<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/NCT04477954</url>
  </required_header>
  <id_info>
    <org_study_id>AAMHEI2020-1</org_study_id>
    <nct_id>NCT04477954</nct_id>
  </id_info>
  <brief_title>Hyperbaric Oxygen as an Adjuvant Treatment for Patients With Covid-19 Severe Hypoxemia</brief_title>
  <official_title>Hyperbaric Oxygen as an Adjuvant Treatment for Patients With Covid-19 Severe Hypoxemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Asociación Argentina de Medicina Hiperbárica e Investigación</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hospital de Infecciosas Francisco Javier Muniz</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital General de Agudos D. F. Santojanni</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Central de San Isidro Dr. Melchor Angel Posse</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Asociación Argentina de Medicina Hiperbárica e Investigación</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The severity of COVID-19 is related to the level of hypoxemia, respiratory failure, how long&#xD;
      it lasts and how refractory it is at increasing concentrations of inspired oxygen. The&#xD;
      inability to perform hematosis due to edema that occurs from acute inflammation could be&#xD;
      attenuated by the administration of hyperbaric oxygen (HBO). Recently, it has been reported&#xD;
      benefits in this matter in patients with SARS-CoV-2 hypoxemic pneumonia in China; where the&#xD;
      administration of repeated HBO sessions decreased the need for mechanical ventilation (MV) in&#xD;
      patients admitted to the Intensive Care Unit due to COVID-19. Hyperbaric oxygen is capable of&#xD;
      increasing drastically the amount of dissolved oxygen in the blood and maintain an adequate&#xD;
      supply oxygen to the tissues. In addition to this, it can influence immune processes, both&#xD;
      humoral and cellular, allowing to reduce the intensity of the response inflammatory and&#xD;
      stimulate antioxidant defenses. HBO is considered safe and it has very few adverse events, it&#xD;
      is a procedure approved by our authorities regulatory for several years. In the current&#xD;
      context of the pandemic by COVID-19 and worldwide reports of mortality associated with severe&#xD;
      cases of respiratory failure, it is essential to propose therapeutical strategies to limit or&#xD;
      decrease respiratory compromise of severe stages by COVID-19. That is why, it is proposed to&#xD;
      carry out this research to assess whether HBO treatment can improve the evolution of patients&#xD;
      with COVID-19 severe hypoxemia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Investigators and Ethic Committee endorsed early suspension of the protocol because of&#xD;
    superiority and safety. For the interim analysys, the statistical methodology presented by&#xD;
    Pocock was followed.&#xD;
  </why_stopped>
  <start_date type="Actual">July 6, 2020</start_date>
  <completion_date type="Actual">December 30, 2020</completion_date>
  <primary_completion_date type="Actual">November 6, 2020</primary_completion_date>
  <phase>Phase 2</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>Parallel Assignment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to normalize the oxygen requirement (oxygen dependence)</measure>
    <time_frame>15-30 days.</time_frame>
    <description>Time to normalize the oxygen requirement: Allowing a pulse oximetry value in ambient air greater than or equal 93% and/or arterial blood gas with PaO2 value greater than 60 mmHg in ambient air.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Need for Invasive Mechanical Ventilation (IMV) and / or Respiratory Distress Syndrome Acute (ARDS)</measure>
    <time_frame>30 days</time_frame>
    <description>Number of patients who required IMV after being enrolled</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Development of Acute Respiratory Distress Syndrome (ARDS)</measure>
    <time_frame>30 days</time_frame>
    <description>Number of patients who required IMV and / or had a diagnosis of ARDS after being enrolled.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>30-day mortality</measure>
    <time_frame>30 days</time_frame>
    <description>Number of patients who died in that period since enrollment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hypotension with vasopressor requirement</measure>
    <time_frame>30 days</time_frame>
    <description>Number of patients with hypotension who were administered vasopressors in this period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>45 days / 60 days / 90 days and 180 days</time_frame>
