<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/NCT04472611</url>
  </required_header>
  <id_info>
    <org_study_id>2000027950</org_study_id>
    <nct_id>NCT04472611</nct_id>
  </id_info>
  <brief_title>Colchicine/Statins for the Prevention of COVID-19 Complications (COLSTAT) Trial</brief_title>
  <acronym>COLSTAT</acronym>
  <official_title>Colchicine/Statins for the Prevention of COVID-19 Complications (COLSTAT) Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yale University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pragmatic randomized open-label study of the safety and efficacy of the combination&#xD;
      of colchicine and Rosuvastatin in addition to standard of care (SOC) compared to SOC alone in&#xD;
      hospitalized patients with SARS-CoV-2&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective 1:1 randomized open-label clinical trial to investigate the safety and&#xD;
      efficacy of the combination of Colchicine + Rosuvastatin added to standard of care (SOC)&#xD;
      compared to SOC alone in hospitalized subjects with moderate COVID-19.&#xD;
&#xD;
      Subjects will be screened during admission to hospital. Patients with confirmed SARS-CoV-2&#xD;
      infection, and meeting all other inclusion and exclusion criteria, will be randomized to&#xD;
      either Colchicine+Rosuvastatin treatment or SOC for the duration of hospitalization. SOC will&#xD;
      be guided by the YNHH SARS-CoV-2 Therapeutics Group. In cases where patients require&#xD;
      randomization in another trial evaluating an experimental drug, they will continue on study&#xD;
      drug. Patients will be assessed daily while hospitalized for clinical, biomarker, safety, and&#xD;
      laboratory parameters based on SOC.&#xD;
&#xD;
      Colchicine is an extensively studied oral anti-inflammatory agent with a well-defined safety&#xD;
      profile. Colchicine, by inhibiting tubulin polymerization and clathrin-mediated endocytosis&#xD;
      has the potential to inhibit SARS-CoV-2 cell entry. In addition, colchicine has a direct&#xD;
      anti-inflammatory effect by inhibiting the NLRP3 inflammasome activation which in turn has&#xD;
      the potential to reduce the SARS-CoV-2-induced cytokine storm. Statins also have direct&#xD;
      anti-inflammatory effects by reducing chemokine release, adhesion molecules, and modulating T&#xD;
      cell activity and have the potential to prevent SARS-CoV-2 related endothelial dysfunction&#xD;
      and may reduce the morbidity and mortality associated with COVID-19. Rosuvastatin, in&#xD;
      particular, appears to have direct antiviral properties by binding and inhibiting the active&#xD;
      site of the main protease enzyme (Mpro) of SARS-CoV-2.1&#xD;
&#xD;
      The combination Colchicine + Rosuvastatin may have a synergetic effect to antagonize&#xD;
      SARS-CoV-2 infection, modulate the inflammatory response and to reduce morbidity and&#xD;
      mortality associated with acute respiratory distress syndrome (ARDS) and myocardial injury in&#xD;
      COVID-19 patients.&#xD;
&#xD;
      Both drugs have been in use for decades for gout and pericarditis (colchicine) and&#xD;
      hyperlipidemia, coronary disease (CAD) and diabetes (rosuvastatin/Crestor), and have been&#xD;
      tested in thousands of patients used individually and in combination with a low and well&#xD;
      characterized risk profile. Colchicine and rosuvastatin are currently used as standard of&#xD;
      care in COVID-19 patients whether due to pre-existing CAD, gout or pericarditis or acute&#xD;
      presentations with acute coronary syndromes or acute gout with no expected added risk in the&#xD;
      population being studied.&#xD;
&#xD;
      This study is not intended to support a labeling change or advertising claim for either drug,&#xD;
      and the study will be conducted in compliance with the requirements of Yale University's IRB&#xD;
      review and a research IND.&#xD;
&#xD;
      Subjects will be screened within 48 hours of hospital admission. Patients with real-time&#xD;
      reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infection and&#xD;
      meeting all inclusion and exclusion criteria, will be randomized to either Colchicine +&#xD;
      Rosuvastatin treatment in addition to SOC or SOC alone for the duration of hospitalization.&#xD;
&#xD;
      Subjects will be randomized in a 1:1 manner to one of two arms:&#xD;
&#xD;
      Active treatment:&#xD;
&#xD;
      In addition to SOC* subjects randomized to active treatment will receive:&#xD;
&#xD;
        -  Rosuvastatin: 40mg daily AND&#xD;
&#xD;
        -  Colchicine: 0.6mg twice daily for 3 days then 0.6mg daily Note: Dose adjustment based on&#xD;
           medical conditions and drug interactions (see section §7.4.1). Subjects previously on&#xD;
           chronic statin therapy will be eligible for enrollment in the trial, and if randomized&#xD;
           to active treatment, chronic statin therapy will be discontinued and replaced by&#xD;
           rosuvastatin 40 mg for 30 days or hospital discharge and resumed thereafter.&#xD;
&#xD;
      Standard of Care Controls:&#xD;
&#xD;
      Subjects will undergo SOC treatment determined by the primary care team and the YNHH&#xD;
      treatment algorithm for hospitalized patients with COVID-19.&#xD;
&#xD;
      *All standard of care treatments for hospitalized subjects with SARS-CoV-2 are permitted&#xD;
      concurrently with the study intervention. This only includes treatments approved by the Yale&#xD;
      SOC treatment Committee. Concomitant therapy will be performed according to standard&#xD;
      practice, local standards of care and published guidelines. Subjects will not be permitted to&#xD;
      participate in other investigational studies. Methods for identifying drug interactions and&#xD;
      dose adjustment are listed in section §7.4.1 of the protocol. Drug discontinuation is only&#xD;
      permitted with documented adverse reactions (section §7.4.3).&#xD;
&#xD;
      Treatment will continue for a total of 30 days. If the subject is discharged the treatment&#xD;
      will stop at that time.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 30, 2020</start_date>
  <completion_date type="Actual">March 30, 2022</completion_date>
  <primary_completion_date type="Actual">March 30, 2022</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With COVID 19 Severity</measure>
    <time_frame>30 Days</time_frame>
