<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/NCT04500626</url>
  </required_header>
  <id_info>
    <org_study_id>OHRI-HBOT-001</org_study_id>
    <nct_id>NCT04500626</nct_id>
  </id_info>
  <brief_title>Hyperbaric Versus Normobaric Oxygen Therapy for COVID-19 Patients</brief_title>
  <official_title>Multicentre Randomized Controlled Trial of Hyperbaric Versus Normobaric Oxygen Therapy for COVID-19 Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ottawa Hospital Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Climate Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ottawa Hospital Research Institute</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>
      At least 1 in 6 COVID-19 patients admitted to hospital to receive extra oxygen will die of&#xD;
      complications. In patients with COVID-19, invasive treatment such as mechanical ventilation&#xD;
      (e.g. breathing with a machine) is associated with a 50% increased risk of death. Invasive&#xD;
      treatments use a lot of healthcare resources in intensive care units and may lead to further&#xD;
      deaths if patients do not have access to care.&#xD;
&#xD;
      The investigators aim to improve outcomes for COVID-19 patients by implementing hyperbaric&#xD;
      oxygen therapy (HBOT). HBOT allows patients to breathe 100% oxygen in a special chamber at a&#xD;
      pressure higher than sea level. It is approved by Health Canada for 14 conditions. HBOT is&#xD;
      safe when administered by experienced teams.&#xD;
&#xD;
      There are two main causes of death in severe COVID-19 respiratory infections: (i) a decreased&#xD;
      diffusion of oxygen from the lungs to the blood and (ii) an increased inflammatory response&#xD;
      (also called a &quot;cytokine storm&quot;). HBOT leads to increased oxygen level in blood, has strong&#xD;
      anti-inflammatory effects, and may destroy the virus responsible for COVID-19 disease. The&#xD;
      initial experience with HBOT and COVID-19 from China, France and the United States is&#xD;
      promising in that it prevents further worsening of the condition and need for intensive care.&#xD;
&#xD;
      The investigators propose to test the effectiveness of HBOT for COVID-19 patients who are&#xD;
      admitted to hospital to receive extra oxygen. Using the most rigorous and innovative research&#xD;
      methods, this Canadian-led international study will operate at 5 centers across 3 countries&#xD;
      (Canada: Ottawa, Toronto, Edmonton; Switzerland: Geneva; UK: Rugby/London). The investigators&#xD;
      anticipate that when treated by HBOT, COVID-19 patients needing extra oxygen to breathe will&#xD;
      see significant health improvements as well as a decrease in complications, inflammation in&#xD;
      the blood, need for invasive care, death, and cost of care.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 15, 2021</start_date>
  <completion_date type="Anticipated">August 2022</completion_date>
  <primary_completion_date type="Anticipated">August 2022</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>7-level COVID Ordinal Outcome Scale</measure>
    <time_frame>Measured on Day 7</time_frame>
    <description>7-level scale based on patient's current status and need for oxygenation, also ability to resume normal activities (at higher levels). Range is 1-7. Higher number indicates better clinical outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>Duration of study (to Day 28)</time_frame>
    <description>Measured in days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days with oxygen supplementation</measure>
    <time_frame>Duration of study (to Day 28)</time_frame>
    <description>Number of days with oxygen supplementation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Daily oxygen flow values required to obtain saturation values ≥90%,</measure>
    <time_frame>Duration of study (to Day 28)</time_frame>
    <description>Measured in L/min</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU admission</measure>
    <time_frame>Duration of study (to Day 28)</time_frame>
    <description>Yes/No</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU length of stay</measure>
    <time_frame>Duration of study (to Day 28)</time_frame>
    <description>Measured in days, if applicable</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days on invasive mechanical ventilation or high flow oxygenation</measure>
    <time_frame>Duration of study (to Day 28)</time_frame>
    <description>Number of days on ventilator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major arterial and venous thrombotic events</measure>
    <time_frame>Duration of study (to Day 28)</time_frame>
    <description>e.g. stroke, pulmonary embolism, deep vein thrombosis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sleep quality</measure>
    <time_frame>Duration of study (to Day 28)</time_frame>
    <description>Sleep Quality Scale, measured from 0 to 10. Higher number indicates worse sleep quality: 0 = &quot;best possible sleep&quot;, 10 = &quot;worst possible sleep&quot;. Capelleri et. al; Health and Quality of Life Outcomes 2009: 7:54</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fatigue</measure>
    <time_frame>Duration of study (to Day 28)</time_frame>
