<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/NCT04424797</url>
  </required_header>
  <id_info>
    <org_study_id>20-6034</org_study_id>
    <nct_id>NCT04424797</nct_id>
  </id_info>
  <brief_title>Prone Positioning on Admission for Hospitalized COVID-19 Pneumonia Protocol</brief_title>
  <official_title>Prone Positioning on Admission for Hospitalized COVID-19 Pneumonia Protocol</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Poudre Valley Health System</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Poudre Valley Health System</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A pilot study to investigate the effects of the prone positioning (PP) on hospital patients&#xD;
      diagnosed with COVID-19 pneumonia.&#xD;
&#xD;
      Investigators that early self-proning may prevent intubation and improve mortality in&#xD;
      patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2).&#xD;
&#xD;
      Up to 100 participants with a primary diagnosis of confirmed COVID-19 pneumonia will be&#xD;
      enrolled to the study.&#xD;
&#xD;
      All participants will be screened and those that meet inclusion and exclusion criteria will&#xD;
      be enrolled to one of two groups: one with prone positioning (on the belly) and the other&#xD;
      with standard supine positioning (on the back). The patient and nursing staff will monitor&#xD;
      times spent in various positions.&#xD;
&#xD;
      Outcome measures include incidence of intubation, max oxygen requirements, length of hospital&#xD;
      stay, ventilator-free days, worsening of oxygenation saturation, and mortality.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In hypoxic respiratory failure, placing patients in the prone position improves ventilation&#xD;
      to perfusion matching, alveolar recruitment, and alveolar to arterial oxygen gradients.&#xD;
      Specifically, in Acute Respiratory Distress Syndrome ARDS, proning intubated patients&#xD;
      improves overall mortality. With the emergence of SARS-COV-2, hospitals around the world have&#xD;
      seen a marked increase in patients with acute hypoxic respiratory failure and ARDS. This&#xD;
      surge in cases has prompted a search for more effective strategies to reduce intubation and&#xD;
      improve patient morbidity and mortality. One such strategy is that of voluntary proning, in&#xD;
      which awake patients are instructed to prone themselves (Early PP With High Flow Nasal&#xD;
      Cannula (HFNC) Versus HFNC in COVID-19 Induced Moderate to Severe ARDS) (COVID-19&#xD;
      smArtphone-based Trial of Non-ICU Admission Prone Positioning (CATNAP)).&#xD;
&#xD;
      This trial proposes a voluntary proning strategy in patients admitted to the hospital, not&#xD;
      yet requiring mechanical ventilation. Given the clear evidence that proning improves outcomes&#xD;
      in ARDS, investigators hypothesize that early, voluntary self-proning may prevent intubation&#xD;
      and improve mortality in patients with SARS-COV-2.&#xD;
&#xD;
      Methods&#xD;
&#xD;
      This is a pilot study of up to 100 participants at UCHealth facilities.&#xD;
&#xD;
      Patients will be assessed if they can self prone safely and be assessed against inclusion and&#xD;
      exclusion criteria within 12 hours of admission and randomized to either prone or supine&#xD;
      positioning. Baseline labs will be measured and all participants will be monitored&#xD;
      continuously via pulse oximetry.&#xD;
&#xD;
      The Standard Supine Control Group will utilize standard oxygen (O2) device in supine position&#xD;
      at approximately 30-60 degrees to target peripheral capillary oxygen saturation (SpO2) &gt;90%&#xD;
      and the participant or nurse will document time in non-supine position.&#xD;
&#xD;
      The Prone Experimental Group will position patient in approximately 15-degree reverse&#xD;
      trendelenburg and prone using pillows for comfort. The participant will be asked to rotate to&#xD;
      prone positioning every 2 hours while awake and encourage to sleep prone overnight as&#xD;
      possible with a goal of 10-12 hours daily. Patient to log all time prone.&#xD;
&#xD;
      Treatment Failure may occur and termination of Intermittent Prone Positioning will occur.&#xD;
      This is defined as respiratory distress or a decrease in O2 saturations &lt;90% for more than 2&#xD;
      minutes as determined by bedside nursing or per virtual pulse oximetry monitoring&#xD;
      notifications during the study on two consecutive occasions. The participant will be returned&#xD;
      to supine positioning and follow standard supine oxygenation. The participant can be&#xD;
      re-challenged in the prone position after the participant stabilizes for 2 hours. The&#xD;
      participant can also choose to stop proning and would be considered a treatment failures.&#xD;
&#xD;
      Statistical Analysis and Sample Size In New York City the intubation rate has been reported&#xD;
      at 1/3 of COVID-19 positive patients admitted to the hospital. The table below shows the&#xD;
      sample size needed for a binomial outcome of intubation when 50% of the sample is randomized&#xD;
      to Prone Positioning (PP):&#xD;
&#xD;
      Alpha 0.05 0.05 0.05 0.05 Beta 0.80 0.80 0.80 0.80 Probability of intubation with PP 0.05&#xD;
      0.10 0.15 0.20 Probability of intubation 0.33 0.33 0.33 0.33 Proportion receiving PP 0.50&#xD;
      0.50 0.50 0.50 Sample size 33 39 56 97&#xD;
&#xD;
      Expecting a 13% decrease in intubations with the prone position, investigators will use a&#xD;
      sample size of N = 100 (50 per group) in order to have 80% power with a two-sided alpha =&#xD;
      0.05 for logistic regression. ANCOVA will be used to evaluate continuous, secondary variables&#xD;
      in order to adjust for covariates. The study is powered for the primary outcome of intubation&#xD;
      or no intubation. No adjustments will be made for the secondary endpoints.&#xD;
&#xD;
      The investigators and statistician will validate the data and the study will be subject to&#xD;
