<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/NCT04477655</url>
  </required_header>
  <id_info>
    <org_study_id>048/20</org_study_id>
    <nct_id>NCT04477655</nct_id>
  </id_info>
  <brief_title>Prone Positioning in Non-intubated Patients With COVID-19 Associated Acute Respiratory Failure</brief_title>
  <acronym>PRO-CARF</acronym>
  <official_title>Prone Positioning in Non-intubated Patients With Severe COVID-19: a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Civil de Guadalajara</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital Civil de Guadalajara</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Besides protective ventilation with low tidal volumes, prone positioning is a proven&#xD;
      intervention to decrease mortality in mechanically ventilated patients with moderate-severe&#xD;
      acute respiratory distress syndrome. However, the evidence of this strategy in awake&#xD;
      non-intubated patients is scarce. The investigators will perform a randomized controlled&#xD;
      trial to define if prone positioning can reduce the requirement of mechanical ventilation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Despite ongoing trials of antivirals and immunomodulatory therapies against COVID-19, the&#xD;
      treatment of moderate/severe disease is mainly supportive, including oxygen therapy and&#xD;
      invasive mechanical ventilation when impending respiratory failure is established. Moreover,&#xD;
      the associated mortality among mechanically intubated patients is overwhelmingly high. Prone&#xD;
      position relieves the dependent lung regions from the compressive forces of the mediastinum's&#xD;
      weight, leading to homogenization of the gas:tissue ratio between ventral and dorsal lung&#xD;
      regions. According to a few case series, and observational non-randomized studies with small&#xD;
      sample sizes, there is a consistent improvement in oxygenation in COVID-19 patients during&#xD;
      prone positioning, however there are no clinical evidence that this improvement is associated&#xD;
      with a decrease in the risk of invasive mechanical ventilation. Considering that prone&#xD;
      positioning is a low cost, low risk and widely available therapy, more high quality evidence&#xD;
      is needed, to determine if the benefits of prone positioning in awake patients also include a&#xD;
      lower requirement of mechanical ventilation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 3, 2020</start_date>
  <completion_date type="Actual">January 26, 2021</completion_date>
  <primary_completion_date type="Actual">January 26, 2021</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>Intubation rate</measure>
    <time_frame>28 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total hours of prone position at day</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total number of prone sessions at day</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hours of the longest prone session each day</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in oxygenation 1-hour after first prone session</measure>
    <time_frame>1 hour</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the ROX-index 1-hour after first prone session</measure>
    <time_frame>1 hour</time_frame>
    <description>The change in the Ratio of Oxygen saturation to respiratory rate (ROX-index)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total days of prone positioning therapy</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse effects of prone positioning therapy</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mechanical ventilation days</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intensive care unit length of stay</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital length of stay</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital mortality</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">430</enrollment>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>Standard oxygen therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oxygen therapy through high flow nasal cannula (HFNC). Continuous monitoring of vital signs. Inspired fraction of oxygen will be titrated to maintain a capillary saturation of ≥92%. Prone positioning will be allowed as a rescue therapy.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Awake prone positioning</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oxygen therapy through high flow nasal cannula (HFNC). Patients will be asked to remain in prone position throughout the day as long as possible, with breaks according to tolerance. Pillows will be offered for maximizing comfort at chest, pelvis and knees. Monitoring of vital signs will not be suspended. Inspired fraction of oxygen will be titrated to maintain a capillary saturation of ≥92%.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Awake prone positioning</intervention_name>
    <description>Patients will be asked to remain in prone position or lateral decubitus throughout the day as long as possible.</description>
    <arm_group_label>Awake prone positioning</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Standard oxygen therapy</intervention_name>
    <description>Oxygen therapy through high flow nasal cannula (HFNC). Inspired fraction of oxygen will be titrated to maintain a capillary saturation of ≥92%</description>
    <arm_group_label>Standard oxygen therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients with confirmed COVID-19, and requirement of a fraction of inspired&#xD;
             oxygen (FiO2) ≥30% through high-flow nasal cannula (HFNC) to maintain a capillary&#xD;
             saturation of ≥90%&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Less than 18 years-old&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Patients with immediate need of invasive mechanical ventilation&#xD;
&#xD;
          -  Contraindications for prone positioning therapy&#xD;
&#xD;
          -  Do-not-resuscitate or do-not-intubate order&#xD;
&#xD;
          -  Refusal of the patient or decision maker to enroll in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Miguel Ibarra-Estrada</last_name>
    <role>Principal Investigator</role>
    <affiliation>Investigator</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Civil Fray Antonio Alcalde</name>
      <address>
        <city>Guadalajara</city>
        <state>Jalisco</state>
        <zip>44280</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General de Occidente</name>
      <address>
        <city>Guadalajara</city>
        <state>Jalisco</state>
        <zip>45170</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>April 12, 2021</last_update_submitted>
  <last_update_submitted_qc>April 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 13, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Civil de Guadalajara</investigator_affiliation>
    <investigator_full_name>Miguel Á Ibarra-Estrada</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>Severe</keyword>
  <keyword>Prone positioning</keyword>
  <keyword>High-flow nasal cannula</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04477655
org study id: 048/20
nct id: NCT04477655
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Besides protective ventilation with low tidal volumes, prone positioning is a proven
      intervention to decrease mortality in mechanically ventilated patients with moderate-severe
      acute respiratory distress syndrome. However, the evidence of this strategy in awake
      non-intubated patients is scarce. The investigators will perform a randomized controlled
      trial to define if prone positioning can reduce the requirement of mechanical ventilation.
