<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/NCT04401423</url>
  </required_header>
  <id_info>
    <org_study_id>AAAT0535</org_study_id>
    <nct_id>NCT04401423</nct_id>
  </id_info>
  <brief_title>TXA127 for the Treatment of Severe COVID-19</brief_title>
  <official_title>Randomized Controlled Trial of Angiotensin 1-7 (TXA127) for the Treatment of Severe COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Constant Therapeutics LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Columbia 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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if administration of angiotensin-(1-7) (TXA127)&#xD;
      prevents acute kidney injury and deterioration into multi-organ failure in patients with&#xD;
      severe COVID-19. Participants will undergo a 10-day treatment with either placebo or study&#xD;
      drug. The drug will be administered intravenously for 3 hours once each day for 10 days&#xD;
      consecutively.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Corona virus disease 2019 (COVID-19) has been associated with severe respiratory and&#xD;
      multiorgan failure. Research shows that COVID-19 reduces levels of angiotensin-converting&#xD;
      enzyme-2 (ACE-2), an enzyme that converts angiotensin II to angiotensin 1-7 (known as&#xD;
      TXA127). COVID-19 reduces levels of ACE-2 and therefore angiotensin 1-7 and as a result,&#xD;
      angiotensin II levels are going to be increased. Many clinical observations in COVID-19 have&#xD;
      shown the high incidence of acute kidney injury that may be due to excessive levels of&#xD;
      angiotensin II. The investigators hypothesize that administration of angiotensin (1-7)&#xD;
      replaces levels of ACE-2 in COVID-19 and thereby ameliorates deterioration of multi-organ&#xD;
      failure and specifically acute kidney injury.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 10, 2021</start_date>
  <completion_date type="Actual">June 10, 2021</completion_date>
  <primary_completion_date type="Actual">June 10, 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>
    <intervention_model_description>Double-blinded, placebo-control, randomized clinical trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of Serum Creatinine</measure>
    <time_frame>Day 1 and Day 10</time_frame>
    <description>Calculated from baseline (at enrollment) to end of study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants Requiring Intubation</measure>
    <time_frame>From Day 1 to Day 10</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Requiring Dialysis</measure>
    <time_frame>Up to Day 10</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Requiring a Vasopressors</measure>
    <time_frame>Up to Day 10</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in Supplemental Oxygen Requirements</measure>
    <time_frame>Day 1 and Day 10</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days of Hospital Stay and Drug Administration</measure>
    <time_frame>Day 1 to Day 10</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine Levels on the Day of Drug/TXA Administration</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cytokine Levels on the Day 5 of Drug/TXA Administration</measure>
    <time_frame>Day 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>Day 1 to Day 10</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>TXA127</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TXA127</intervention_name>
    <description>0.5 mg/kg per day</description>
    <arm_group_label>TXA127</arm_group_label>
    <other_name>angiotensin-(1-7)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>0.5 mg/kg per day</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>control</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Severe COVID-19: Adult patients admitted to the hospital through the Emergency&#xD;
             Department (ED) requiring oxygen therapy (any level) to maintain oxygen saturation&#xD;
             (SaO2) &gt; 90%&#xD;
&#xD;
          -  COVID positive by polymerase chain reaction (PCR) on hospital admission&#xD;
&#xD;
          -  Hospitalized patients aged 18 years or greater&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pre-existing chronic kidney disease&#xD;
&#xD;
          -  New use of or change in dose of ACE-inhibitors or angiotensin receptor blocker (ARB)&#xD;
             within the last 6 months&#xD;
&#xD;
          -  Acute kidney injury at the time of enrollment defined as either increase pf serum&#xD;
             creatinine by more than 50% or 0.3 mg/dL above baseline or estimated creatinine&#xD;
             clearance (by MDRD) of less than 60 ml/min (if no baseline serum creatinine available)&#xD;
&#xD;
          -  Pregnant and breastfeeding women&#xD;
&#xD;
          -  Contraindicated medications: new use or change of medications from start of trial&#xD;
             (start of an ACE inhibitor or ARB within 6 months of trial).&#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>Jeanine D'Armiento, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Associate Professor of Medicine in Anesthesiology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Columbia University Irving Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>May 21, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <results_first_submitted>May 9, 2022</results_first_submitted>
  <results_first_submitted_qc>July 4, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">July 27, 2022</results_first_posted>
  <last_update_submitted>July 4, 2022</last_update_submitted>
  <last_update_submitted_qc>July 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Columbia University</investigator_affiliation>
    <investigator_full_name>Jeanine D'Armiento</investigator_full_name>
    <investigator_title>Associate Professor of Medicine (in Anesthesiology)</investigator_title>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>multi-organ failure</keyword>