    <description>Single-Item Fatigue Report Mark, measured from 1 to 10. Higher number indicates worse fatigue: 1 = &quot;not at all&quot;, 10 = &quot;extremely&quot;. van Hooff et al; J Occup Health 2007; 49:224-234.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>7-level COVID Ordinal Outcome Scale</measure>
    <time_frame>Measured on Day 28</time_frame>
    <description>Same scale as the primary outcome; different timing as a secondary outcome. Range is 1-7. Higher number indicates better clinical outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>Duration of study (to Day 28)</time_frame>
    <description>Number of deaths</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of any adverse events related to HBOT</measure>
    <time_frame>Duration of study (to Day 28)</time_frame>
    <description>Number of adverse events</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">234</enrollment>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>HBOT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>These patients will receive hyperbaric oxygen therapy (HBOT) in addition to usual treatment for COVID-19. HBOT sessions will be 75 minutes in length at a pressure of 2.0 ATA.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>These patients will receive usual treatment for COVID-19, including oxygenation at normal atmospheric pressure (normobaric oxygenation).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oxygen</intervention_name>
    <description>Hyperbaric oxygen therapy delivered in a monoplace or multi-place chamber. Supervised by a hyperbaric oxygen therapy physician and a chamber operator.</description>
    <arm_group_label>HBOT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or non-pregnant female patients&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Confirmed COVID-19 positive by RT-PCR or another validated method&#xD;
&#xD;
          -  Diagnosed with pneumonia requiring 21%&lt;FIO2≤100% to maintain saturation by pulse&#xD;
             oximetry (SpO2) ≥90%&#xD;
&#xD;
          -  Able and willing to comply with study procedures and follow-up examinations contained&#xD;
             within the written consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient clinical status felt to be incompatible with HBOT, e.g. respiratory failure&#xD;
             requiring mechanical ventilation&#xD;
&#xD;
          -  Pregnancy, determined by a serum or urine test&#xD;
&#xD;
          -  Hemodynamic instability requiring vasopressors&#xD;
&#xD;
          -  Inability to maintain a sitting position during treatment&#xD;
&#xD;
          -  Inability to effectively understand and communicate with the hyperbaric operator, or&#xD;
             to give consent&#xD;
&#xD;
          -  Inability to spontaneously equalize ears and refusal of myringotomies&#xD;
&#xD;
          -  Contraindications to HBOT (e.g. pneumothorax)&#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>Sylvain Boet, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Ottawa Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sylvain Boet, MD, PhD</last_name>
    <phone>613-737-8899</phone>
    <phone_ext>78187</phone_ext>
    <email>sboet@toh.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Joseph Burns, MSc</last_name>
    <phone>613-798-5555</phone>
    <phone_ext>14775</phone_ext>
    <email>josburns@ohri.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The Ottawa Hospital</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1Y4E9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Sylvain Boet, MD, PhD</last_name>
      <phone>6137985555</phone>
      <phone_ext>78187</phone_ext>
      <email>sboet@toh.on.ca</email>
    </contact>
    <contact_backup>
      <last_name>Joseph Burns, MSc</last_name>
      <phone>613-798-5555</phone>
      <phone_ext>14775</phone_ext>
      <email>josburns@ohri.ca</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Rouge Valley Hyperbaric Medical Centre</name>
      <address>
        <city>Scarborough</city>
        <state>Ontario</state>
        <zip>M1E 5E9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rita Katznelson, MD</last_name>
      <email>rita.katznelson@uhn.ca</email>
    </contact>
    <contact_backup>
      <last_name>Research Coordinator</last_name>
      <email>research@centenarypainclinic.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Rita Katznelson, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <link>
    <url>https://www.medrxiv.org/content/10.1101/2020.07.15.20154609v1</url>
    <description>Preprint of study protocol (brief version for publication)</description>
  </link>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>July 31, 2020</study_first_submitted>
  <study_first_submitted_qc>August 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>October 29, 2021</last_update_submitted>
  <last_update_submitted_qc>October 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hyperbaric oxygen therapy</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/NCT04500626
org study id: OHRI-HBOT-001
nct id: NCT04500626
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
At least 1 in 6 COVID-19 patients admitted to hospital to receive extra oxygen will die of
      complications. In patients with COVID-19, invasive treatment such as mechanical ventilation
      (e.g. breathing with a machine) is associated with a 50% increased risk of death. Invasive
      treatments use a lot of healthcare resources in intensive care units and may lead to further
      deaths if patients do not have access to care.

