<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/NCT04402879</url>
  </required_header>
  <id_info>
    <org_study_id>REB20-0518</org_study_id>
    <nct_id>NCT04402879</nct_id>
  </id_info>
  <brief_title>CORONA (COvid pRONe hypoxemiA): Prone Positioning for Hypoxemic COVID-19 Patients With Do-not-intubate Goals</brief_title>
  <acronym>CORONA</acronym>
  <official_title>A Prospective Randomized Trial of Prone Positioning Versus Usual Care for Patients With Do-not-intubate Goals of Care and Hypoxemic Respiratory Failure During the Coronavirus SARS-CoV-2 (COVID-19) Pandemic</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Calgary</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Alberta Health services</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Calgary</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>
      The purpose of this trial is to determine whether Prone Positioning (PP) improves outcomes&#xD;
      for non-intubated hospitalized patients with hypoxemic respiratory failure due to COVID-19,&#xD;
      who are not candidates for mechanical ventilation in the ICU. The investigators hypothesize&#xD;
      that PP will reduce in-hospital mortality or discharge to hospice, compared with usual care&#xD;
      for non-intubated patients with do-not-intubate goals of care with hypoxemic respiratory&#xD;
      failure due to probable COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      As part of the management of COVID-19 related severe ARDS, the World Health Organization&#xD;
      (WHO) recommends prone positioned mechanical ventilation. At this time, it is unclear whether&#xD;
      there is a role for prone positioning (PP) of non-mechanically ventilated patients.&#xD;
&#xD;
      The objective of this trial is to determine whether PP improves outcomes for non-intubated&#xD;
      hospitalized patients with hypoxemic respiratory failure due to COVID-19, who are not&#xD;
      candidates for mechanical ventilation in the ICU. The investigators hypothesize that PP will&#xD;
      reduce in-hospital mortality or discharge to hospice, compared with usual care for&#xD;
      non-intubated patients with do-not-intubate goals of care with hypoxemic respiratory failure&#xD;
      due to probable COVID-19.&#xD;
&#xD;
      Patients randomized to the intervention arm will continue with prone positioning until study&#xD;
      inclusion criteria are no longer met, discharge from hospital, day 60 in hospital, or until&#xD;
      death or discharge to hospice. Daily assessments will occur until day 60 or until the patient&#xD;
      is discharged from hospital or is deceased. The investigators anticipate recruitment to be&#xD;
      completed within 12 months of starting the trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 10, 2020</start_date>
  <completion_date type="Anticipated">June 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 1, 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>
    <intervention_model_description>This is a prospective, unblinded, randomized controlled trial at four (4) medical sites in Calgary, Alberta.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hospital mortality or discharge to hospice</measure>
    <time_frame>60 days</time_frame>
    <description>In-hospital mortality or discharge to hospice at Day 60.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse Events and Serious Adverse Events</measure>
    <time_frame>60 days</time_frame>
    <description>An Adverse Event (AE) is any unfavourable or other finding (including clinically significant laboratory tests), symptom or disease occurring during the during of the study, whether or not it is considered to be related to the medicinal (investigational) product, not explicitly classified elsewhere in this protocol, and whether or not it is expected. A Serious Adverse Event (AE) is any unfavourable medical finding (including clinically significant laboratory tests) at any dose that:&#xD;
Results in death (primary outcome)&#xD;
Is life threatening&#xD;
Results in persistent of significant disability or incapacity&#xD;
Requires in in-patient hospitalisation or prolongation of Hospitalisation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in SpO2</measure>
    <time_frame>60 days</time_frame>
    <description>Change in SpO2 during each PP session (SpO2 in prone position - SpO2 prior to prone positioning). Clinicians will be asked to record this change for the first proning session per shift (for 12 hour shifts this will result in 2 proning sessions being documented per 24 hour period, and for 8 hour shifts this will result in 3 proning sessions being documented per 24 hour period).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital free days</measure>
    <time_frame>60 days</time_frame>
    <description>Number of hospital free days in the 60 days after enrolment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Admission to ICU</measure>
    <time_frame>60 days</time_frame>
    <description>Admission to the Intensive Care Unit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intubation and mechanical ventilation</measure>
    <time_frame>60 days</time_frame>
    <description>Patient is intubated and requires mechanical ventilation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Initiation of non-invasive ventilation (NIV) or high-flow nasal oxygen (HFNO).</measure>
    <time_frame>60 days</time_frame>
    <description>Patient requires non-invasive ventilation (NIV) or high-flow nasal oxygen (HFNO).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxygen-free days</measure>
    <time_frame>60 days</time_frame>
    <description>The number of oxygen-free days at Day 60 (censored at discharge).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In-hospital death (time)</measure>
    <time_frame>60 days</time_frame>
    <description>Time from admission to all-cause in-hospital death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death at 90 days</measure>
    <time_frame>90 days</time_frame>
    <description>Death at 90 days.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">596</enrollment>