    <description>As defined by World Health Organization Ordinal Scale, which ranges from 1 to 8. Severity of COVID measured by WHO Scores 5-8: Defined as 5= Hospitalized requiring including CPAP, face mask, high flow nasal cannula (Excludes regular nasal cannula), 6= Hospitalized requiring intubation and mechanical ventilation, 7= Hospitalized requiring mechanical ventilation and additional organ support (vasopressors, renal replacement therapy, ECMO), 8= Death. Data presented is for Max WHO scores 5-8, indicating moderately to severely infected participants.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">250</enrollment>
  <condition>SARS-CoV-2</condition>
  <arm_group>
    <arm_group_label>Standard of Care (SOC) and Colchicine+Rosuvastatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will take Rosuvastatin 40mg daily and Colchicine 0.6mg twice for 3 days and then 0.6mg daily during hospitalization</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard of care (SOC)</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Patients will undergo standard of care treatment during hospitalization determined by the primary care team during hospitalization</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard of Care (SOC) and Colchicine+Rosuvastatin</intervention_name>
    <description>Patients will take Rosuvastatin 40mg daily and Colchicine 0.6mg twice for 3 days and then 0.6mg daily during hospitalization</description>
    <arm_group_label>Standard of Care (SOC) and Colchicine+Rosuvastatin</arm_group_label>
    <other_name>SOC &amp; Colchicine and Rosuvastatin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria 1.18 years or older and confirmed SARS-CoV-2 infection by RT-PCR 2.&#xD;
        Patient is admitted to the floor (non-ICU) within 48 hours of hospital admission 3. The&#xD;
        patient, or legally authorized representative, has been informed of the nature of the&#xD;
        study, agrees to its provisions and has provided witnessed (by 2 independent members of the&#xD;
        health care team) oral informed consent, or a photograph of the signed informed consent&#xD;
        approved by the Institutional Review Board (IRB)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known pregnancy or nursing mothers&#xD;
&#xD;
          2. Known allergy to statins or colchicine&#xD;
&#xD;
          3. Patient is on chronic colchicine or oral corticosteroid treatment&#xD;
&#xD;
          4. Acute liver disease defined by elevated transaminases (AST/ALT &gt; 3x ULN)&#xD;
&#xD;
          5. Severe chronic kidney disease defined as glomerular filtration rate (GFR) &lt;&#xD;
             30mL/min1.73 m2&#xD;
&#xD;
          6. Severe QTc prolongation (&gt;500ms narrow QRS&lt;120ms and &gt;550ms for wide QRS&gt;120)&#xD;
&#xD;
          7. Presents with severe disease on admission (WHO ordinal scale of clinical improvement&#xD;
             scores 5-8)&#xD;
&#xD;
          8. Rhabdomyolysis or CPK &gt; 5x ULN&#xD;
&#xD;
          9. Thrombocytopenia defined as platelet count &lt; 50,000 / mm3&#xD;
&#xD;
         10. Leukopenia defined as white blood cell count &lt; 3000 ml&#xD;
&#xD;
         11. Severe anemia defined as Hemoglobin value &lt;8 g/100ml&#xD;
&#xD;
         12. Participation in any other clinical trial of an experimental treatment for COVID-19&#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_official>
    <last_name>Alexandra Lansky, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Bridgeport Hospital</name>
      <address>
        <city>Bridgeport</city>
        <state>Connecticut</state>
        <zip>06610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenwich Hospital</name>
      <address>
        <city>Greenwich</city>
        <state>Connecticut</state>
        <zip>06807</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale New Haven Hosptial System</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06512</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lawrence &amp; Memorial Hospital</name>
      <address>
        <city>New London</city>
        <state>Connecticut</state>
        <zip>06320</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <results_first_submitted>December 20, 2022</results_first_submitted>
  <results_first_submitted_qc>April 25, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">April 27, 2023</results_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>Rosuvastatin</keyword>
  <keyword>Colchicine</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colchicine</mesh_term>
    <mesh_term>Rosuvastatin Calcium</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 8, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/11/NCT04472611/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 6, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/11/NCT04472611/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Standard of Care (SOC) and Colchicine+Rosuvastatin</title>
          <description>Patients will take Rosuvastatin 40mg daily and Colchicine 0.6mg twice for 3 days and then 0.6mg daily during hospitalization&#xD;
Standard of Care (SOC) and Colchicine+Rosuvastatin: Patients will take Rosuvastatin 40mg daily and Colchicine 0.6mg twice for 3 days and then 0.6mg daily during hospitalization</description>
        </group>
        <group group_id="P2">
          <title>Standard of Care (SOC)</title>
          <description>Patients will undergo standard of care treatment during hospitalization determined by the primary care team during hospitalization</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="125"/>
                <participants group_id="P2" count="125"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="122"/>
                <participants group_id="P2" count="125"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Patients hospitalized with moderate to severe symptoms of COVID being treated with standard protocol medications as set by hospital</population>
      <group_list>
        <group group_id="B1">
          <title>SOC and Colchicine and Rosuvastatin</title>
          <description>Patients will take Rosuvastatin 40mg daily and Colchicine 0.6mg twice for 3 days and then 0.6mg daily during hospitalization</description>
        </group>
        <group group_id="B2">
          <title>Standard of Care (SOC)</title>
          <description>Patients will undergo standard of care treatment during hospitalization determined by the primary care team during hospitalization</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="125"/>
            <count group_id="B2" value="125"/>
            <count group_id="B3" value="250"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Age 18+ hospitalized with COVID No liver, kidney issues</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="74"/>
