<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/NCT04497454</url>
  </required_header>
  <id_info>
    <org_study_id>CAAE: 30938720800000068</org_study_id>
    <nct_id>NCT04497454</nct_id>
  </id_info>
  <brief_title>Mechanical Ventilation Strategy for Coronavirus Disease 2019 (COVID-19)</brief_title>
  <acronym>COVEN</acronym>
  <official_title>Mechanical Ventilation Strategy for Coronavirus Disease 2019 (COVID-19) - COVEN Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>InCor Heart Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Sao Paulo General Hospital</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective, randomized, single-center, open-label controlled trial, designed to&#xD;
      compare the efficacy of two ventilation strategies (Low Tidal Volume and positive&#xD;
      end-expiratory pressure (PEEP) based on the Acute Respiratory Distress Syndrome (ARDS)&#xD;
      Network low PEEP-fraction of inspired oxygen inspired oxygen fraction (FIO2) Table versus Low&#xD;
      Driving Pressure and PEEP guided by Electrical Impedance Tomography (EIT) in reducing daily&#xD;
      lung injury score in patients with acute respiratory distress syndrome caused by COVID-19.&#xD;
      The two strategies incorporate different prioritizations of clinical variables. The PEEP-FIO2&#xD;
      table strategy aims to reduce lung overdistension, even if it requires tolerating worse gas&#xD;
      exchange. EIT-guided strategy prioritizes mechanical stress protection, avoiding alveolar&#xD;
      overdistension and collapse.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Mechanical ventilatory strategy of the ARDS Network low PEEP-FiO2 table will be followed in&#xD;
      the control arm. This strategy consists of at least 12 hours of controlled mechanical&#xD;
      ventilation following prespecified PEEP and FiO2 combinations chosen dynamically targeting&#xD;
      oxygenation. Tidal volume is set at 4-6 mL/Kg of predicted body weight (PBW) and plateau&#xD;
      pressure is kept below 30 centimeters of water (cmH2O). Respiratory rate can be as high as 35&#xD;
      breaths per minute titrated to a potential of hydrogen (pH) 7.30-7.45. As oxygenation&#xD;
      improves, patients are transitioned to assisted ventilation and then to pressure support&#xD;
      ventilation until they are ready to be liberated from the ventilator. During this phase, no&#xD;
      attempt is made to control plateau pressures or tidal volumes. In the intervention arm,&#xD;
      minimizing tidal lung strain by keeping driving pressure below 16 cmH2O throughout the&#xD;
      mechanical ventilation period will be targeted. The controlled phase will last at least 48&#xD;
      hours. PEEP will be selected according to a PEEP titration maneuver with EIT at the start of&#xD;
      the intervention. This PEEP level will be kept until extubation. Respiratory rate can be as&#xD;
      high as 50 breaths per minute targeting a pH of 7.15-7.45.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 8, 2020</start_date>
  <completion_date type="Anticipated">December 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">July 1, 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>Prospective, randomized, single-center, open-label, superiority, controlled trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Average daily Modified Lung injury score until day 28</measure>
    <time_frame>daily</time_frame>
    <description>This score originally ranges from 0 to 4 points based on the average of 4 parameters (PaO2/FiO2, chest X-Ray, PEEP level, and Respiratory compliance). In the modified version, if the patient dies, he or she automatically receives a score of 5 irrespective of the other four parameters. If the patient is extubated, the score is automatically zero. We also substituted FiO2 for PEEP guaranteeing equivalence of the score when either the low or high PEEP-FiO2 table is applied.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>High oxygen dependence free days until day 28</measure>
    <time_frame>28 days</time_frame>
    <description>Number of days with less than or equal to 1 Liter/min of oxygen supplementation until day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mechanical ventilation free days until day 28</measure>
    <time_frame>28 days</time_frame>
    <description>Number of days free of mechanical ventilation assistance after protocol inclusion and before day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of shock or barotrauma</measure>
    <time_frame>28 days</time_frame>
    <description>Occurrence of shock (persistent hypotension despite rescue measures) and incidence of barotrauma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of acute renal failure requiring renal replacement therapy</measure>
    <time_frame>28 days</time_frame>
    <description>Occurrence of acute renal failure that justifies renal replacement therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>28-day mortality</measure>
    <time_frame>28 days</time_frame>
    <description>Percentage of patients who died in each arm up to 28 days</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">128</enrollment>
  <condition>Respiratory Distress Syndrome</condition>
  <condition>Mechanical Ventilation</condition>