      institutional quality assurance reviews.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 13, 2020</start_date>
  <completion_date type="Anticipated">July 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">July 31, 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>
    <intervention_model_description>Prone vs. Supine positioning</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of intubation</measure>
    <time_frame>Through study completion, an average of 6 days</time_frame>
    <description>Incidence of intubation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum oxygen requirement</measure>
    <time_frame>Through study completion, an average of 6 days</time_frame>
    <description>Measure of maximum oxygen requirements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of Stay</measure>
    <time_frame>Through study completion, an average of 6 days</time_frame>
    <description>Measured in days of hospitalization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilator-free days</measure>
    <time_frame>Through study completion, an average of 6 days</time_frame>
    <description>Measured in days not on a ventilator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment failure of prone positioning due to worsening SpO2 status while prone</measure>
    <time_frame>Through study completion, an average of 6 days</time_frame>
    <description>Whether or not the participant met treatment failure descriptions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>Through study completion, an average of 6 days</time_frame>
    <description>Whether or not the participant died while hospitalized</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Prone Positioning</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Prone positioning</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Supine Positioning</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Supine Positioning</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Prone Positioning</intervention_name>
    <description>Intervention is patient in prone positioning</description>
    <arm_group_label>Prone Positioning</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Supine Positioning</intervention_name>
    <description>Intervention is patient in supine positioning</description>
    <arm_group_label>Supine Positioning</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients admitted to the hospital floor with primary diagnosis of confirmed COVID-19&#xD;
             pneumonia and respiratory failure requiring greater than or equal to 2 Liters(L) Nasal&#xD;
             Cannula (NC) to maintain SpO2&gt;90%&#xD;
&#xD;
          -  Ability to independently change positions in bed&#xD;
&#xD;
          -  Able to tolerate prone positioning&#xD;
&#xD;
          -  Age greater than 18&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ICU admission on arrival&#xD;
&#xD;
          -  Respiratory distress requiring immediate intubation&#xD;
&#xD;
               -  Respiratory Rate(RR)&gt;35/min, accessory respiratory muscle use (ex. speaking in&#xD;
                  short sentences), signs of respiratory muscle fatigue, altered mental status, or&#xD;
                  inability to protect airway&#xD;
&#xD;
          -  Chest or facial trauma, pneumothorax or other contraindication to prone positioning&#xD;
             (i.e., spinal instability, recent abdominal surgery, pregnancy, etc)&#xD;
&#xD;
          -  Hemodynamically unstable&#xD;
&#xD;
               -  Heart Rate (HR)&gt;120 bpm, Systolic Blood Pressure (SBP)&lt;90 mmHg, Mean Arterial&#xD;
                  Pressure (MAP)&lt;65 mmHg or requirement for vasopressor&#xD;
&#xD;
          -  Nausea and vomiting&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Refusal or inability to tolerate initial prone positioning due to comfort&#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>Lucie Uncapher</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado Health</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sara Twombly, MACI CCRC</last_name>
    <phone>970-297-6188</phone>
    <email>sara.twombly@uchealth.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Adam Jaskowiak</last_name>
    <phone>970-624-1688</phone>
    <email>adam.jaskowiak@uchealth.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>UCHealth Poudre Valley Hospital</name>
      <address>
        <city>Fort Collins</city>
        <state>Colorado</state>
        <zip>80524</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Manager</last_name>
    </contact>
    <investigator>
      <last_name>Lucie Uncapher, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UCHealth Greeley Hospital</name>
      <address>
        <city>Greeley</city>
        <state>Colorado</state>
        <zip>80634</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Manager</last_name>
    </contact>
    <investigator>
      <last_name>Lucie Uncapher, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UCHealth Medical Center of the Rockies</name>
      <address>
        <city>Loveland</city>
        <state>Colorado</state>
        <zip>80538</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Research Manager</last_name>
    </contact>
    <investigator>
      <last_name>Lucie Uncapher, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>June 5, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>April 18, 2022</last_update_submitted>
  <last_update_submitted_qc>April 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Poudre Valley Health System</investigator_affiliation>
    <investigator_full_name>Lucie Uncapher</investigator_full_name>
    <investigator_title>Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Pneumonia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>May 9, 2023</submitted>
  </pending_results>
  <!-- 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/NCT04424797
org study id: 20-6034
nct id: NCT04424797
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A pilot study to investigate the effects of the prone positioning (PP) on hospital patients
      diagnosed with COVID-19 pneumonia.