    <description>Number of patients who died in that period since enrollment.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Adverse events</measure>
    <time_frame>4 hours finished session</time_frame>
    <description>Number of adverse events reported related to the device (Revitalair 430 hyperbaric chamber): otalgias, ear obstruction, barotrauma, significant and constant changes in blood pressure, heart rate and others</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>Experimental HBOT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment (device). Patients will receive 90 minutes of hyperbaric oxygen at 1,45 ATA in a Revitalair430 hyperbaric chamber, and then they will continue with standard care and normobaric oxygen.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Hyperbaric Oxygen</intervention_name>
    <description>Hyperbaric oxygen therapy (HBOT): inhalation of pressurized oxygen through a hyperbaric chamber (Revitalair430)</description>
    <arm_group_label>Experimental HBOT</arm_group_label>
    <other_name>HBOT</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 years, all sexes.&#xD;
&#xD;
          -  No previous hospitalizations in the last 6 months.&#xD;
&#xD;
          -  Positive diagnostic test for COVID-19 according to the guidelines of the Argetine&#xD;
             Ministry of Health at the time of enrollment.&#xD;
&#xD;
          -  Patient in Intensive Care Unit with oxygen need: Need for continuous supply of oxygen&#xD;
             to maintain saturation by oximetry pulse (SpO2) greater than or equal to 93% or&#xD;
             arterial gas with PaO2 value greater than 60 mmHg&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  18 years of age.&#xD;
&#xD;
          -  Person unable to give consent.&#xD;
&#xD;
          -  Person who refuses to participate.&#xD;
&#xD;
          -  Pregnancy and lactation&#xD;
&#xD;
          -  Participating in other study&#xD;
&#xD;
          -  Requirement for mechanical ventilation.&#xD;
&#xD;
          -  Inability to maintain prolonged sitting position (at least 2 hours)&#xD;
&#xD;
          -  Subject with contraindications to HBOT (pulmonary shock, bullae, emphysema or&#xD;
             untreated pneumothorax, severe seizures, uncontrolled hypertension, chronic&#xD;
             obstructive disease of grade III or IV).&#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>Mariana Cannellotto, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Asociación Argentina de Medicina Hiperbárica e Investigación</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mariano Duarte, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Asociación Argentina de Medicina Hiperbárica e Investigación</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Liliana Jorda-Vargas</last_name>
    <role>Principal Investigator</role>
    <affiliation>Asociación Argentina de Medicina Hiperbárica e Investigación</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Fabrizio Verdini, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Asociación Argentina de Medicina Hiperbárica e Investigación</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Central de San Isidro Dr. Angel Melchor Posse</name>
      <address>
        <city>San Isidro</city>
        <state>Buenos Aires</state>
        <zip>1641</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Infecciosas F. J. Muñiz</name>
      <address>
        <city>Ciudad Autonoma de Buenos AIres</city>
        <state>Caba</state>
        <zip>1282</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General de Agudos D.F Santojanni</name>
      <address>
        <city>Ciudad Autonoma de Buenos AIres</city>
        <state>Caba</state>
        <zip>1408</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>July 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>January 13, 2021</last_update_submitted>
  <last_update_submitted_qc>January 13, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Asociación Argentina de Medicina Hiperbárica e Investigación</investigator_affiliation>
    <investigator_full_name>Mariana Cannellotto</investigator_full_name>
    <investigator_title>President</investigator_title>
  </responsible_party>
  <keyword>Hyperbaric Oxygen</keyword>
  <keyword>Covid-19</keyword>
  <keyword>Hypoxemia</keyword>
  <keyword>Sars-CoV2</keyword>
  <keyword>Hyperbaric Chamber</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Hypoxia</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/NCT04477954