                    <measurement group_id="B2" value="77"/>
                    <measurement group_id="B3" value="151"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60.4" spread="14.6"/>
                    <measurement group_id="B2" value="62.4" spread="16.1"/>
                    <measurement group_id="B3" value="61.4" spread="15.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="69"/>
                    <measurement group_id="B2" value="55"/>
                    <measurement group_id="B3" value="124"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="56"/>
                    <measurement group_id="B2" value="70"/>
                    <measurement group_id="B3" value="126"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="76"/>
                    <measurement group_id="B2" value="81"/>
                    <measurement group_id="B3" value="157"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="51"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="125"/>
                    <measurement group_id="B2" value="125"/>
                    <measurement group_id="B3" value="250"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With COVID 19 Severity</title>
        <description>As defined by World Health Organization Ordinal Scale, which ranges from 1 to 8. Severity of COVID measured by WHO Scores 5-8: Defined as 5= Hospitalized requiring including CPAP, face mask, high flow nasal cannula (Excludes regular nasal cannula), 6= Hospitalized requiring intubation and mechanical ventilation, 7= Hospitalized requiring mechanical ventilation and additional organ support (vasopressors, renal replacement therapy, ECMO), 8= Death. Data presented is for Max WHO scores 5-8, indicating moderately to severely infected participants.</description>
        <time_frame>30 Days</time_frame>
        <population>Moderately infected COVID patients requiring hospitalization.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard of Care (SOC) and Colchicine+Rosuvastatin</title>
            <description>Patients will take Rosuvastatin 40mg daily and Colchicine 0.6mg twice for 3 days and then 0.6mg daily during hospitalization&#xD;
Standard of Care (SOC) and Colchicine+Rosuvastatin: Patients will take Rosuvastatin 40mg daily and Colchicine 0.6mg twice for 3 days and then 0.6mg daily during hospitalization</description>
          </group>
          <group group_id="O2">
            <title>Standard of Care (SOC)</title>
            <description>Patients will undergo standard of care treatment during hospitalization determined by the primary care team during hospitalization</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With COVID 19 Severity</title>
          <description>As defined by World Health Organization Ordinal Scale, which ranges from 1 to 8. Severity of COVID measured by WHO Scores 5-8: Defined as 5= Hospitalized requiring including CPAP, face mask, high flow nasal cannula (Excludes regular nasal cannula), 6= Hospitalized requiring intubation and mechanical ventilation, 7= Hospitalized requiring mechanical ventilation and additional organ support (vasopressors, renal replacement therapy, ECMO), 8= Death. Data presented is for Max WHO scores 5-8, indicating moderately to severely infected participants.</description>
          <population>Moderately infected COVID patients requiring hospitalization.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Max WHO score 5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Max WHO score 6</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Max WHO score 7</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Max WHO score 8</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were recorded for patients starting at date/time of enrollment through study exit at 60 day post-discharge timepoint.</time_frame>
      <desc>Adverse events were recorded for patients starting at date/time of enrollment through study exit at 60 day post-discharge timepoint, up to a maximum of 90 days.</desc>
      <group_list>
        <group group_id="E1">
          <title>Standard of Care (SOC) and Colchicine+Rosuvastatin</title>
          <description>Patients will take Rosuvastatin 40mg daily and Colchicine 0.6mg twice for 3 days and then 0.6mg daily during hospitalization&#xD;
Standard of Care (SOC) and Colchicine+Rosuvastatin: Patients will take Rosuvastatin 40mg daily and Colchicine 0.6mg twice for 3 days and then 0.6mg daily during hospitalization</description>
        </group>
        <group group_id="E2">
          <title>Standard of Care (SOC)</title>
          <description>Patients will undergo standard of care treatment during hospitalization determined by the primary care team during hospitalization</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="125"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="125"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <description>Respiratory failure</description>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="125"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="125"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="125"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="125"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal Distress</sub_title>
                <description>Diarrhea</description>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="125"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="125"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Increased Liver Function Tests</sub_title>
                <description>Increased amount of liver function test values</description>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="125"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="125"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Alexandra Lansky</name_or_title>
      <organization>Yale University School of Medicine</organization>
      <phone>203 737 2142</phone>
      <email>alexandra.lansky@yale.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04472611
org study id: 2000027950
nct id: NCT04472611
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a pragmatic randomized open-label study of the safety and efficacy of the combination
      of colchicine and Rosuvastatin in addition to standard of care (SOC) compared to SOC alone in
      hospitalized patients with SARS-CoV-2
This is a prospective 1:1 randomized open-label clinical trial to investigate the safety and
      efficacy of the combination of Colchicine + Rosuvastatin added to standard of care (SOC)
      compared to SOC alone in hospitalized subjects with moderate COVID-19.

