<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/NCT04415060</url>
  </required_header>
  <id_info>
    <org_study_id>2149</org_study_id>
    <nct_id>NCT04415060</nct_id>
  </id_info>
  <brief_title>SedAting With Volatile Anesthetics Critically Ill COVID-19 Patients in ICU: Effects On Ventilatory Parameters And Survival</brief_title>
  <acronym>SAVE-ICU</acronym>
  <official_title>SedAting With Volatile Anesthetics Critically Ill COVID-19 Patients in ICU: Effects On Ventilatory Parameters And Survival. Multicentre Open-label, Pragmatic, Randomized Controlled Trial and a Parallel Prospective (Non-randomized) Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sunnybrook Health Sciences Centre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sunnybrook Health Sciences Centre</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>
      Patients suffering lung failure, possibly from COVID-19 or hypoxic lung failure, will need&#xD;
      life-saving support from a breathing machine. Any patient needing this support requires drugs&#xD;
      to keep them sleepy, or &quot;sedated&quot; to be comfortable on this machine. Sedation is made&#xD;
      possible by using drugs given through a vein. Unfortunately, these drugs are in short supply&#xD;
      worldwide due to the high number of COVID-19 patients needing these machines.&#xD;
&#xD;
      Another way to provide sleep is by using gases that are breathed in. These are used every day&#xD;
      in operating rooms to perform surgery. These gases, also called &quot;inhaled agents&quot; can also be&#xD;
      used in intensive care units and may have several important benefits for patients and the&#xD;
      hospital. Research shows they may reduce swelling in the lung and increase oxygen levels,&#xD;
      which allows patients to recover faster and reduce the time spent on a breathing machine. In&#xD;
      turn, this allows the breathing machine to be used again for the next sick patient. These&#xD;
      drugs may also increase the number of patients who live through their illness. Inhaled agents&#xD;
      are widely available and their use could dramatically lesson the pressure on limited drug&#xD;
      supplies.&#xD;
&#xD;
      This research is a study being carried out in a number of hospitals that will compare how&#xD;
      well patients recover from these illnesses depending on which type of sedation drug they&#xD;
      receive. The plan is to evaluate the number who survive, their time spent on a breathing&#xD;
      machine and time in the hospital. This study may show immediate benefits and may provide a&#xD;
      cost effective and practical solution to the current challenges caring for patients and the&#xD;
      hospital space, equipment and drugs to the greatest benefit. Furthermore, the study will be&#xD;
      investigating inflammatory profile and neuro-cognitive profiles in ventilated patients.&#xD;
      Finally, this trial will be a team of experts in sedation drugs who care for patients with&#xD;
      proven or suspected COVID-19 who need lifesaving treatments.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Multicentre open-label, pragmatic, randomized controlled trial and a parallel prospective&#xD;
      (non-randomized) cohort study conducted in ICUs and ICU enabled environments caring in&#xD;
      critically ill COVID-19 and non-COVID hypoxic respiratory failure patients.&#xD;
&#xD;
      Participants will be mechanically ventilated and will be variably randomized, within 72 hours&#xD;
      of start of sedation treatment, in a 1:1 ratio to either an intravenous or inhaled&#xD;
      volatile-based sedation arm depending on availability of sedative drugs for both arms.&#xD;
      Stratification will be done by:&#xD;
&#xD;
        1. Age ≥ 65 years&#xD;
&#xD;
        2. participating centre&#xD;
&#xD;
        3. PaO2/FiO2 ratio of 150&#xD;
&#xD;
      Patients who cannot be randomized (due to technical or resource issues in some areas of the&#xD;
      hospital) will be entered into the parallel prospective (non-randomized) cohort study and&#xD;
      will receive intravenous or inhaled sedation as able in their designated unit.&#xD;
&#xD;
      Sedation will be administered according to standard sedation practice and in keeping with&#xD;
      current guidelines.&#xD;
&#xD;
      Participants will be followed:&#xD;
&#xD;
        -  daily in ICU until 30 days after enrollment, ICU discharge or death, whichever occurs&#xD;
           first;&#xD;
&#xD;
        -  at 30 days after last dose of drug administration by telephone or through the hospital&#xD;
           healthcare database;&#xD;
&#xD;
        -  at 60 days, 90 days, and 365 days after enrollment by telephone and/or through data&#xD;
           linkages with a provincial or hospital or state healthcare database;&#xD;
&#xD;
        -  Participants will have the option to participate in the neuro-cognitive and / or&#xD;
           biomarker assessments&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 15, 2020</start_date>
  <completion_date type="Anticipated">June 15, 2025</completion_date>
  <primary_completion_date type="Anticipated">June 15, 2024</primary_completion_date>
  <phase>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>
    <intervention_model_description>Multicentre open-label, pragmatic, randomized controlled trial and a parallel prospective (non-randomized) cohort study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hospital Mortality</measure>
    <time_frame>2 years</time_frame>
    <description>Does the use of inhaled volatile anesthetic-based sedation regimen improve participant hospital mortality as compared to standard intravenous sedation regimen with a 10% difference between groups for 752 participants.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ventilator-Free Days</measure>
    <time_frame>30 days</time_frame>
    <description>Does the use of inhaled volatile anesthetic-based sedation regimen improve participant ventilation outcomes after 30 days post enrollment, as compared to standard intravenous sedation regimen for 200 participants</description>
  </primary_outcome>
  <primary_outcome>
    <measure>ICU-Free Days</measure>
    <time_frame>30 days</time_frame>
    <description>Does the use of inhaled volatile anesthetic-based sedation regimen improve participant time spent in ICU, 30 days post enrollment, as compared to standard intravenous sedation regimen for 128 participants</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Participant Quality of Life at 3 and 12 months after discharge</measure>