Despite ongoing trials of antivirals and immunomodulatory therapies against COVID-19, the
      treatment of moderate/severe disease is mainly supportive, including oxygen therapy and
      invasive mechanical ventilation when impending respiratory failure is established. Moreover,
      the associated mortality among mechanically intubated patients is overwhelmingly high. Prone
      position relieves the dependent lung regions from the compressive forces of the mediastinum's
      weight, leading to homogenization of the gas:tissue ratio between ventral and dorsal lung
      regions. According to a few case series, and observational non-randomized studies with small
      sample sizes, there is a consistent improvement in oxygenation in COVID-19 patients during
      prone positioning, however there are no clinical evidence that this improvement is associated
      with a decrease in the risk of invasive mechanical ventilation. Considering that prone
      positioning is a low cost, low risk and widely available therapy, more high quality evidence
      is needed, to determine if the benefits of prone positioning in awake patients also include a
      lower requirement of mechanical ventilation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Intubation rate
time frame: 28 days
measure: Total hours of prone position at day
time frame: 28 days
measure: Total number of prone sessions at day
time frame: 28 days
measure: Hours of the longest prone session each day
time frame: 28 days
measure: Change in oxygenation 1-hour after first prone session
time frame: 1 hour
measure: Change in the ROX-index 1-hour after first prone session
time frame: 1 hour
description: The change in the Ratio of Oxygen saturation to respiratory rate (ROX-index)
measure: Total days of prone positioning therapy
time frame: 28 days
measure: Adverse effects of prone positioning therapy
time frame: 28 days
measure: Mechanical ventilation days
time frame: 28 days
measure: Intensive care unit length of stay
time frame: 28 days
measure: Hospital length of stay
time frame: 28 days
measure: Hospital mortality
time frame: 28 days
arm group label: Standard oxygen therapy
arm group type: Active Comparator
description: Oxygen therapy through high flow nasal cannula (HFNC). Continuous monitoring of vital signs. Inspired fraction of oxygen will be titrated to maintain a capillary saturation of ≥92%. Prone positioning will be allowed as a rescue therapy.
arm group label: Awake prone positioning
arm group type: Experimental
description: Oxygen therapy through high flow nasal cannula (HFNC). Patients will be asked to remain in prone position throughout the day as long as possible, with breaks according to tolerance. Pillows will be offered for maximizing comfort at chest, pelvis and knees. Monitoring of vital signs will not be suspended. Inspired fraction of oxygen will be titrated to maintain a capillary saturation of ≥92%.
intervention type: Procedure
intervention name: Awake prone positioning
description: Patients will be asked to remain in prone position or lateral decubitus throughout the day as long as possible.
arm group label: Awake prone positioning
intervention type: Procedure
intervention name: Standard oxygen therapy
description: Oxygen therapy through high flow nasal cannula (HFNC). Inspired fraction of oxygen will be titrated to maintain a capillary saturation of ≥92%
arm group label: Standard oxygen therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Miguel Ibarra-Estrada
role: Principal Investigator
affiliation: Investigator
facility: 
facility: 
country: Mexico
responsible party type: Principal Investigator
investigator affiliation: Hospital Civil de Guadalajara
investigator full name: Miguel Á Ibarra-Estrada
investigator title: Principal investigator
mesh term: COVID-19
sharing ipd: No