatment). The device
      will be used as indicated (for warming). Patient temperature measurement will be collected
      for both the core warming and standard of care arms during the study period (72 hours).

      Core warming will be performed using standard technique per instructions for use for the
      esophageal heat transfer device. The esophageal heat transfer device will be set to 42°C
      temperature after initial placement, and maintained at 42°C for the duration of treatment. It
      is expected that patient temperature will increase from baseline by 1°C to 2°C, but due to
      ongoing heat loss from the patient, the expected maximum patient temperature is below 39°C.
      The time course of illness of COVID-19 is such that most patients no longer have fever by the
      time of mechanical ventilation. If patient temperature increases above this range and reaches
      39.8°C, the device will be set to an operating temperature of 40°C, thereby preventing any
      further increase in patient temperature (ambient heat loss precludes patient from reaching
      device operating temperature).

      Control group patients will be managed as per standard of care currently utilized in the ICU,
      which will include the use of other methods of temperature management as warranted. This
      would include warming with a forced air blanket only in hypothermic patients (core
      temperature < 36°C) or antipyretic therapy for febrile patients, as requested by the treating
      physician. Episodes of hypothermia are infrequent and transient in this population, and the
      current standard of care generally utilizes a permissive approach to fever (allowing patients
      to remain mildly febrile) which will continue in the control group without modification (no
      intentional elevation of temperature will be provided in the control group).

      Follow up data will be collected at 1 month following enrollment.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized, single center pilot study
primary purpose: Treatment
masking: Single (Participant)
masking description: Due to the nature of this study, the physicians will not be blinded to the randomization assignment, however participants will be blinded. Once a subject is randomized, the research team will receive the randomization assignment (core warming or standard of care) and proceed with the procedures per the assignment.
measure: Viral load measured in tracheal aspirate 72 hours after initiation of core warming
time frame: 72 hours
description: This endpoint will be compared between patients receiving core warming and those randomized to undergo standard care (standard temperature management, with or without antipyretics as needed) in order to determine an initial estimate of effect size and provide data from which to design adequately powered investigation and apply appropriate statistical testing.
measure: PaO2/FiO2 ratio 72 hours after initiation of core warming
time frame: 72 hours
measure: Duration of mechanical ventilation
time frame: 30 days
arm group label: Group A - core warming
arm group type: Experimental
description: Patients randomized to Group A will have core warming with the ensoETM device initiated in the ICU or other clinical environment in which they are being treated. The device will be used as indicated (for warming). Patient temperature measurement will be collected for both the core warming and standard of care arms during the study period (72 hours).
arm group label: Group B - Control Group
arm group type: No Intervention
description: Group B is serving as the control group who will not have the ensoETM device used.Control group patients will be managed as per standard of care currently utilized in the ICU, which will include the use of other methods of temperature management as warranted. This would include warming with a forced air blanket only in hypothermic patients (core temperature < 36°C) or antipyretic therapy for febrile patients, as requested by the treating physician.
intervention type: Device
intervention name: ensoETM device
description: Core warming will be performed using standard technique per instructions for use for the esophageal heat transfer device. The esophageal heat transfer device will be set to 42°C temperature after initial placement, and maintained at 42°C for the duration of treatment. It is expected that patient temperature will increase from baseline by 1°C to 2°C, but due to ongoing heat loss from the patient, the expected maximum patient temperature is below 39°C. The time course of illness of COVID-19 is such that most patients no longer have fever by the time of mechanical ventilation.[41] If patient temperature increases above this range and reaches 39.8°C, the device will be set to an operating temperature of 40°C, thereby preventing any further increase in patient temperature (ambient heat loss precludes patient from reaching device operating temperature).
arm group label: Group A - core warming
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anne Drewry, MD
role: Principal Investigator
affiliation: Washington Univeristy School of Medicine
facility: 
country: United States
responsible party type: Sponsor
mesh term: COVID-19