    <time_frame>365 days</time_frame>
    <description>Does the use of inhaled volatile anesthetic-based sedation regimen improve participant quality of life outcomes at 3 and 12 months post discharge as compared to standard intravenous sedation regimen for 144 participants. The EQ-5D questionnaire will be completed at both time points</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median Daily Oxygenation</measure>
    <time_frame>3 days</time_frame>
    <description>To evaluate participant median daily oxygenation (PaO2/FiO2) at 3 days post enrollment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Delirium and Coma Free Days</measure>
    <time_frame>14 days</time_frame>
    <description>To evaluate the days alive and free from delirium and coma while in ICU for 14 days after enrollment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adjunctive ARDS therapies</measure>
    <time_frame>30 days</time_frame>
    <description>To evaluate participant need for adjunctive ARDS therapies (prone, nitric oxide, paralysis, ECMO) during ICU stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital-Free Days</measure>
    <time_frame>60 days</time_frame>
    <description>To evaluate the number of hospital-free days for participants, 60 days after enrollment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disability</measure>
    <time_frame>365 days</time_frame>
    <description>To evaluate participant disability at 3 and 12 months post discharge. The World Health Organization Disabiltity Assessment Score (WHODAS 2.0) will be completed at both timepoints. The scores assigned to each of the items - &quot;none&quot; (0), &quot;mild&quot; (1) &quot;moderate&quot; (2), &quot;severe&quot; (3) and &quot;extreme&quot; (4) - are summed. This method is referred to as simple scoring because the scores from each of the items are simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">758</enrollment>
  <condition>Covid19</condition>
  <condition>Hypoxic Respiratory Failure</condition>
  <arm_group>
    <arm_group_label>Inhaled - volatile anesthetic</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The ICU patient will be randomized to either Isoflurane or Sevoflurane, whichever is available at the hospital. Dosage will be modified as per health care team guidance for the best treatment of the participant.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The ICU patient will be randomized to standard of care, which is any IV sedation supplied by the hospital. Dosage will be modified as per health care team guidance for the best treatment of the participant.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-randomized</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>In this arm, ICU patients who cannot be randomized will receive inhaled or IV sedation as per available in their unit. This is done to try to obtain the maximum amount of information available from the patients present to our ICUs.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Isoflurane Inhalant Product</intervention_name>
    <description>Isoflurane will be administered using an inhalation device</description>
    <arm_group_label>Inhaled - volatile anesthetic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sevoflurane inhalant product</intervention_name>
    <description>Sevoflurane will be administered using an inhalation device</description>
    <arm_group_label>Inhaled - volatile anesthetic</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. ≥ 18 years of age&#xD;
&#xD;
          2. Mechanically ventilated and expected to remain mechanically ventilated at the end of&#xD;
             the next day&#xD;
&#xD;
          3. Receiving IV sedation by infusion or bolus for ≤72 hours to facilitate mechanical&#xD;
             ventilation Transferred patients with escalating ventilation needs are eligible for&#xD;
             recruitment within ≤72 hours of sedation commenced within the participating trial site&#xD;
             that they were transferred to.&#xD;
&#xD;
        Note: Intravenous sedation required to support mechanical ventilation includes use of one&#xD;
        or more of the following agents: benzodiazepines, propofol, ketamine, barbiturates, alpha-2&#xD;
        agonist, opioids. Patients receiving intravenous opioids only i.e., fentanyl ≥ 50mcg/hour,&#xD;
        hydromorphone ≥ 0.4mg/hour (or bolus q1h) for analgesia and sedation or agitation to assist&#xD;
        mechanical ventilation are eligible for inclusion.&#xD;
&#xD;
        4. a) Proven or suspected (under investigation) COVID-19, or b) COVID-19 negative patients&#xD;
        who have a PaO2FiO2 ratio ≤300 measured with arterial blood gas at least once during the 12&#xD;
        hours prior to enrollment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Contraindications to sedatives, such as propofol infusion syndrome or malignant&#xD;
             hyperthermia;&#xD;
&#xD;
          2. Known allergy to any of the ingredients or components of the investigational products;&#xD;
             sevoflurane or isoflurane;&#xD;
&#xD;
          3. Suspect or evidence of high intracranial pressure;&#xD;
&#xD;
          4. Severe brain injury that is likely to lead to sustained very low conscious levels or&#xD;
             vegetative state&#xD;
&#xD;
          5. Severe neuromuscular disorder for example amyotrophic lateral sclerosis, Gullian Barre&#xD;
             Syndrome that are the primary cause of needing ICU admission and mechanical&#xD;
             ventilation&#xD;
&#xD;
          6. One-lung ventilation or pneumonectomy;&#xD;
&#xD;
          7. Ideal estimated tidal volume too low for delivery of inhaled agents. Target (6ml/kg) &lt;&#xD;
             200ml;&#xD;
&#xD;
          8. Use of inhaled prostacyclin which is contraindicated in the presence of a miniature&#xD;
             vaporizer (i.e., Anesthesia Conserving Device). This agent has a high viscosity that&#xD;
             leads to poor vaporization of the volatile agent. Note: Other inhaled pulmonary&#xD;
             vasodilators such as nitric oxide can be safely administered in the presence of&#xD;
             miniature vaporizers. Use of prostacyclin is permissible with an anesthesia machine&#xD;
             and MADM;&#xD;
&#xD;
          9. Known pregnancy&#xD;
&#xD;