  <condition>Severe Acute Respiratory Syndrome Coronavirus 2</condition>
  <condition>COVID-19</condition>
  <condition>Acute Respiratory Distress Syndrome</condition>
  <condition>ARDS</condition>
  <condition>Hypoxemic Respiratory Failure</condition>
  <arm_group>
    <arm_group_label>Prone Positioning (PP)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The intervention for this study is PP. Patients at participating sites allocated to the intervention arm of the study will be prompted by ward nurses and respiratory therapists to assume and maintain a prone position for varying durations, four times per day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control - usual management</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The control group will consist of standard medical care with no instructions or prompts to change positioning to staff or patients.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Prone Positioning (PP)</intervention_name>
    <description>The intervention for this study is PP. Patients at participating sites allocated to the intervention arm of the study will be prompted by ward nurses and respiratory therapists to assume and maintain a prone position for varying durations, four times per day until the occurrence of a primary outcome event or hospital discharge.&#xD;
The target duration (dose) of PP is &gt; 8 hours per day for up to 60 days, or until oxygen requirements are &lt; 2 L per minute or &lt; 2 L per minute above baseline home oxygen requirements.</description>
    <arm_group_label>Prone Positioning (PP)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Hospitalized patients with probable COVID-19. Probable is defined as Influenza like&#xD;
             illness (ILI) symptoms OR confirmed COVID-19 exposure AND COVID-19 testing performed.&#xD;
             ILI is defined as any one of the following symptoms including: fever, new or worsening&#xD;
             cough, coryza, new or worsening dyspnea, or sore throat.&#xD;
&#xD;
          -  Goals of care are do-not-intubate (R3 or M1/M2 in Alberta).&#xD;
&#xD;
          -  Need for oxygen ≥2 L to maintain SpO2 ≥92%. If the patient is on long-term oxygen, the&#xD;
             O2 requirements must be ≥2 L above their baseline.&#xD;
&#xD;
          -  Patient can be positioned to and from prone to supine with minimal assistance (maximum&#xD;
             one person assistance).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Decreased level of consciousness (Glasgow Coma Scale &lt; 10) or precluding ability to&#xD;
             self-reposition.&#xD;
&#xD;
          -  Hemodynamic instability (Systolic Blood Pressure &lt; 90 mmHg and or Lactate &gt;5 mmol/L or&#xD;
             HR &gt;120, not responsive to fluid resuscitation).&#xD;
&#xD;
          -  Complete bowel obstruction.&#xD;
&#xD;
          -  Active upper gastrointestinal bleeding.&#xD;
&#xD;
          -  Poor neck mobility or patient inability to lie prone comfortably.&#xD;
&#xD;
          -  Unstable spine, femur, or pelvic fractures.&#xD;
&#xD;
          -  Pregnancy - third trimester.&#xD;
&#xD;
          -  Full resuscitation status including ICU and willingness to accept invasive mechanical&#xD;
             ventilation (i.e. R1/R2 goals of care).&#xD;
&#xD;
          -  Imminent palliation or end of life expected on admission (i.e. C1/C2 goals of care).&#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>Ken Parhar, MD, MSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Calgary</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jason Weatherald, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Calgary</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ken Parhar, MD, MSc</last_name>
    <phone>403-944-0735</phone>
    <email>ken.parhar@ahs.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jason Weatherald, MD</last_name>
    <phone>403-943-4779</phone>
    <email>jcweathe@ucalgary.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Peter Lougheed Centre (PLC)</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T1Y 6J4</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jason Weatherald, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Foothills Hospital Intensive Care Unit</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 2T9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ken Parhar, MD, MSc</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Rockyview General Hospital</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2V 1P9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Kevin Solverson, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>South Health Campus</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T3M 1M4</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Henry T Stelfox, MD PhD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>December 14, 2020</last_update_submitted>
  <last_update_submitted_qc>December 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Calgary</investigator_affiliation>
    <investigator_full_name>Ken Kuljit Parhar, MD</investigator_full_name>
    <investigator_title>Consultant Intensivist &amp; Clinical Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Prone positioning</keyword>
  <keyword>non-intubated</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
    <mesh_term>Severe Acute Respiratory Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Respiratory Insufficiency</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Syndrome</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/NCT04402879
org study id: REB20-0518
nct id: NCT04402879
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this trial is to determine whether Prone Positioning (PP) improves outcomes
      for non-intubated hospitalized patients with hypoxemic respiratory failure due to COVID-19,
      who are not candidates for mechanical ventilation in the ICU. The investigators hypothesize
      that PP will reduce in-hospital mortality or discharge to hospice, compared with usual care
      for non-intubated patients with do-not-intubate goals of care with hypoxemic respiratory
      failure due to probable COVID-19.
