<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/NCT04486521</url>
  </required_header>
  <id_info>
    <org_study_id>RAC # 2201053</org_study_id>
    <nct_id>NCT04486521</nct_id>
  </id_info>
  <brief_title>Anti-IL6 and Corticosteroid Monotherapy vs Combination in COVID-19</brief_title>
  <official_title>Clinical Outcome of Anti-IL6 and Corticosteroid Monotherapy vs Combination in COVID-19 Cytokine Release Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>King Faisal Specialist Hospital &amp; Research Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Society of Critical Care Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>King Faisal Specialist Hospital &amp; Research Center</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The cytokine storms mediated by over production of proinflammatory cytokines have been&#xD;
      observed in a large population of critically ill patients infected with COVID-19. Patients&#xD;
      diagnosed with cytokine storms progress to cardiovascular collapse, multiple organ&#xD;
      dysfunction and death rapidly. Therefore, early identification, treatment and prevention of&#xD;
      the cytokine storms are of crucial importance for the patients. Immuomedulator such as&#xD;
      interleukin-6 (IL-6) antagonist, emerged as an alternative treatment for COVID-19 patients&#xD;
      with a risk of cytokine storms recently. In this study, we aimed to evaluate the safety and&#xD;
      efficacy of anti-IL6 alone vs anti-IL6 corticosteroid combination in patients with COVID-19&#xD;
      pneumonia&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will provide further insight whether anti-IL6 alone provide same efficacy and&#xD;
      clinical outcome with reasonable side effects profile compared to anti-IL6 + corticosteroid&#xD;
      and might serve as a corticosteroid sparing agents in COVID-19 patient with cytokine storms.&#xD;
      Data elements will be retrieved from VIRUS registry which is a prospective,&#xD;
      non-interventional, multi-center, multi-national observational cross sectional study&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 22, 2020</start_date>
  <completion_date type="Anticipated">July 22, 2021</completion_date>
  <primary_completion_date type="Anticipated">July 22, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Ventilator-Free Days</measure>
    <time_frame>Up to Day 28</time_frame>
    <description>The median ventilator-free days will be calculated as calendar days with no ventilator support to day 28 . Participants who die before day 28 are assigned zero free days.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median duration of ventilation</measure>
    <time_frame>Up to Day 28</time_frame>
    <description>From Intubation to extubation date and off Mechanical Ventilation or until ICU discharge, death, or 28 days whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median change in the PaO2/FiO2</measure>
    <time_frame>Up to Day 28</time_frame>
    <description>Ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vasopressor-Free days</measure>
    <time_frame>Up to Day 28</time_frame>
    <description>The median vasopressor-free days will be calculated as calendar days with no vasopressor support to day 28. Participants who die before day 28 are assigned zero free days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of ICU Stay</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>To compare ICU LOS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Hospital Stay</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>To compare hospital LOS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality Rate</measure>
    <time_frame>Up to Day 28</time_frame>
    <description>Death that occurs during 28 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of participants with adverse events [transaminitis, hyperglycemia]</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>adverse events that occurs during 28 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of Ferritin, IL6, D dimer, fibrinogen, C-reactive protein (CRP), Lactate dehydrogenase (LDH) and absolute lymphocyte count and their correlation with the effectiveness of the treatment</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Concentration of inflammatory markers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of superinfection (bacterial, viral, invasive fungal infections)</measure>
    <time_frame>Up to 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to the first COVID 19 test negative</measure>
    <time_frame>Up to 28 days</time_frame>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">860</enrollment>
  <condition>Critical Illness</condition>
  <condition>Corona Virus Infection</condition>
  <condition>Cytokine Release Syndrome</condition>
  <arm_group>
    <arm_group_label>Experimental</arm_group_label>
    <description>anti-IL-6 drugs (tocilizumab and siltuximab)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active Comparator 1</arm_group_label>
    <description>Anti-IL-6 drugs (tocilizumab and siltuximab) and corticosteroids combination</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active Comparator 2</arm_group_label>
    <description>corticosteroids alone</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Interleukin 6 (IL6) Antagonist</intervention_name>
    <description>anti-IL6 alone</description>
    <arm_group_label>Experimental</arm_group_label>
    <other_name>Tocilizumab</other_name>
    <other_name>Siltuximab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Interleukin 6 (IL6) Antagonist and corticosteroids</intervention_name>