      Investigators that early self-proning may prevent intubation and improve mortality in
      patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2).

      Up to 100 participants with a primary diagnosis of confirmed COVID-19 pneumonia will be
      enrolled to the study.

      All participants will be screened and those that meet inclusion and exclusion criteria will
      be enrolled to one of two groups: one with prone positioning (on the belly) and the other
      with standard supine positioning (on the back). The patient and nursing staff will monitor
      times spent in various positions.

      Outcome measures include incidence of intubation, max oxygen requirements, length of hospital
      stay, ventilator-free days, worsening of oxygenation saturation, and mortality.
In hypoxic respiratory failure, placing patients in the prone position improves ventilation
      to perfusion matching, alveolar recruitment, and alveolar to arterial oxygen gradients.
      Specifically, in Acute Respiratory Distress Syndrome ARDS, proning intubated patients
      improves overall mortality. With the emergence of SARS-COV-2, hospitals around the world have
      seen a marked increase in patients with acute hypoxic respiratory failure and ARDS. This
      surge in cases has prompted a search for more effective strategies to reduce intubation and
      improve patient morbidity and mortality. One such strategy is that of voluntary proning, in
      which awake patients are instructed to prone themselves (Early PP With High Flow Nasal
      Cannula (HFNC) Versus HFNC in COVID-19 Induced Moderate to Severe ARDS) (COVID-19
      smArtphone-based Trial of Non-ICU Admission Prone Positioning (CATNAP)).

      This trial proposes a voluntary proning strategy in patients admitted to the hospital, not
      yet requiring mechanical ventilation. Given the clear evidence that proning improves outcomes
      in ARDS, investigators hypothesize that early, voluntary self-proning may prevent intubation
      and improve mortality in patients with SARS-COV-2.

      Methods

      This is a pilot study of up to 100 participants at UCHealth facilities.