  <condition>SARS (Severe Acute Respiratory Syndrome)</condition>
  <arm_group>
    <arm_group_label>ARDSNet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>ARDSNet protocol (low PEEP-FiO2 table). Ventilatory mode: volume-controlled ventilation Tidal volume (VT) will be adjusted to 4-6 mL/Kg of PBW and Plateau pressure &lt; 30 cmH2O for the at least the first 12 hours after inclusion in the protocol pH should be maintained between 7.35-7.45 Oxygenation (SpO2) target ranges 90-95% Maximum respiratory rate = 35 breaths/min PEEP and FIO2 adjusted according to the low PEEP-FiO2 Table.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EIT-Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The goal is to maintain driving pressure (DP) &lt; 16 cmH2O. Ventilatory mode: pressure-controlled ventilation After a recruitment a maneuver, PEEP will be chosen according to a PEEP titration maneuver monitored with electrical impedance tomography Plateau pressure may exceed 30 cmH2O and VT may exceed 6 mL/Kg if DP &lt; 16 cmH2O pH should be maintained between 7.15-7.40 Oxygenation (SpO2) target ranges 90 -95% Maximum respiratory rate = 50 bpm</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>EIT-Group</intervention_name>
    <description>A mechanical ventilation strategy with the main goal to maintain DP &lt; 16 cmH2O</description>
    <arm_group_label>EIT-Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>ARDSNet</intervention_name>
    <description>Low PEEP-FiO2 table ARDS Network ventilation protocol</description>
    <arm_group_label>ARDSNet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients under mechanical ventilation with ARDS (Berlin definition) caused by SARS-COV2&#xD;
        infection:&#xD;
&#xD;
          -  ARDS diagnosis in less than 24 hours&#xD;
&#xD;
          -  Respiratory System Compliance of 0.6 mL/cmH2O/Kg of PBW&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 18 years&#xD;
&#xD;
          -  Active bronchopleural fistula&#xD;
&#xD;
          -  History of chronic and disabling respirator disease, requiring home oxygen treatment&#xD;
&#xD;
          -  Chronic pulmonary arterial hypertension (pulmonary artery systolic pressure &gt; 40 mmHg)&#xD;
&#xD;
          -  Huge intrathoracic tumoral mass&#xD;
&#xD;
          -  Electrical impedance tomography monitoring contraindications (as thoracic wounds or&#xD;
             burns, electronic implantable devices)&#xD;
&#xD;
          -  Hemodynamic instability (systolic pressure &lt; 80 mmHg or mean arterial pressure &lt; 60&#xD;
             mmHg, despite vasopressor drugs; and/or heart rate &lt; 55bpm) - this patient may be&#xD;
             included after recovered from hemodynamic instability&#xD;
&#xD;
          -  Not drained pneumothorax or subcutaneous emphysema or bronchopleural fistula&#xD;
&#xD;
          -  Patients at risk of intracranial hypertension development or post Cardiopulmonary&#xD;
             resuscitation (first 72 hours)&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Impossibility of monitoring with EIT&#xD;
&#xD;
          -  Not committed to full support or life expectation &lt; 24 hours&#xD;
&#xD;
          -  Legal responsible or clinical team refusal to participate in the study.&#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>Eduardo LV Costa, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital das Clinicas from University of São Paulo</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Eduardo LV Costa, PhD</last_name>
    <phone>+551130617361</phone>
    <email>eduardoleitecosta@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Maria AM Nakamura, PhD</last_name>
    <phone>+551130617151</phone>
    <email>mamiyukinakamura@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>USP Instituto do Coração</name>
      <address>
        <city>São Paulo</city>
        <zip>05.403-010</zip>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eduardo LV Costa</last_name>
      <phone>+551130667361</phone>
      <email>eduardoleitecosta@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Maria AM Nakamura</last_name>
      <phone>+551130667151</phone>
      <email>mamiyukinakamura@gmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>July 31, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>May 5, 2022</last_update_submitted>
  <last_update_submitted_qc>May 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Severe Acute Respiratory Syndrome</mesh_term>
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Syndrome</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/NCT04497454
org study id: CAAE: 30938720800000068
nct id: NCT04497454
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a prospective, randomized, single-center, open-label controlled trial, designed to
      compare the efficacy of two ventilation strategies (Low Tidal Volume and positive
      end-expiratory pressure (PEEP) based on the Acute Respiratory Distress Syndrome (ARDS)
      Network low PEEP-fraction of inspired oxygen inspired oxygen fraction (FIO2) Table versus Low
      Driving Pressure and PEEP guided by Electrical Impedance Tomography (EIT) in reducing daily
      lung injury score in patients with acute respiratory distress syndrome caused by COVID-19.