         10. Moribund patient not expected to survive &gt;12 hours&#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_contact>
    <last_name>Angela Jerath, MD</last_name>
    <phone>416.480.6100</phone>
    <email>angela.jerath@sunnybrook.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Iman Hussain</last_name>
    <email>SAVE-ICU@sunnybrook.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Alberta Hospital</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2B7</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nadia Baig</last_name>
      <phone>780-492-3817</phone>
      <email>Nadia.Baig@ahs.ca</email>
    </contact>
    <investigator>
      <last_name>Michael Jacka, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>London Health Sciences Centre - University Hospital</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 5A5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tracey Bentall</last_name>
      <phone>519-685-8500</phone>
      <phone_ext>32546</phone_ext>
      <email>TraceyC.Bentall@lhsc.on.ca</email>
    </contact>
    <investigator>
      <last_name>Marat Slessarev, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>London Health Sciences Centre - Victoria Hospital</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eileen Campbell</last_name>
      <phone>519-685-8500</phone>
      <phone_ext>55664</phone_ext>
      <email>Eileen.Campbell@lhsc.on.ca</email>
    </contact>
    <investigator>
      <last_name>Marat Slessarav, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Ottawa Hospital</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jessica Haines</last_name>
      <email>jhaines@toh.ca</email>
    </contact>
    <contact_backup>
      <last_name>Irene Watpool</last_name>
      <email>iwatpool@toh.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Johnathan Hooper, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sunnybrook Health Sciences Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lilia Kaustov</last_name>
      <phone>416.480.6100</phone>
      <email>Lilia.Kaustov@sunnybrook.ca</email>
    </contact>
    <investigator>
      <last_name>Angela Jerath, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Health Network - Toronto General Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2C4</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hesham Abdelhady</last_name>
      <phone>416-340-4800</phone>
      <phone_ext>6056</phone_ext>
      <email>Hesham.Abdelhady@uhn.ca</email>
    </contact>
    <contact_backup>
      <last_name>Tina Romagnuolo</last_name>
      <phone>416-340-4800</phone>
      <phone_ext>6056</phone_ext>
      <email>Tina.Romagnuolo@uhn.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Ewan Goligher, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Health Network - Toronto Western Hopsital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5T 2S8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Emad AlAzizi</last_name>
      <phone>416-603-5800</phone>
      <phone_ext>6237</phone_ext>
      <email>Emad.AlAzizi@uhnresearch.ca</email>
    </contact>
    <contact_backup>
      <last_name>Deborah Mancini</last_name>
      <phone>416-603-5800</phone>
      <phone_ext>6237</phone_ext>
      <email>Deborah.Mancini@uhnresearch.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Ian Randall, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de l'Université de Montréal</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H2X 3E4</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cindy Prie</last_name>
      <phone>514-890-8000</phone>
      <phone_ext>20065</phone_ext>
      <email>cindy.prie.chum@ssss.gouv.qc.ca</email>
    </contact>
    <investigator>
      <last_name>Francois-Martin Carrier, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>McGill University Health Centre - Royal Victoria Hospital</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Josie Campisi</last_name>
      <phone>514-934-1934</phone>
      <phone_ext>65542</phone_ext>
      <email>josie.campisi@muhc.mcgill.ca</email>
    </contact>
    <investigator>
      <last_name>Roupen Hatzakorzian, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Sacré-Coeur de Montréal</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H4J1C5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Virginie Williams</last_name>
      <phone>514-338-2222</phone>
      <phone_ext>3487</phone_ext>
      <email>virginie.williams.cnmtl@ssss.gouv.qc.ca</email>
    </contact>
    <investigator>
      <last_name>Alexandros Cavayas, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ)</name>
      <address>
        <city>Québec</city>
        <state>Quebec</state>
        <zip>G1V 4G5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Universite de Sherbrooke</name>
      <address>
        <city>Sherbrooke</city>
        <state>Quebec</state>
        <zip>J1K 2R1</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Elaine Carbonneau</last_name>
      <phone>819-346-1110</phone>
      <phone_ext>16208</phone_ext>
      <email>ecarbonneau.chus@ssss.gouv.qc.ca</email>
    </contact>
    <contact_backup>
      <last_name>Marie-Pier Bouchard</last_name>
      <phone>819-346-1110</phone>
      <phone_ext>16208</phone_ext>
      <email>marie-pier.bouchard.ciussse-chus@ssss.gouv.qc.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Frederick D'Aragon, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>April 25, 2023</last_update_submitted>
  <last_update_submitted_qc>April 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>sedation</keyword>
  <keyword>ICU</keyword>
  <keyword>volatile anesthetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Respiratory Insufficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sevoflurane</mesh_term>
    <mesh_term>Isoflurane</mesh_term>
  </intervention_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/NCT04415060
org study id: 2149
nct id: NCT04415060
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Patients suffering lung failure, possibly from COVID-19 or hypoxic lung failure, will need
      life-saving support from a breathing machine. Any patient needing this support requires drugs
      to keep them sleepy, or "sedated" to be comfortable on this machine. Sedation is made
      possible by using drugs given through a vein. Unfortunately, these drugs are in short supply
      worldwide due to the high number of COVID-19 patients needing these machines.