      The investigators aim to improve outcomes for COVID-19 patients by implementing hyperbaric
      oxygen therapy (HBOT). HBOT allows patients to breathe 100% oxygen in a special chamber at a
      pressure higher than sea level. It is approved by Health Canada for 14 conditions. HBOT is
      safe when administered by experienced teams.

      There are two main causes of death in severe COVID-19 respiratory infections: (i) a decreased
      diffusion of oxygen from the lungs to the blood and (ii) an increased inflammatory response
      (also called a "cytokine storm"). HBOT leads to increased oxygen level in blood, has strong
      anti-inflammatory effects, and may destroy the virus responsible for COVID-19 disease. The
      initial experience with HBOT and COVID-19 from China, France and the United States is
      promising in that it prevents further worsening of the condition and need for intensive care.

      The investigators propose to test the effectiveness of HBOT for COVID-19 patients who are
      admitted to hospital to receive extra oxygen. Using the most rigorous and innovative research
      methods, this Canadian-led international study will operate at 5 centers across 3 countries
      (Canada: Ottawa, Toronto, Edmonton; Switzerland: Geneva; UK: Rugby/London). The investigators
      anticipate that when treated by HBOT, COVID-19 patients needing extra oxygen to breathe will
      see significant health improvements as well as a decrease in complications, inflammation in
      the blood, need for invasive care, death, and cost of care.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: 7-level COVID Ordinal Outcome Scale
time frame: Measured on Day 7
description: 7-level scale based on patient's current status and need for oxygenation, also ability to resume normal activities (at higher levels). Range is 1-7. Higher number indicates better clinical outcome.
measure: Length of hospital stay
time frame: Duration of study (to Day 28)
description: Measured in days
measure: Days with oxygen supplementation
time frame: Duration of study (to Day 28)
description: Number of days with oxygen supplementation
measure: Daily oxygen flow values required to obtain saturation values ≥90%,
time frame: Duration of study (to Day 28)
description: Measured in L/min
measure: ICU admission
time frame: Duration of study (to Day 28)
description: Yes/No
measure: ICU length of stay
time frame: Duration of study (to Day 28)
description: Measured in days, if applicable
measure: Days on invasive mechanical ventilation or high flow oxygenation
time frame: Duration of study (to Day 28)
description: Number of days on ventilator
measure: Major arterial and venous thrombotic events
time frame: Duration of study (to Day 28)
description: e.g. stroke, pulmonary embolism, deep vein thrombosis
measure: Sleep quality
time frame: Duration of study (to Day 28)
description: Sleep Quality Scale, measured from 0 to 10. Higher number indicates worse sleep quality: 0 = "best possible sleep", 10 = "worst possible sleep". Capelleri et. al; Health and Quality of Life Outcomes 2009: 7:54
measure: Fatigue
time frame: Duration of study (to Day 28)
description: Single-Item Fatigue Report Mark, measured from 1 to 10. Higher number indicates worse fatigue: 1 = "not at all", 10 = "extremely". van Hooff et al; J Occup Health 2007; 49:224-234.
measure: 7-level COVID Ordinal Outcome Scale
time frame: Measured on Day 28
description: Same scale as the primary outcome; different timing as a secondary outcome. Range is 1-7. Higher number indicates better clinical outcome.
measure: Mortality
time frame: Duration of study (to Day 28)
description: Number of deaths
measure: Incidence of any adverse events related to HBOT
time frame: Duration of study (to Day 28)
description: Number of adverse events
arm group label: HBOT
arm group type: Experimental
description: These patients will receive hyperbaric oxygen therapy (HBOT) in addition to usual treatment for COVID-19. HBOT sessions will be 75 minutes in length at a pressure of 2.0 ATA.
arm group label: Control
arm group type: No Intervention
description: These patients will receive usual treatment for COVID-19, including oxygenation at normal atmospheric pressure (normobaric oxygenation).
intervention type: Drug
intervention name: Oxygen
description: Hyperbaric oxygen therapy delivered in a monoplace or multi-place chamber. Supervised by a hyperbaric oxygen therapy physician and a chamber operator.
arm group label: HBOT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sylvain Boet, MD, PhD
role: Principal Investigator
affiliation: The Ottawa Hospital
last name: Sylvain Boet, MD, PhD
phone: 613-737-8899
phone ext: 78187
email: sboet@toh.ca
last name: Joseph Burns, MSc
phone: 613-798-5555
phone ext: 14775
email: josburns@ohri.ca
facility: 
status: Not yet recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Canada
url: https://www.medrxiv.org/content/10.1101/2020.07.15.20154609v1
description: Preprint of study protocol (brief version for publication)
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: No