org study id: AAMHEI2020-1
nct id: NCT04477954
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The severity of COVID-19 is related to the level of hypoxemia, respiratory failure, how long
      it lasts and how refractory it is at increasing concentrations of inspired oxygen. The
      inability to perform hematosis due to edema that occurs from acute inflammation could be
      attenuated by the administration of hyperbaric oxygen (HBO). Recently, it has been reported
      benefits in this matter in patients with SARS-CoV-2 hypoxemic pneumonia in China; where the
      administration of repeated HBO sessions decreased the need for mechanical ventilation (MV) in
      patients admitted to the Intensive Care Unit due to COVID-19. Hyperbaric oxygen is capable of
      increasing drastically the amount of dissolved oxygen in the blood and maintain an adequate
      supply oxygen to the tissues. In addition to this, it can influence immune processes, both
      humoral and cellular, allowing to reduce the intensity of the response inflammatory and
      stimulate antioxidant defenses. HBO is considered safe and it has very few adverse events, it
      is a procedure approved by our authorities regulatory for several years. In the current
      context of the pandemic by COVID-19 and worldwide reports of mortality associated with severe
      cases of respiratory failure, it is essential to propose therapeutical strategies to limit or
      decrease respiratory compromise of severe stages by COVID-19. That is why, it is proposed to
      carry out this research to assess whether HBO treatment can improve the evolution of patients
      with COVID-19 severe hypoxemia.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Time to normalize the oxygen requirement (oxygen dependence)
time frame: 15-30 days.
description: Time to normalize the oxygen requirement: Allowing a pulse oximetry value in ambient air greater than or equal 93% and/or arterial blood gas with PaO2 value greater than 60 mmHg in ambient air.
measure: Need for Invasive Mechanical Ventilation (IMV) and / or Respiratory Distress Syndrome Acute (ARDS)
time frame: 30 days
description: Number of patients who required IMV after being enrolled
measure: Development of Acute Respiratory Distress Syndrome (ARDS)
time frame: 30 days
description: Number of patients who required IMV and / or had a diagnosis of ARDS after being enrolled.
measure: 30-day mortality
time frame: 30 days
description: Number of patients who died in that period since enrollment
measure: Hypotension with vasopressor requirement
time frame: 30 days
description: Number of patients with hypotension who were administered vasopressors in this period
measure: Mortality
time frame: 45 days / 60 days / 90 days and 180 days
description: Number of patients who died in that period since enrollment.
measure: Adverse events
time frame: 4 hours finished session
description: Number of adverse events reported related to the device (Revitalair 430 hyperbaric chamber): otalgias, ear obstruction, barotrauma, significant and constant changes in blood pressure, heart rate and others
arm group label: Experimental HBOT
arm group type: Experimental
description: Treatment (device). Patients will receive 90 minutes of hyperbaric oxygen at 1,45 ATA in a Revitalair430 hyperbaric chamber, and then they will continue with standard care and normobaric oxygen.
arm group label: Standard care
arm group type: No Intervention
intervention type: Combination Product
intervention name: Hyperbaric Oxygen
description: Hyperbaric oxygen therapy (HBOT): inhalation of pressurized oxygen through a hyperbaric chamber (Revitalair430)
arm group label: Experimental HBOT
other name: HBOT
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mariana Cannellotto, MD
role: Study Chair
affiliation: Asociación Argentina de Medicina Hiperbárica e Investigación
last name: Mariano Duarte, PhD
role: Principal Investigator
affiliation: Asociación Argentina de Medicina Hiperbárica e Investigación
last name: Liliana Jorda-Vargas
role: Principal Investigator
affiliation: Asociación Argentina de Medicina Hiperbárica e Investigación
last name: Fabrizio Verdini, MD
role: Principal Investigator
affiliation: Asociación Argentina de Medicina Hiperbárica e Investigación
facility: 
facility: 
facility: 
country: Argentina
responsible party type: Principal Investigator
investigator affiliation: Asociación Argentina de Medicina Hiperbárica e Investigación
investigator full name: Mariana Cannellotto
investigator title: President
mesh term: COVID-19
mesh term: Hypoxia
sharing ipd: No