    <description>anti-IL6 + corticosteroid combination</description>
    <arm_group_label>Active Comparator 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>corticosteroid alone</intervention_name>
    <description>dexamethasone, hydrocortisone, methylprednisolone, prednisone. All steroids &quot; other than dexamethasone&quot; will be converted to dexamethasone equivalent</description>
    <arm_group_label>Active Comparator 2</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Data elements will be retrieved from Viral Infection and Respiratory Illness Universal&#xD;
        Study: COVID-19 (VIRUS registry ClinicalTrials.gov Identifier: NCT04323787) which is a&#xD;
        prospective, non-interventional, multi-center, multi-national observational cross sectional&#xD;
        study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Adult Critically ill patients&#xD;
&#xD;
          2. COVID-19 PCR positive&#xD;
&#xD;
          3. Presence of clinical and radiological signs of progressive disease, and laboratory&#xD;
             evidence indicative of risk for cytokine storm complications.&#xD;
&#xD;
          4. Received anti-IL6 or corticosteroids as part of COVID-19 treatment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Non COVID-19 related admissions&#xD;
&#xD;
          2. Repeated Admission to ICUs/Hospital&#xD;
&#xD;
          3. Patient did not receive anti-IL6 or corticosteroids&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>14 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marwa Amer, PharmD,BCPS, BCCCP</last_name>
    <role>Principal Investigator</role>
    <affiliation>King Faisal Specialist Hospital and Research Center- Riyadh</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mohammed Bawazeer, MD,FRCSC,FACS</last_name>
    <role>Principal Investigator</role>
    <affiliation>King Faisal Specialist Hospital and Research Center- Riyadh</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marwa Amer, PharmD,BCPS, BCCCP</last_name>
    <phone>+966114647272</phone>
    <email>mamer@kfshrc.edu.sa</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Mohammed Bawazeer, MD,FRCSC,FACS</last_name>
    <phone>+966112162919</phone>
    <email>mbawazeer@kfshrc.edu.sa</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>King Faisal Specialist Hospital and Research Center</name>
      <address>
        <city>Riyadh</city>
        <country>Saudi Arabia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Abeer Omar</last_name>
      <email>ORA@kfshrc.edu.sa</email>
    </contact>
    <investigator>
      <last_name>Marwa Amer, PharmD, BCPS,BCCCP</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mohammed Bawazeer, MD, FRCSC, FACS</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Eiad Kseibi, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Talal Dahhan, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Abid Butt, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Syed Moazzum Khurshid, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Muath Rabee, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mohammed Abujazar, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Razan Alghunaim, PharmD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Maal Abualkhair, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Abeer AlFirm, Associate RC Data Manager</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Saudi Arabia</country>
  </location_countries>
  <reference>
    <citation>Walkey AJ, Kumar VK, Harhay MO, Bolesta S, Bansal V, Gajic O, Kashyap R. The Viral Infection and Respiratory Illness Universal Study (VIRUS): An International Registry of Coronavirus 2019-Related Critical Illness. Crit Care Explor. 2020 Apr 29;2(4):e0113. doi: 10.1097/CCE.0000000000000113. eCollection 2020 Apr.</citation>
    <PMID>32426754</PMID>
  </reference>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>March 4, 2021</last_update_submitted>
  <last_update_submitted_qc>March 4, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2021</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>Coronavirus Infections</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Critical Illness</mesh_term>
    <mesh_term>Cytokine Release Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Siltuximab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04486521
org study id: RAC # 2201053
nct id: NCT04486521
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
The cytokine storms mediated by over production of proinflammatory cytokines have been
      observed in a large population of critically ill patients infected with COVID-19. Patients
      diagnosed with cytokine storms progress to cardiovascular collapse, multiple organ
      dysfunction and death rapidly. Therefore, early identification, treatment and prevention of
      the cytokine storms are of crucial importance for the patients. Immuomedulator such as
      interleukin-6 (IL-6) antagonist, emerged as an alternative treatment for COVID-19 patients
      with a risk of cytokine storms recently. In this study, we aimed to evaluate the safety and
      efficacy of anti-IL6 alone vs anti-IL6 corticosteroid combination in patients with COVID-19
      pneumonia
This study will provide further insight whether anti-IL6 alone provide same efficacy and
      clinical outcome with reasonable side effects profile compared to anti-IL6 + corticosteroid
      and might serve as a corticosteroid sparing agents in COVID-19 patient with cytokine storms.
