<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/NCT04477993</url>
  </required_header>
  <id_info>
    <org_study_id>32894720.3.0000.0068</org_study_id>
    <nct_id>NCT04477993</nct_id>
  </id_info>
  <brief_title>Ruxolitinib for Acute Respiratory Disorder Syndrome Due to COVID-19</brief_title>
  <acronym>RUXO-COVID</acronym>
  <official_title>Randomized, Double-Blind Clinical Trial of Ruxolitinib in Patients With Acute Respiratory Disorder Syndrome Due to SARS-CoV-2 Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderson Geraldo Rocha</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The COVID-19 pandemic has had a dramatic effect in public health worldwide. In Brazil, there&#xD;
      have been more than 2 million confirmed cases and over 75,000 deaths since February 26, 2020.&#xD;
      Based on reports of a hyperinflammatory state associated with COVID-19, the use of&#xD;
      immunosuppressive drugs may be efficacious in the treatment of this disease. JAK inhibitors&#xD;
      have been shown to harness inflammation in a number of different pathologic conditions. The&#xD;
      aim of the present study is to evaluate the efficacy and safety of JAK inhibitor ruxolitinib&#xD;
      in patients with acute respiratory distress syndrome due to COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low accrual&#xD;
  </why_stopped>
  <start_date type="Actual">August 14, 2020</start_date>
  <completion_date type="Actual">March 29, 2021</completion_date>
  <primary_completion_date type="Actual">March 29, 2021</primary_completion_date>
  <phase>Phase 2/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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>A composite outcome of death or ICU admission or mechanical ventilation at day 14.</measure>
    <time_frame>14 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>A composite outcome of death or ICU admission or mechanical ventilation at day 28</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to treatment failure</measure>
    <time_frame>28 days</time_frame>
    <description>ICU admission, mechanical ventilation, death or consent withdrawal</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival at days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of ICU admission rate at days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence of mechanical ventilation at days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of hospital stay</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of ICU stay</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of mechanical ventilation</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of non-invasive ventilation</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Secondary hemophagocytic syndrome rate</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative incidence nosocomial infection rate at days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of discontinuation of oxygen supplementation at days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of grade 1-2 and 3-5 emerging adverse events at day 28</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative dose of methylprednisolone at days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PaO2/FiO2 ratio from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in interleukin 6 levels [pg/mL] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in d-dimer levels [ng/mL] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in fibrinogen levels [mg/dL] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ferritin levels [ng/mL] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in C reactive protein levels [mg/L] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in alanine aminotransferase [U/L] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in aspartate aminotransferase [U/L] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in creatinine levels [mg/dL] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in glucose levels [mg/dL] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in hemoglobin levels [g/dL] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in platelet count [x10ˆ3/mmˆ3] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in absolute neutrophil count [x10ˆ3/mmˆ3] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in absolute neutrophil count [/mmˆ3] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in absolute lymphocyte count [/mmˆ3] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in prothrombin time ratio from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in partial thromboplastin time ratio from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in bilirubin [mg/dl] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in lactate dehydrogenase [U/L] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in CPK-MB [ng/mL] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in troponin [ng/mL] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in von Willebrand factor antigen level (VWF:Ag) [%] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in von Willebrand factor activity (ristocetin cofactor) [%] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ADAMTS-13 [%] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in von Willebrand multimeters from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in plasminogen activator inhibitor-1 levels [ng/mL] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in E-selectin levels [ng/mL] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in P-selectin levels [ng/mL] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in endothelin [fmol/mL] from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in circulating microparticles from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in thromboelastography from baseline to days 14 and 28</measure>
    <time_frame>14 and 28 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Severe Acute Respiratory Syndrome Coronavirus 2</condition>
  <condition>SARS-CoV2</condition>
  <arm_group>
    <arm_group_label>Experimental Group - ruxolitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ruxolitinib 5 mg PO b.i.d. for 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Janus Kinase Inhibitor (ruxolitinib)</intervention_name>
    <description>5 mg P.O. b.i.d. for 14 days. Dose reduction will occur if neutrophils &lt; 500/mm3 or platelets &lt;50,000/mm3.</description>
    <arm_group_label>Experimental Group - ruxolitinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo tablets P.O. b.i.d. for 14 days.</description>
    <arm_group_label>Placebo Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients hospitalized with SARS-CoV-2 pneumonia confirmed by RT-PCR or serology (IgA);&#xD;
&#xD;
          -  PaO2/FiO2 &lt; 300 (not fully explained by heart failure or volume overload) or SpO2 &lt;&#xD;
             90% on room air.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Symptom onset &gt; 14 days;&#xD;
&#xD;
          -  Neutrophil count &lt; 1,000/mm3;&#xD;
&#xD;
          -  Platelets &lt; 50,000/mm3;&#xD;
&#xD;
          -  ICU care at enrollment;&#xD;
&#xD;
          -  On invasive mechanical ventilation at enrollment;&#xD;
&#xD;
          -  Current use of experimental therapy for COVID-19 (except: azithromycin or&#xD;
             corticosteroids)&#xD;
&#xD;
          -  Uncontrolled arterial hypertension;&#xD;
&#xD;
          -  Current or previous use of systemic immunosuppressive therapy in the last 30 days;&#xD;
&#xD;
          -  Pregnancy or lactation;&#xD;
&#xD;
          -  Estimated creatinine clearance &lt; 30 mL/min or receiving CRRT or intermittent&#xD;
             hemodialysis;&#xD;
&#xD;
          -  Allergy to ruxolitinib;&#xD;
&#xD;
          -  Active tuberculosis;&#xD;
&#xD;
          -  HIV seropositivity;&#xD;
&#xD;
          -  Prior history of progressive multifocal leukoencephalopathy;&#xD;
&#xD;
          -  Use of any JAK inhibitor in the last 30 days before study enrollment;&#xD;
&#xD;
          -  Not qualifying according to investigators' perception.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>95 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hospital das Clínicas</name>
      <address>
        <city>Sao Paulo</city>
        <zip>05403-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</study_first_posted>
  <last_update_submitted>April 5, 2021</last_update_submitted>
  <last_update_submitted_qc>April 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Sao Paulo General Hospital</investigator_affiliation>
    <investigator_full_name>Vanderson Geraldo Rocha</investigator_full_name>
    <investigator_title>Full Professor</investigator_title>
  </responsible_party>
  <keyword>SARS-CoV2</keyword>
  <keyword>Severe Acute Respiratory Syndrome Coronavirus 2</keyword>
  <keyword>Janus Kinase Inhibitors</keyword>
  <keyword>Safety</keyword>
  <keyword>Clinical Efficacy</keyword>
  <keyword>Clinical Trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronavirus Infections</mesh_term>
    <mesh_term>Severe Acute Respiratory Syndrome</mesh_term>
    <mesh_term>Respiration Disorders</mesh_term>
    <mesh_term>Respiratory Tract Diseases</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Janus Kinase Inhibitors</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04477993
org study id: 32894720.3.0000.0068
nct id: NCT04477993
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The COVID-19 pandemic has had a dramatic effect in public health worldwide. In Brazil, there
      have been more than 2 million confirmed cases and over 75,000 deaths since February 26, 2020.