      Another way to provide sleep is by using gases that are breathed in. These are used every day
      in operating rooms to perform surgery. These gases, also called "inhaled agents" can also be
      used in intensive care units and may have several important benefits for patients and the
      hospital. Research shows they may reduce swelling in the lung and increase oxygen levels,
      which allows patients to recover faster and reduce the time spent on a breathing machine. In
      turn, this allows the breathing machine to be used again for the next sick patient. These
      drugs may also increase the number of patients who live through their illness. Inhaled agents
      are widely available and their use could dramatically lesson the pressure on limited drug
      supplies.

      This research is a study being carried out in a number of hospitals that will compare how
      well patients recover from these illnesses depending on which type of sedation drug they
      receive. The plan is to evaluate the number who survive, their time spent on a breathing
      machine and time in the hospital. This study may show immediate benefits and may provide a
      cost effective and practical solution to the current challenges caring for patients and the
      hospital space, equipment and drugs to the greatest benefit. Furthermore, the study will be
      investigating inflammatory profile and neuro-cognitive profiles in ventilated patients.
      Finally, this trial will be a team of experts in sedation drugs who care for patients with
      proven or suspected COVID-19 who need lifesaving treatments.
Multicentre open-label, pragmatic, randomized controlled trial and a parallel prospective
      (non-randomized) cohort study conducted in ICUs and ICU enabled environments caring in
      critically ill COVID-19 and non-COVID hypoxic respiratory failure patients.

