<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/NCT04412772</url>
  </required_header>
  <id_info>
    <org_study_id>RA-2020-019</org_study_id>
    <nct_id>NCT04412772</nct_id>
  </id_info>
  <brief_title>Trial of Tocilizumab for Treatment of Severe COVID-19: ARCHITECTS</brief_title>
  <acronym>ARCHITECTS</acronym>
  <official_title>A Randomized, Controlled Clinical Trial of the Safety and Efficacy of Tocilizumab for the Treatment of Severe COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Queen's Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Queen's Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall objective is to evaluate the clinical efficacy and safety of tocilizumab relative&#xD;
      to placebo among approximately 300 hospitalized adult patients who have severe COVID-19. The&#xD;
      study will be a 2 arm double blinded comparison between tocilizumab 8 mg/kg and matching&#xD;
      placebo IV. The dose may be repeated in 8-12 hours if clinical symptoms worsens, (e.g.&#xD;
      increase in oxygen requirements). Participants will be followed for 28 days.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 12, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2021</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical status (on a 7-point ordinal scale) at day 28</measure>
    <time_frame>up to day 28</time_frame>
    <description>Clinical Status 7-point ordinal scale:&#xD;
Not hospitalized, no limitations on activities&#xD;
Not hospitalized, limitation on activities&#xD;
Hospitalized, not requiring supplemental oxygen&#xD;
Hospitalized, requiring supplemental oxygen&#xD;
Hospitalized, on non-invasive ventilation or high flow oxygen devices&#xD;
Hospitalized, on invasive mechanical ventilation or ECMO&#xD;
Death</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical improvement</measure>
    <time_frame>up to day 28</time_frame>
    <description>ii. Time to clinical improvement, defined as a National Early Warning Score (NEWS) of &lt; 2 maintained for 24 hours iii. Time to clinical improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mechanical Ventilation</measure>
    <time_frame>up to day 28</time_frame>
    <description>iv. Incidence of mechanical ventilation v. Ventilator-free days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxygenation</measure>
    <time_frame>up to day 28</time_frame>
    <description>vi. Duration of time on supplemental oxygen</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Tocilizumab (TCZ) Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose may be given if clinical symptoms worsen.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose may be given if clinical symptoms worsen.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tocilizumab</intervention_name>
    <description>Participants will receive 1 dose of IV TCZ. 1 additional dose may be given if clinical symptoms worsen.</description>
    <arm_group_label>Tocilizumab (TCZ) Arm</arm_group_label>
    <other_name>Actemra</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will receive 1 dose of IV placebo matched to TCZ. Up to 1 additional dose may be given if clinical symptoms worsen.</description>
    <arm_group_label>Placebo Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ii. Hospitalized with COVID-19 pneumonia, based on chest X-ray or CT scan AND iii.&#xD;
             Evidence of hyperinflammation: IL-6&gt;40pg/mL (if available) OR CRP &gt;2 mg/dL OR ferritin&#xD;
             &gt;2000 ng/mL AND iv. One or more of the following: impending need for requiring&#xD;
             invasive or non-invasive mechanical ventilation OR shock requiring vasopressor&#xD;
             (without evidence of bacterial / fungal infection) OR need for extracorporeal membrane&#xD;
             oxygenation (ECMO) OR severe, refractor ARDS (PaO2/FiO2&lt;200 mmHg)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Known severe allergic reactions to tocilizumab or other monoclonal antibodies&#xD;
&#xD;
          -  Active tuberculosis infection based on history&#xD;
&#xD;
          -  Suspected active bacterial, fungal, viral, or other infection (besides COVID-19)&#xD;
&#xD;
          -  In the opinion of the investigator, progression to death is imminent and inevitable&#xD;
             within the next 24 hours, irrespective of the provision of treatments&#xD;
&#xD;
          -  Have received oral anti-rejection or immunomodulatory drugs (including tocilizumab)&#xD;
             with the past 6 months&#xD;
&#xD;
          -  Participating in other drug clinical trials (participation in COVID-19 trials allowed)&#xD;
&#xD;
          -  Self-reported pregnant or breastfeeding&#xD;