      Based on reports of a hyperinflammatory state associated with COVID-19, the use of
      immunosuppressive drugs may be efficacious in the treatment of this disease. JAK inhibitors
      have been shown to harness inflammation in a number of different pathologic conditions. The
      aim of the present study is to evaluate the efficacy and safety of JAK inhibitor ruxolitinib
      in patients with acute respiratory distress syndrome due to COVID-19.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: A composite outcome of death or ICU admission or mechanical ventilation at day 14.
time frame: 14 days
measure: A composite outcome of death or ICU admission or mechanical ventilation at day 28
time frame: 28 days
measure: Time to treatment failure
time frame: 28 days
description: ICU admission, mechanical ventilation, death or consent withdrawal
measure: Overall survival at days 14 and 28
time frame: 14 and 28 days
measure: Cumulative incidence of ICU admission rate at days 14 and 28
time frame: 14 and 28 days
measure: Cumulative incidence of mechanical ventilation at days 14 and 28
time frame: 14 and 28 days
measure: Duration of hospital stay
time frame: 28 days
measure: Duration of ICU stay
time frame: 28 days
measure: Duration of mechanical ventilation
time frame: 28 days
measure: Duration of non-invasive ventilation
time frame: 28 days
measure: Secondary hemophagocytic syndrome rate
time frame: 28 days
measure: Cumulative incidence nosocomial infection rate at days 14 and 28
time frame: 14 and 28 days
measure: Incidence of discontinuation of oxygen supplementation at days 14 and 28
time frame: 14 and 28 days
measure: Rate of grade 1-2 and 3-5 emerging adverse events at day 28
time frame: 28 days
measure: Cumulative dose of methylprednisolone at days 14 and 28
time frame: 14 and 28 days
measure: Change in PaO2/FiO2 ratio from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in interleukin 6 levels [pg/mL] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in d-dimer levels [ng/mL] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in fibrinogen levels [mg/dL] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in ferritin levels [ng/mL] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in C reactive protein levels [mg/L] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in alanine aminotransferase [U/L] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in aspartate aminotransferase [U/L] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in creatinine levels [mg/dL] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in glucose levels [mg/dL] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in hemoglobin levels [g/dL] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in platelet count [x10ˆ3/mmˆ3] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in absolute neutrophil count [x10ˆ3/mmˆ3] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in absolute neutrophil count [/mmˆ3] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in absolute lymphocyte count [/mmˆ3] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in prothrombin time ratio from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in partial thromboplastin time ratio from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in bilirubin [mg/dl] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in lactate dehydrogenase [U/L] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in CPK-MB [ng/mL] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in troponin [ng/mL] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in von Willebrand factor antigen level (VWF:Ag) [%] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in von Willebrand factor activity (ristocetin cofactor) [%] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in ADAMTS-13 [%] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in von Willebrand multimeters from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in plasminogen activator inhibitor-1 levels [ng/mL] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in E-selectin levels [ng/mL] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in P-selectin levels [ng/mL] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in endothelin [fmol/mL] from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in circulating microparticles from baseline to days 14 and 28
time frame: 14 and 28 days
measure: Change in thromboelastography from baseline to days 14 and 28
time frame: 14 and 28 days
arm group label: Experimental Group - ruxolitinib
arm group type: Experimental
description: Ruxolitinib 5 mg PO b.i.d. for 14 days
arm group label: Placebo Group
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Janus Kinase Inhibitor (ruxolitinib)
description: 5 mg P.O. b.i.d. for 14 days. Dose reduction will occur if neutrophils < 500/mm3 or platelets <50,000/mm3.
arm group label: Experimental Group - ruxolitinib
intervention type: Other
intervention name: Placebo
description: Placebo tablets P.O. b.i.d. for 14 days.
arm group label: Placebo Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 95 Years
healthy volunteers: No
facility: 
country: Brazil
responsible party type: Sponsor-Investigator
investigator affiliation: University of Sao Paulo General Hospital
investigator full name: Vanderson Geraldo Rocha
investigator title: Full Professor
mesh term: Coronavirus Infections
mesh term: Severe Acute Respiratory Syndrome
mesh term: Respiration Disorders
mesh term: Respiratory Tract Diseases
mesh term: Syndrome
mesh term: Janus Kinase Inhibitors