      The two strategies incorporate different prioritizations of clinical variables. The PEEP-FIO2
      table strategy aims to reduce lung overdistension, even if it requires tolerating worse gas
      exchange. EIT-guided strategy prioritizes mechanical stress protection, avoiding alveolar
      overdistension and collapse.
Mechanical ventilatory strategy of the ARDS Network low PEEP-FiO2 table will be followed in
      the control arm. This strategy consists of at least 12 hours of controlled mechanical
      ventilation following prespecified PEEP and FiO2 combinations chosen dynamically targeting
      oxygenation. Tidal volume is set at 4-6 mL/Kg of predicted body weight (PBW) and plateau
      pressure is kept below 30 centimeters of water (cmH2O). Respiratory rate can be as high as 35
      breaths per minute titrated to a potential of hydrogen (pH) 7.30-7.45. As oxygenation
      improves, patients are transitioned to assisted ventilation and then to pressure support
      ventilation until they are ready to be liberated from the ventilator. During this phase, no
      attempt is made to control plateau pressures or tidal volumes. In the intervention arm,
      minimizing tidal lung strain by keeping driving pressure below 16 cmH2O throughout the
      mechanical ventilation period will be targeted. The controlled phase will last at least 48
      hours. PEEP will be selected according to a PEEP titration maneuver with EIT at the start of
      the intervention. This PEEP level will be kept until extubation. Respiratory rate can be as
      high as 50 breaths per minute targeting a pH of 7.15-7.45.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Prospective, randomized, single-center, open-label, superiority, controlled trial
primary purpose: Treatment
masking: None (Open Label)
measure: Average daily Modified Lung injury score until day 28
time frame: daily
description: This score originally ranges from 0 to 4 points based on the average of 4 parameters (PaO2/FiO2, chest X-Ray, PEEP level, and Respiratory compliance). In the modified version, if the patient dies, he or she automatically receives a score of 5 irrespective of the other four parameters. If the patient is extubated, the score is automatically zero. We also substituted FiO2 for PEEP guaranteeing equivalence of the score when either the low or high PEEP-FiO2 table is applied.
measure: High oxygen dependence free days until day 28
time frame: 28 days
description: Number of days with less than or equal to 1 Liter/min of oxygen supplementation until day 28
measure: Mechanical ventilation free days until day 28
time frame: 28 days
description: Number of days free of mechanical ventilation assistance after protocol inclusion and before day 28
measure: Incidence of shock or barotrauma
time frame: 28 days
description: Occurrence of shock (persistent hypotension despite rescue measures) and incidence of barotrauma
measure: Incidence of acute renal failure requiring renal replacement therapy
time frame: 28 days
description: Occurrence of acute renal failure that justifies renal replacement therapy
measure: 28-day mortality
time frame: 28 days
description: Percentage of patients who died in each arm up to 28 days
arm group label: ARDSNet
arm group type: Active Comparator
description: ARDSNet protocol (low PEEP-FiO2 table). Ventilatory mode: volume-controlled ventilation Tidal volume (VT) will be adjusted to 4-6 mL/Kg of PBW and Plateau pressure < 30 cmH2O for the at least the first 12 hours after inclusion in the protocol pH should be maintained between 7.35-7.45 Oxygenation (SpO2) target ranges 90-95% Maximum respiratory rate = 35 breaths/min PEEP and FIO2 adjusted according to the low PEEP-FiO2 Table.
arm group label: EIT-Group
arm group type: Experimental
description: The goal is to maintain driving pressure (DP) < 16 cmH2O. Ventilatory mode: pressure-controlled ventilation After a recruitment a maneuver, PEEP will be chosen according to a PEEP titration maneuver monitored with electrical impedance tomography Plateau pressure may exceed 30 cmH2O and VT may exceed 6 mL/Kg if DP < 16 cmH2O pH should be maintained between 7.15-7.40 Oxygenation (SpO2) target ranges 90 -95% Maximum respiratory rate = 50 bpm
intervention type: Other
intervention name: EIT-Group
description: A mechanical ventilation strategy with the main goal to maintain DP < 16 cmH2O
arm group label: EIT-Group
intervention type: Other
intervention name: ARDSNet
description: Low PEEP-FiO2 table ARDS Network ventilation protocol
arm group label: ARDSNet
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Eduardo LV Costa, PhD
role: Principal Investigator
affiliation: Hospital das Clinicas from University of São Paulo
last name: Eduardo LV Costa, PhD
phone: +551130617361
email: eduardoleitecosta@gmail.com
last name: Maria AM Nakamura, PhD
phone: +551130617151
email: mamiyukinakamura@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Brazil
responsible party type: Sponsor
mesh term: Severe Acute Respiratory Syndrome
mesh term: COVID-19
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Syndrome
sharing ipd: No