<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/NCT04476979</url>
  </required_header>
  <id_info>
    <org_study_id>APHP200375-TOCIDEX</org_study_id>
    <secondary_id>2020-001246-18</secondary_id>
    <nct_id>NCT04476979</nct_id>
  </id_info>
  <brief_title>Comparison of Tocilizumab Plus Dexamethasone vs. Dexamethasone for Patients With Covid-19</brief_title>
  <acronym>TOCIDEX</acronym>
  <official_title>Comparison of Tocilizumab Plus Dexamethasone vs. Dexamethasone for Patients With Covid-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</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>
      The overall objective of the study is to determine the therapeutic effect and tolerance of&#xD;
      Tocilizumab combined with Dexamethasone in patients with moderate, severe pneumonia or&#xD;
      critical pneumonia associated with Coronavirus disease 2019 (COVID-19).&#xD;
&#xD;
      Tocilizumab (TCZ) is an anti-human IL-6 receptor monoclonal antibody that inhibits signal&#xD;
      transduction by binding sIL-6R and mIL-6R.&#xD;
&#xD;
      The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization&#xD;
      will occur prior to offering Dexamethasone alone or Dexamethasone +Tocilizumab administration&#xD;
      to patients enrolled in the CORIMUNO-19 cohort.&#xD;
&#xD;
      Tocilizumab will be administered to consenting adult patients hospitalized with COVID-19&#xD;
      either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or&#xD;
      critical pneumonia requiring mechanical ventilation.&#xD;
&#xD;
      Patients who will chose not to receive Tocilizumab will receive standard of cares.&#xD;
&#xD;
      Outcomes of Tocilizumab-treated patients will be compared with outcomes of standard of care&#xD;
      (including Dexamethasone) treated patients&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 16, 2020</start_date>
  <completion_date type="Actual">August 11, 2021</completion_date>
  <primary_completion_date type="Actual">June 1, 2021</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Survival without needs of invasive ventilation at day 14</measure>
    <time_frame>day 14</time_frame>
    <description>Survival without needs of invasive ventilation at day 14. Thus, events considered are mechanical (invasive) ventilation or death. A new DNR order will be considered as an event at the actual date of care limitation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>WHO progression scale at day 7 and 14</measure>
    <time_frame>day 7 and day 14</time_frame>
    <description>WHO progression scale:&#xD;
Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2&gt;=150 OR SpO2/FIO2&gt;=200: 7 Mechanical ventilation, (pO2/FIO2&lt;150 OR SpO2/FIO2&lt;200) OR vasopressors (norepinephrine &gt;0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2&lt;150 AND vasopressors (norepinephrine &gt;0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival at 14, 28, 60 and 90 days</measure>
    <time_frame>14, 28, 60 and 90 days</time_frame>
    <description>Overall survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of discharge alive at 14 and 28 days</measure>
    <time_frame>14 and 28 days</time_frame>
    <description>Cumulative incidence of discharge alive</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival without needs of mechanical ventilation at day 1</measure>
    <time_frame>day 1</time_frame>
    <description>Survival without needs of mechanical ventilation at day 1. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of oxygen supply independency at 14 and 28 days</measure>
    <time_frame>14 and 28 days</time_frame>
    <description>Cumulative incidence of oxygen supply independency</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival without needs of ventilator utilization at day 14</measure>
    <time_frame>14 days</time_frame>
    <description>Survival without needs of ventilator utilization (including non-invasive ventilation and Optiflow) at day 14</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">453</enrollment>
  <condition>Coronavirus Infection</condition>
  <condition>SARS (Severe Acute Respiratory Syndrome)</condition>
  <condition>Virus Diseases</condition>
  <condition>Coronaviridae Infections</condition>
  <condition>Nidovirales Infections</condition>
  <condition>RNA Virus Infections</condition>