      Subjects will be screened during admission to hospital. Patients with confirmed SARS-CoV-2
      infection, and meeting all other inclusion and exclusion criteria, will be randomized to
      either Colchicine+Rosuvastatin treatment or SOC for the duration of hospitalization. SOC will
      be guided by the YNHH SARS-CoV-2 Therapeutics Group. In cases where patients require
      randomization in another trial evaluating an experimental drug, they will continue on study
      drug. Patients will be assessed daily while hospitalized for clinical, biomarker, safety, and
      laboratory parameters based on SOC.

      Colchicine is an extensively studied oral anti-inflammatory agent with a well-defined safety
      profile. Colchicine, by inhibiting tubulin polymerization and clathrin-mediated endocytosis
      has the potential to inhibit SARS-CoV-2 cell entry. In addition, colchicine has a direct
      anti-inflammatory effect by inhibiting the NLRP3 inflammasome activation which in turn has
      the potential to reduce the SARS-CoV-2-induced cytokine storm. Statins also have direct
      anti-inflammatory effects by reducing chemokine release, adhesion molecules, and modulating T
      cell activity and have the potential to prevent SARS-CoV-2 related endothelial dysfunction
      and may reduce the morbidity and mortality associated with COVID-19. Rosuvastatin, in
      particular, appears to have direct antiviral properties by binding and inhibiting the active
      site of the main protease enzyme (Mpro) of SARS-CoV-2.1