  <keyword>acute kidney injury</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Angiotensin I (1-7)</mesh_term>
  </intervention_browse>
  <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>August 25, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/23/NCT04401423/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>TXA127</title>
          <description>Participants received one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
TXA127: 0.5 mg/kg per day</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Participants received one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
Placebo: 0.5 mg/kg per day</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>We included in our analysis participants whom completed minimum of 1 day of drug/placebo.</population>
      <group_list>
        <group group_id="B1">
          <title>TXA127</title>
          <description>Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
TXA127: 0.5 mg/kg per day</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
Placebo: 0.5 mg/kg per day</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="11"/>
            <count group_id="B2" value="9"/>
            <count group_id="B3" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55" lower_limit="41" upper_limit="79"/>
                    <measurement group_id="B2" value="55" lower_limit="28" upper_limit="83"/>
                    <measurement group_id="B3" value="55" lower_limit="28" upper_limit="83"/>
                  </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="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_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="11"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Oxygen at randomization</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Room air</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal cannula</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>High flow nasal cannula</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-invasive ventilation/BiPAP</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change of Serum Creatinine</title>
        <description>Calculated from baseline (at enrollment) to end of study</description>
        <time_frame>Day 1 and Day 10</time_frame>
        <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis - which is not the same as those who &quot;completed&quot; the study as seen under Participant Flow. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</population>
        <group_list>
          <group group_id="O1">
            <title>TXA127</title>
            <description>Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
TXA127: 0.5 mg/kg per day</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
Placebo: 0.5 mg/kg per day</description>
          </group>
        </group_list>
        <measure>
          <title>Change of Serum Creatinine</title>
          <description>Calculated from baseline (at enrollment) to end of study</description>
          <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis - which is not the same as those who &quot;completed&quot; the study as seen under Participant Flow. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</population>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.92" lower_limit="0.56" upper_limit="1.26"/>
                    <measurement group_id="O2" value="0.70" lower_limit="0.45" upper_limit="1.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Requiring Intubation</title>
        <time_frame>From Day 1 to Day 10</time_frame>
        <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</population>
        <group_list>
          <group group_id="O1">
            <title>TXA127</title>
            <description>Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
TXA127: 0.5 mg/kg per day</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
Placebo: 0.5 mg/kg per day</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Requiring Intubation</title>
          <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</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="11"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Requiring Dialysis</title>
        <time_frame>Up to Day 10</time_frame>
        <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</population>
        <group_list>
          <group group_id="O1">
            <title>TXA127</title>
            <description>Participants received one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
TXA127: 0.5 mg/kg per day</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
Placebo: 0.5 mg/kg per day</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Requiring Dialysis</title>
          <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</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="11"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Requiring a Vasopressors</title>
        <time_frame>Up to Day 10</time_frame>
        <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</population>
        <group_list>
          <group group_id="O1">
            <title>TXA127</title>
            <description>Participants received one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
TXA127: 0.5 mg/kg per day</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
Placebo: 0.5 mg/kg per day</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Requiring a Vasopressors</title>
          <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</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="11"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in Supplemental Oxygen Requirements</title>
        <time_frame>Day 1 and Day 10</time_frame>
        <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</population>
        <group_list>
          <group group_id="O1">
            <title>TXA127</title>
            <description>Participants received one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