  <condition>Respiratory Tract Infections</condition>
  <condition>Respiratory Tract Disease</condition>
  <arm_group>
    <arm_group_label>Dexamethasone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dexamethasone : 10 mg once daily for the first five days (day 1 to day 5) then 5 mg per day for up to 5 days, 2.5mg per day for up to 4 days (or until oxygen supply independency if sooner)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dexamethasone + Tocilizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dexamethasone : 10 mg once daily for the first five days (day 1 to day 5) then 5 mg per day for up to 5 days, 2.5mg per day for up to 4 days (or until oxygen supply independency if sooner)&#xD;
+Tocilizumab 8mg/kg D1 and if no response (No decrease of oxygen requirement) a second fixed dose of 400mg wil be administered at D3</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tocilizumab</intervention_name>
    <description>Tocilizumab 8mg/kg D1 and if no response (No decrease of oxygen requirement) a second fixed dose of 400mg wil be administered at D3</description>
    <arm_group_label>Dexamethasone + Tocilizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Dexamethasone : 10 mg once daily for the first five days (day 1 to day 5) then 5 mg per day for up to 5 days, 2.5mg per day for up to 4 days (or until oxygen supply independency if sooner)</description>
    <arm_group_label>Dexamethasone</arm_group_label>
    <arm_group_label>Dexamethasone + Tocilizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients included in the CORIMUNO-19 cohort&#xD;
&#xD;
          2. Patients belonging to the following group:&#xD;
&#xD;
               -  Requiring ≥ 3L/min of oxygen&#xD;
&#xD;
               -  WHO progression scale = 5&#xD;
&#xD;
               -  No NIV or High flow&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with exclusion criteria to the CORIMUNO-19 cohort.&#xD;
&#xD;
          -  Known hypersensitivity to Tocilizumab or DXM or to any of their excipients.&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Current documented bacterial infection not controlled by antibiotics.&#xD;
&#xD;
          -  certain evolving viral diseases (especially active herpes, chickenpox, shingles),&#xD;
&#xD;
          -  psychotic states still not controlled by treatment,&#xD;
&#xD;
          -  live vaccines in the previous 4 weeks,&#xD;
&#xD;
          -  Active tuberculosis or disseminated strongyloidiasis&#xD;
&#xD;
          -  Patient with any of following laboratory results out of the ranges detailed below at&#xD;
             screening should be discussed depending of the medication:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≤ 1.0 x 109/L&#xD;
&#xD;
               -  Haemoglobin level: no limitation&#xD;
&#xD;
               -  Platelets (PLT) &lt; 50 G /L&#xD;
&#xD;
               -  SGOT or SGPT &gt; 5N&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>CH Andrée Rosemon</name>
      <address>
        <city>Cayenne</city>
        <country>French Guiana</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>French Guiana</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>July 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>June 7, 2022</last_update_submitted>
  <last_update_submitted_qc>June 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 8, 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>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Virus Diseases</mesh_term>
    <mesh_term>Coronavirus Infections</mesh_term>
    <mesh_term>Respiratory Tract Infections</mesh_term>
    <mesh_term>Severe Acute Respiratory Syndrome</mesh_term>
    <mesh_term>RNA Virus Infections</mesh_term>
    <mesh_term>Coronaviridae Infections</mesh_term>
    <mesh_term>Nidovirales Infections</mesh_term>
    <mesh_term>Respiratory Tract Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</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/NCT04476979
org study id: APHP200375-TOCIDEX
secondary id: 2020-001246-18
nct id: NCT04476979
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The overall objective of the study is to determine the therapeutic effect and tolerance of
      Tocilizumab combined with Dexamethasone in patients with moderate, severe pneumonia or
      critical pneumonia associated with Coronavirus disease 2019 (COVID-19).