      The combination Colchicine + Rosuvastatin may have a synergetic effect to antagonize
      SARS-CoV-2 infection, modulate the inflammatory response and to reduce morbidity and
      mortality associated with acute respiratory distress syndrome (ARDS) and myocardial injury in
      COVID-19 patients.

      Both drugs have been in use for decades for gout and pericarditis (colchicine) and
      hyperlipidemia, coronary disease (CAD) and diabetes (rosuvastatin/Crestor), and have been
      tested in thousands of patients used individually and in combination with a low and well
      characterized risk profile. Colchicine and rosuvastatin are currently used as standard of
      care in COVID-19 patients whether due to pre-existing CAD, gout or pericarditis or acute
      presentations with acute coronary syndromes or acute gout with no expected added risk in the
      population being studied.

      This study is not intended to support a labeling change or advertising claim for either drug,
      and the study will be conducted in compliance with the requirements of Yale University's IRB
      review and a research IND.

      Subjects will be screened within 48 hours of hospital admission. Patients with real-time
      reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infection and
      meeting all inclusion and exclusion criteria, will be randomized to either Colchicine +
      Rosuvastatin treatment in addition to SOC or SOC alone for the duration of hospitalization.

      Subjects will be randomized in a 1:1 manner to one of two arms:

      Active treatment:

      In addition to SOC* subjects randomized to active treatment will receive:

        -  Rosuvastatin: 40mg daily AND

        -  Colchicine: 0.6mg twice daily for 3 days then 0.6mg daily Note: Dose adjustment based on
           medical conditions and drug interactions (see section §7.4.1). Subjects previously on
           chronic statin therapy will be eligible for enrollment in the trial, and if randomized
           to active treatment, chronic statin therapy will be discontinued and replaced by
           rosuvastatin 40 mg for 30 days or hospital discharge and resumed thereafter.

      Standard of Care Controls:

      Subjects will undergo SOC treatment determined by the primary care team and the YNHH
      treatment algorithm for hospitalized patients with COVID-19.

      *All standard of care treatments for hospitalized subjects with SARS-CoV-2 are permitted
      concurrently with the study intervention. This only includes treatments approved by the Yale
      SOC treatment Committee. Concomitant therapy will be performed according to standard
      practice, local standards of care and published guidelines. Subjects will not be permitted to
      participate in other investigational studies. Methods for identifying drug interactions and
      dose adjustment are listed in section §7.4.1 of the protocol. Drug discontinuation is only
      permitted with documented adverse reactions (section §7.4.3).

      Treatment will continue for a total of 30 days. If the subject is discharged the treatment
      will stop at that time.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With COVID 19 Severity
time frame: 30 Days
description: As defined by World Health Organization Ordinal Scale, which ranges from 1 to 8. Severity of COVID measured by WHO Scores 5-8: Defined as 5= Hospitalized requiring including CPAP, face mask, high flow nasal cannula (Excludes regular nasal cannula), 6= Hospitalized requiring intubation and mechanical ventilation, 7= Hospitalized requiring mechanical ventilation and additional organ support (vasopressors, renal replacement therapy, ECMO), 8= Death. Data presented is for Max WHO scores 5-8, indicating moderately to severely infected participants.
arm group label: Standard of Care (SOC) and Colchicine+Rosuvastatin
arm group type: Experimental
description: Patients will take Rosuvastatin 40mg daily and Colchicine 0.6mg twice for 3 days and then 0.6mg daily during hospitalization
arm group label: Standard of care (SOC)
arm group type: No Intervention
description: Patients will undergo standard of care treatment during hospitalization determined by the primary care team during hospitalization
intervention type: Drug
intervention name: Standard of Care (SOC) and Colchicine+Rosuvastatin
description: Patients will take Rosuvastatin 40mg daily and Colchicine 0.6mg twice for 3 days and then 0.6mg daily during hospitalization
arm group label: Standard of Care (SOC) and Colchicine+Rosuvastatin
other name: SOC & Colchicine and Rosuvastatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Alexandra Lansky, MD
role: Principal Investigator
affiliation: Yale University
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Colchicine
mesh term: Rosuvastatin Calcium
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 