      Data elements will be retrieved from VIRUS registry which is a prospective,
      non-interventional, multi-center, multi-national observational cross sectional study
observational model: Other
time perspective: Prospective
measure: Ventilator-Free Days
time frame: Up to Day 28
description: The median ventilator-free days will be calculated as calendar days with no ventilator support to day 28 . Participants who die before day 28 are assigned zero free days.
measure: Median duration of ventilation
time frame: Up to Day 28
description: From Intubation to extubation date and off Mechanical Ventilation or until ICU discharge, death, or 28 days whichever occurs first.
measure: Median change in the PaO2/FiO2
time frame: Up to Day 28
description: Ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2)
measure: Vasopressor-Free days
time frame: Up to Day 28
description: The median vasopressor-free days will be calculated as calendar days with no vasopressor support to day 28. Participants who die before day 28 are assigned zero free days.
measure: Duration of ICU Stay
time frame: Up to 28 days
description: To compare ICU LOS
measure: Duration of Hospital Stay
time frame: Up to 28 days
description: To compare hospital LOS
measure: Mortality Rate
time frame: Up to Day 28
description: Death that occurs during 28 days
measure: Percentage of participants with adverse events [transaminitis, hyperglycemia]
time frame: Up to 28 days
description: adverse events that occurs during 28 days
measure: Concentration of Ferritin, IL6, D dimer, fibrinogen, C-reactive protein (CRP), Lactate dehydrogenase (LDH) and absolute lymphocyte count and their correlation with the effectiveness of the treatment
time frame: Up to 28 days
description: Concentration of inflammatory markers
measure: Rate of superinfection (bacterial, viral, invasive fungal infections)
time frame: Up to 28 days
measure: Time to the first COVID 19 test negative
time frame: Up to 28 days
arm group label: Experimental
description: anti-IL-6 drugs (tocilizumab and siltuximab)
arm group label: Active Comparator 1
description: Anti-IL-6 drugs (tocilizumab and siltuximab) and corticosteroids combination
arm group label: Active Comparator 2
description: corticosteroids alone
intervention type: Drug
intervention name: Interleukin 6 (IL6) Antagonist
description: anti-IL6 alone
arm group label: Experimental
other name: Tocilizumab
other name: Siltuximab
intervention type: Drug
intervention name: Interleukin 6 (IL6) Antagonist and corticosteroids
description: anti-IL6 + corticosteroid combination
arm group label: Active Comparator 1
intervention type: Drug
intervention name: corticosteroid alone
description: dexamethasone, hydrocortisone, methylprednisolone, prednisone. All steroids " other than dexamethasone" will be converted to dexamethasone equivalent
arm group label: Active Comparator 2
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 14 Years
maximum age: N/A
healthy volunteers: No
last name: Marwa Amer, PharmD,BCPS, BCCCP
role: Principal Investigator
affiliation: King Faisal Specialist Hospital and Research Center- Riyadh
last name: Mohammed Bawazeer, MD,FRCSC,FACS
role: Principal Investigator
affiliation: King Faisal Specialist Hospital and Research Center- Riyadh
last name: Marwa Amer, PharmD,BCPS, BCCCP
phone: +966114647272
email: mamer@kfshrc.edu.sa
last name: Mohammed Bawazeer, MD,FRCSC,FACS
phone: +966112162919
email: mbawazeer@kfshrc.edu.sa
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Saudi Arabia
citation: Walkey AJ, Kumar VK, Harhay MO, Bolesta S, Bansal V, Gajic O, Kashyap R. The Viral Infection and Respiratory Illness Universal Study (VIRUS): An International Registry of Coronavirus 2019-Related Critical Illness. Crit Care Explor. 2020 Apr 29;2(4):e0113. doi: 10.1097/CCE.0000000000000113. eCollection 2020 Apr.
PMID: 32426754
responsible party type: Sponsor
mesh term: Coronavirus Infections
mesh term: Syndrome
mesh term: Critical Illness
mesh term: Cytokine Release Syndrome
mesh term: Siltuximab
sharing ipd: Undecided