      Tocilizumab (TCZ) is an anti-human IL-6 receptor monoclonal antibody that inhibits signal
      transduction by binding sIL-6R and mIL-6R.

      The study has a cohort multiple Randomized Controlled Trials (cmRCT) design. Randomization
      will occur prior to offering Dexamethasone alone or Dexamethasone +Tocilizumab administration
      to patients enrolled in the CORIMUNO-19 cohort.

      Tocilizumab will be administered to consenting adult patients hospitalized with COVID-19
      either diagnosed with moderate or severe pneumonia requiring no mechanical ventilation or
      critical pneumonia requiring mechanical ventilation.

      Patients who will chose not to receive Tocilizumab will receive standard of cares.

      Outcomes of Tocilizumab-treated patients will be compared with outcomes of standard of care
      (including Dexamethasone) treated patients
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Survival without needs of invasive ventilation at day 14
time frame: day 14
description: Survival without needs of invasive ventilation at day 14. Thus, events considered are mechanical (invasive) ventilation or death. A new DNR order will be considered as an event at the actual date of care limitation.
measure: WHO progression scale at day 7 and 14
time frame: day 7 and day 14
description: WHO progression scale:
Uninfected; non viral RNA detected: 0 Asymptomatic; viral RNA detected: 1 Symptomatic; Independent: 2 Symptomatic; Assistance needed: 3 Hospitalized; No oxygen therapy: 4 Hospitalized; oxygen by mask or nasal prongs: 5 Hospitalized; oxygen by NIV or High flow: 6 Intubation and Mechanical ventilation, pO2/FIO2>=150 OR SpO2/FIO2>=200: 7 Mechanical ventilation, (pO2/FIO2<150 OR SpO2/FIO2<200) OR vasopressors (norepinephrine >0.3 microg/kg/min): 8 Mechanical ventilation, pO2/FIO2<150 AND vasopressors (norepinephrine >0.3 microg/kg/min), OR Dialysis OR ECMO: 9 Dead: 10
measure: Overall survival at 14, 28, 60 and 90 days
time frame: 14, 28, 60 and 90 days
description: Overall survival
measure: Cumulative incidence of discharge alive at 14 and 28 days
time frame: 14 and 28 days
description: Cumulative incidence of discharge alive
measure: Survival without needs of mechanical ventilation at day 1
time frame: day 1
description: Survival without needs of mechanical ventilation at day 1. New DNR order (if given after the inclusion of the patient) will be considered as an event at the date of the DNR.
measure: Cumulative incidence of oxygen supply independency at 14 and 28 days
time frame: 14 and 28 days
description: Cumulative incidence of oxygen supply independency
measure: Survival without needs of ventilator utilization at day 14
time frame: 14 days
description: Survival without needs of ventilator utilization (including non-invasive ventilation and Optiflow) at day 14
arm group label: Dexamethasone
arm group type: Active Comparator
description: Dexamethasone : 10 mg once daily for the first five days (day 1 to day 5) then 5 mg per day for up to 5 days, 2.5mg per day for up to 4 days (or until oxygen supply independency if sooner)
arm group label: Dexamethasone + Tocilizumab
arm group type: Experimental
description: Dexamethasone : 10 mg once daily for the first five days (day 1 to day 5) then 5 mg per day for up to 5 days, 2.5mg per day for up to 4 days (or until oxygen supply independency if sooner)
+Tocilizumab 8mg/kg D1 and if no response (No decrease of oxygen requirement) a second fixed dose of 400mg wil be administered at D3
intervention type: Drug
intervention name: Tocilizumab
description: Tocilizumab 8mg/kg D1 and if no response (No decrease of oxygen requirement) a second fixed dose of 400mg wil be administered at D3
arm group label: Dexamethasone + Tocilizumab
intervention type: Drug
intervention name: Dexamethasone
description: Dexamethasone : 10 mg once daily for the first five days (day 1 to day 5) then 5 mg per day for up to 5 days, 2.5mg per day for up to 4 days (or until oxygen supply independency if sooner)
arm group label: Dexamethasone
arm group label: Dexamethasone + Tocilizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: French Guiana
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Virus Diseases
mesh term: Coronavirus Infections
mesh term: Respiratory Tract Infections
mesh term: Severe Acute Respiratory Syndrome
mesh term: RNA Virus Infections
mesh term: Coronaviridae Infections
mesh term: Nidovirales Infections
mesh term: Respiratory Tract Diseases
mesh term: Dexamethasone
sharing ipd: Undecided