As part of the management of COVID-19 related severe ARDS, the World Health Organization
      (WHO) recommends prone positioned mechanical ventilation. At this time, it is unclear whether
      there is a role for prone positioning (PP) of non-mechanically ventilated patients.

      The objective of this trial is to determine whether PP improves outcomes for non-intubated
      hospitalized patients with hypoxemic respiratory failure due to COVID-19, who are not
      candidates for mechanical ventilation in the ICU. The investigators hypothesize that PP will
      reduce in-hospital mortality or discharge to hospice, compared with usual care for
      non-intubated patients with do-not-intubate goals of care with hypoxemic respiratory failure
      due to probable COVID-19.

      Patients randomized to the intervention arm will continue with prone positioning until study
      inclusion criteria are no longer met, discharge from hospital, day 60 in hospital, or until
      death or discharge to hospice. Daily assessments will occur until day 60 or until the patient
      is discharged from hospital or is deceased. The investigators anticipate recruitment to be
      completed within 12 months of starting the trial.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a prospective, unblinded, randomized controlled trial at four (4) medical sites in Calgary, Alberta.
primary purpose: Treatment
masking: None (Open Label)
measure: Hospital mortality or discharge to hospice
time frame: 60 days
description: In-hospital mortality or discharge to hospice at Day 60.
measure: Adverse Events and Serious Adverse Events
time frame: 60 days
description: An Adverse Event (AE) is any unfavourable or other finding (including clinically significant laboratory tests), symptom or disease occurring during the during of the study, whether or not it is considered to be related to the medicinal (investigational) product, not explicitly classified elsewhere in this protocol, and whether or not it is expected. A Serious Adverse Event (AE) is any unfavourable medical finding (including clinically significant laboratory tests) at any dose that:
Results in death (primary outcome)
Is life threatening
Results in persistent of significant disability or incapacity
Requires in in-patient hospitalisation or prolongation of Hospitalisation
measure: Change in SpO2
time frame: 60 days
description: Change in SpO2 during each PP session (SpO2 in prone position - SpO2 prior to prone positioning). Clinicians will be asked to record this change for the first proning session per shift (for 12 hour shifts this will result in 2 proning sessions being documented per 24 hour period, and for 8 hour shifts this will result in 3 proning sessions being documented per 24 hour period).
measure: Hospital free days
time frame: 60 days
description: Number of hospital free days in the 60 days after enrolment.
measure: Admission to ICU
time frame: 60 days
description: Admission to the Intensive Care Unit.
measure: Intubation and mechanical ventilation
time frame: 60 days
description: Patient is intubated and requires mechanical ventilation.
measure: Initiation of non-invasive ventilation (NIV) or high-flow nasal oxygen (HFNO).
time frame: 60 days
description: Patient requires non-invasive ventilation (NIV) or high-flow nasal oxygen (HFNO).
measure: Oxygen-free days
time frame: 60 days
description: The number of oxygen-free days at Day 60 (censored at discharge).
measure: In-hospital death (time)
time frame: 60 days
description: Time from admission to all-cause in-hospital death.
measure: Death at 90 days
time frame: 90 days
description: Death at 90 days.
arm group label: Prone Positioning (PP)
arm group type: Experimental
description: The intervention for this study is PP. Patients at participating sites allocated to the intervention arm of the study will be prompted by ward nurses and respiratory therapists to assume and maintain a prone position for varying durations, four times per day.
arm group label: Control - usual management
arm group type: No Intervention
description: The control group will consist of standard medical care with no instructions or prompts to change positioning to staff or patients.
intervention type: Procedure
intervention name: Prone Positioning (PP)
description: The intervention for this study is PP. Patients at participating sites allocated to the intervention arm of the study will be prompted by ward nurses and respiratory therapists to assume and maintain a prone position for varying durations, four times per day until the occurrence of a primary outcome event or hospital discharge.
The target duration (dose) of PP is > 8 hours per day for up to 60 days, or until oxygen requirements are < 2 L per minute or < 2 L per minute above baseline home oxygen requirements.
arm group label: Prone Positioning (PP)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ken Parhar, MD, MSc
role: Principal Investigator
affiliation: University of Calgary
last name: Jason Weatherald, MD
role: Principal Investigator
affiliation: University of Calgary
last name: Ken Parhar, MD, MSc
phone: 403-944-0735
email: ken.parhar@ahs.ca
last name: Jason Weatherald, MD
phone: 403-943-4779
email: jcweathe@ucalgary.ca
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University of Calgary
investigator full name: Ken Kuljit Parhar, MD
investigator title: Consultant Intensivist & Clinical Assistant Professor
mesh term: COVID-19
mesh term: Coronavirus Infections
mesh term: Severe Acute Respiratory Syndrome
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Respiratory Insufficiency
mesh term: Acute Lung Injury
mesh term: Syndrome