&#xD;
          -  Any serious medical condition or abnormality of clinical laboratory tests that, in the&#xD;
             investigator's judgment, precludes the patient's safe participation in and completion&#xD;
             of the study&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) &gt; 10 x upper limit&#xD;
             of normal (ULN) detected within 24 hours at baseline&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &lt; 1000/mL at baseline&#xD;
&#xD;
          -  Platelet count &lt; 50,000/mL at baseline&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>95 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Todd Seto, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Queen's Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Todd Seto, MD</last_name>
    <phone>808 354-3533</phone>
    <email>tseto@queens.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>May Vawer, RN</last_name>
    <phone>808 691-7185</phone>
    <email>mvawer@queens.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Queen's Medical Center</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96813</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Todd Seto, MD</last_name>
      <phone>808-354-3533</phone>
      <email>tseto@queens.org</email>
    </contact>
    <contact_backup>
      <last_name>May Vawer, RN</last_name>
      <phone>808 691-7185</phone>
      <email>mvawer@queens.org</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>November 13, 2020</last_update_submitted>
  <last_update_submitted_qc>November 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 17, 2020</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>COVID-19</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/NCT04412772
org study id: RA-2020-019
nct id: NCT04412772
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The overall objective is to evaluate the clinical efficacy and safety of tocilizumab relative
      to placebo among approximately 300 hospitalized adult patients who have severe COVID-19. The
      study will be a 2 arm double blinded comparison between tocilizumab 8 mg/kg and matching
      placebo IV. The dose may be repeated in 8-12 hours if clinical symptoms worsens, (e.g.
      increase in oxygen requirements). Participants will be followed for 28 days.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Clinical status (on a 7-point ordinal scale) at day 28
time frame: up to day 28
description: Clinical Status 7-point ordinal scale:
Not hospitalized, no limitations on activities
Not hospitalized, limitation on activities
Hospitalized, not requiring supplemental oxygen
Hospitalized, requiring supplemental oxygen
Hospitalized, on non-invasive ventilation or high flow oxygen devices
Hospitalized, on invasive mechanical ventilation or ECMO
Death
measure: Clinical improvement
time frame: up to day 28
description: ii. Time to clinical improvement, defined as a National Early Warning Score (NEWS) of < 2 maintained for 24 hours iii. Time to clinical improvement of at least 2 categories relative to baseline on a 7-category ordinal scale of clinical status
measure: Mechanical Ventilation
time frame: up to day 28
description: iv. Incidence of mechanical ventilation v. Ventilator-free days
measure: Oxygenation
time frame: up to day 28
description: vi. Duration of time on supplemental oxygen
arm group label: Tocilizumab (TCZ) Arm
arm group type: Experimental
description: Participants will receive 1 intravenous (IV) infusion of TCZ, dosed at 8 mg/kg, up to a maximum dose 800 mg. Up to 1 additional dose may be given if clinical symptoms worsen.
arm group label: Placebo Arm
arm group type: Placebo Comparator
description: Participants will receive 1 IV infusion of placebo matched to TCZ. Up to 1 additional dose may be given if clinical symptoms worsen.
intervention type: Drug
intervention name: Tocilizumab
description: Participants will receive 1 dose of IV TCZ. 1 additional dose may be given if clinical symptoms worsen.
arm group label: Tocilizumab (TCZ) Arm
other name: Actemra
intervention type: Drug
intervention name: Placebo
description: Participants will receive 1 dose of IV placebo matched to TCZ. Up to 1 additional dose may be given if clinical symptoms worsen.
arm group label: Placebo Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 95 Years
healthy volunteers: No
last name: Todd Seto, MD
role: Principal Investigator
affiliation: The Queen's Medical Center
last name: Todd Seto, MD
phone: 808 354-3533
email: tseto@queens.org
last name: May Vawer, RN
phone: 808 691-7185
email: mvawer@queens.org
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: No