      Participants will be mechanically ventilated and will be variably randomized, within 72 hours
      of start of sedation treatment, in a 1:1 ratio to either an intravenous or inhaled
      volatile-based sedation arm depending on availability of sedative drugs for both arms.
      Stratification will be done by:

        1. Age ≥ 65 years

        2. participating centre

        3. PaO2/FiO2 ratio of 150

      Patients who cannot be randomized (due to technical or resource issues in some areas of the
      hospital) will be entered into the parallel prospective (non-randomized) cohort study and
      will receive intravenous or inhaled sedation as able in their designated unit.

      Sedation will be administered according to standard sedation practice and in keeping with
      current guidelines.

      Participants will be followed:

        -  daily in ICU until 30 days after enrollment, ICU discharge or death, whichever occurs
           first;

        -  at 30 days after last dose of drug administration by telephone or through the hospital
           healthcare database;

        -  at 60 days, 90 days, and 365 days after enrollment by telephone and/or through data
           linkages with a provincial or hospital or state healthcare database;

        -  Participants will have the option to participate in the neuro-cognitive and / or
           biomarker assessments
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Multicentre open-label, pragmatic, randomized controlled trial and a parallel prospective (non-randomized) cohort study
primary purpose: Treatment
masking: None (Open Label)
measure: Hospital Mortality
time frame: 2 years
description: Does the use of inhaled volatile anesthetic-based sedation regimen improve participant hospital mortality as compared to standard intravenous sedation regimen with a 10% difference between groups for 752 participants.
measure: Ventilator-Free Days
time frame: 30 days
description: Does the use of inhaled volatile anesthetic-based sedation regimen improve participant ventilation outcomes after 30 days post enrollment, as compared to standard intravenous sedation regimen for 200 participants
measure: ICU-Free Days
time frame: 30 days
description: Does the use of inhaled volatile anesthetic-based sedation regimen improve participant time spent in ICU, 30 days post enrollment, as compared to standard intravenous sedation regimen for 128 participants
measure: Participant Quality of Life at 3 and 12 months after discharge
time frame: 365 days
description: Does the use of inhaled volatile anesthetic-based sedation regimen improve participant quality of life outcomes at 3 and 12 months post discharge as compared to standard intravenous sedation regimen for 144 participants. The EQ-5D questionnaire will be completed at both time points
measure: Median Daily Oxygenation
time frame: 3 days
description: To evaluate participant median daily oxygenation (PaO2/FiO2) at 3 days post enrollment
measure: Delirium and Coma Free Days
time frame: 14 days
description: To evaluate the days alive and free from delirium and coma while in ICU for 14 days after enrollment
measure: Adjunctive ARDS therapies
time frame: 30 days
description: To evaluate participant need for adjunctive ARDS therapies (prone, nitric oxide, paralysis, ECMO) during ICU stay
measure: Hospital-Free Days
time frame: 60 days
description: To evaluate the number of hospital-free days for participants, 60 days after enrollment
measure: Disability
time frame: 365 days
description: To evaluate participant disability at 3 and 12 months post discharge. The World Health Organization Disabiltity Assessment Score (WHODAS 2.0) will be completed at both timepoints. The scores assigned to each of the items - "none" (0), "mild" (1) "moderate" (2), "severe" (3) and "extreme" (4) - are summed. This method is referred to as simple scoring because the scores from each of the items are simply added up without recoding or collapsing of response categories; thus, there is no weighting of individual items.
arm group label: Inhaled - volatile anesthetic
arm group type: Experimental
description: The ICU patient will be randomized to either Isoflurane or Sevoflurane, whichever is available at the hospital. Dosage will be modified as per health care team guidance for the best treatment of the participant.
arm group label: Standard Care
arm group type: No Intervention
description: The ICU patient will be randomized to standard of care, which is any IV sedation supplied by the hospital. Dosage will be modified as per health care team guidance for the best treatment of the participant.
arm group label: Non-randomized
arm group type: No Intervention
description: In this arm, ICU patients who cannot be randomized will receive inhaled or IV sedation as per available in their unit. This is done to try to obtain the maximum amount of information available from the patients present to our ICUs.
intervention type: Drug
intervention name: Isoflurane Inhalant Product
description: Isoflurane will be administered using an inhalation device
arm group label: Inhaled - volatile anesthetic
intervention type: Drug
intervention name: Sevoflurane inhalant product
description: Sevoflurane will be administered using an inhalation device
arm group label: Inhaled - volatile anesthetic
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Angela Jerath, MD
phone: 416.480.6100
email: angela.jerath@sunnybrook.ca
last name: Iman Hussain
email: SAVE-ICU@sunnybrook.ca
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Canada
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Respiratory Insufficiency
mesh term: Sevoflurane
mesh term: Isoflurane
sharing ipd: No