      Patients will be assessed if they can self prone safely and be assessed against inclusion and
      exclusion criteria within 12 hours of admission and randomized to either prone or supine
      positioning. Baseline labs will be measured and all participants will be monitored
      continuously via pulse oximetry.

      The Standard Supine Control Group will utilize standard oxygen (O2) device in supine position
      at approximately 30-60 degrees to target peripheral capillary oxygen saturation (SpO2) >90%
      and the participant or nurse will document time in non-supine position.

      The Prone Experimental Group will position patient in approximately 15-degree reverse
      trendelenburg and prone using pillows for comfort. The participant will be asked to rotate to
      prone positioning every 2 hours while awake and encourage to sleep prone overnight as
      possible with a goal of 10-12 hours daily. Patient to log all time prone.

      Treatment Failure may occur and termination of Intermittent Prone Positioning will occur.
      This is defined as respiratory distress or a decrease in O2 saturations <90% for more than 2
      minutes as determined by bedside nursing or per virtual pulse oximetry monitoring
      notifications during the study on two consecutive occasions. The participant will be returned
      to supine positioning and follow standard supine oxygenation. The participant can be
      re-challenged in the prone position after the participant stabilizes for 2 hours. The
      participant can also choose to stop proning and would be considered a treatment failures.

      Statistical Analysis and Sample Size In New York City the intubation rate has been reported
      at 1/3 of COVID-19 positive patients admitted to the hospital. The table below shows the
      sample size needed for a binomial outcome of intubation when 50% of the sample is randomized
      to Prone Positioning (PP):

      Alpha 0.05 0.05 0.05 0.05 Beta 0.80 0.80 0.80 0.80 Probability of intubation with PP 0.05
      0.10 0.15 0.20 Probability of intubation 0.33 0.33 0.33 0.33 Proportion receiving PP 0.50
      0.50 0.50 0.50 Sample size 33 39 56 97

      Expecting a 13% decrease in intubations with the prone position, investigators will use a
      sample size of N = 100 (50 per group) in order to have 80% power with a two-sided alpha =
      0.05 for logistic regression. ANCOVA will be used to evaluate continuous, secondary variables
      in order to adjust for covariates. The study is powered for the primary outcome of intubation
      or no intubation. No adjustments will be made for the secondary endpoints.

      The investigators and statistician will validate the data and the study will be subject to
      institutional quality assurance reviews.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prone vs. Supine positioning
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of intubation
time frame: Through study completion, an average of 6 days
description: Incidence of intubation
measure: Maximum oxygen requirement
time frame: Through study completion, an average of 6 days
description: Measure of maximum oxygen requirements
measure: Length of Stay
time frame: Through study completion, an average of 6 days
description: Measured in days of hospitalization
measure: Ventilator-free days
time frame: Through study completion, an average of 6 days
description: Measured in days not on a ventilator
measure: Treatment failure of prone positioning due to worsening SpO2 status while prone
time frame: Through study completion, an average of 6 days
description: Whether or not the participant met treatment failure descriptions
measure: Mortality
time frame: Through study completion, an average of 6 days
description: Whether or not the participant died while hospitalized
arm group label: Prone Positioning
arm group type: Experimental
description: Prone positioning
arm group label: Supine Positioning
arm group type: Other
description: Supine Positioning
intervention type: Other
intervention name: Prone Positioning
description: Intervention is patient in prone positioning
arm group label: Prone Positioning
intervention type: Other
intervention name: Supine Positioning
description: Intervention is patient in supine positioning
arm group label: Supine Positioning
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lucie Uncapher
role: Principal Investigator
affiliation: University of Colorado Health
last name: Sara Twombly, MACI CCRC
phone: 970-297-6188
email: sara.twombly@uchealth.org
last name: Adam Jaskowiak
phone: 970-624-1688
email: adam.jaskowiak@uchealth.org
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Poudre Valley Health System
investigator full name: Lucie Uncapher
investigator title: Investigator
mesh term: COVID-19
mesh term: Pneumonia
sharing ipd: No
submitted: May 9, 2023