TXA127: 0.5 mg/kg per day</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
Placebo: 0.5 mg/kg per day</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in Supplemental Oxygen Requirements</title>
          <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</population>
          <units>percent change of oxygen</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.71" lower_limit="-5.0" upper_limit="5.38"/>
                    <measurement group_id="O2" value="0.91" lower_limit="-5.05" upper_limit="5.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Days of Hospital Stay and Drug Administration</title>
        <time_frame>Day 1 to Day 10</time_frame>
        <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</population>
        <group_list>
          <group group_id="O1">
            <title>TXA127</title>
            <description>Participants received one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
TXA127: 0.5 mg/kg per day</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
Placebo: 0.5 mg/kg per day</description>
          </group>
        </group_list>
        <measure>
          <title>Days of Hospital Stay and Drug Administration</title>
          <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Length of Hospital Stay</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11" lower_limit="6" upper_limit="21"/>
                    <measurement group_id="O2" value="7" lower_limit="6" upper_limit="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Days of Drug/placebo administration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="2.5" upper_limit="8.5"/>
                    <measurement group_id="O2" value="5" lower_limit="4" upper_limit="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine Levels on the Day of Drug/TXA Administration</title>
        <time_frame>Day 1</time_frame>
        <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</population>
        <group_list>
          <group group_id="O1">
            <title>TXA127</title>
            <description>Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
TXA127: 0.5 mg/kg per day</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
Placebo: 0.5 mg/kg per day</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine Levels on the Day of Drug/TXA Administration</title>
          <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</population>
          <units>pg/ml</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Interferon-γ</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.44" lower_limit="0.64" upper_limit="2.24"/>
                    <measurement group_id="O2" value="1.0" lower_limit="0.59" upper_limit="1.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-1β</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.7" lower_limit="11.7" upper_limit="41.9"/>
                    <measurement group_id="O2" value="30.6" lower_limit="10.9" upper_limit="75.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-1Ra</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.9" lower_limit="8.73" upper_limit="17.21"/>
                    <measurement group_id="O2" value="7.6" lower_limit="4.48" upper_limit="19.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.52" lower_limit="0.19" upper_limit="1.17"/>
                    <measurement group_id="O2" value="0.37" lower_limit="0.16" upper_limit="0.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.41" lower_limit="0.21" upper_limit="0.78"/>
                    <measurement group_id="O2" value="0.21" lower_limit="0.05" upper_limit="1.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.72" lower_limit="1.02" upper_limit="8.20"/>
                    <measurement group_id="O2" value="1.21" lower_limit="0.90" upper_limit="1.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.63" lower_limit="5.58" upper_limit="51.79"/>
                    <measurement group_id="O2" value="3.35" lower_limit="2.79" upper_limit="9.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.4" lower_limit="15.9" upper_limit="61.1"/>
                    <measurement group_id="O2" value="16.2" lower_limit="10.3" upper_limit="23.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TNF-α</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.4" lower_limit="30.9" upper_limit="95.9"/>
                    <measurement group_id="O2" value="45.9" lower_limit="37.16" upper_limit="58.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.3" lower_limit="5.4" upper_limit="29.6"/>
                    <measurement group_id="O2" value="10.8" lower_limit="1.35" upper_limit="25.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-12p40</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.4" lower_limit="24.5" upper_limit="64.2"/>
                    <measurement group_id="O2" value="28.9" lower_limit="18.1" upper_limit="45.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-12p70</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.74" lower_limit="0.83" upper_limit="2.74"/>
                    <measurement group_id="O2" value="0.63" lower_limit="0.30" upper_limit="1.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-13</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.9" lower_limit="8.11" upper_limit="43.5"/>
                    <measurement group_id="O2" value="8.5" lower_limit="6.49" upper_limit="14.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MCP-1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="345" lower_limit="248" upper_limit="479"/>
                    <measurement group_id="O2" value="283" lower_limit="219" upper_limit="351"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cytokine Levels on the Day 5 of Drug/TXA Administration</title>
        <time_frame>Day 5</time_frame>
        <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</population>
        <group_list>
          <group group_id="O1">
            <title>TXA127</title>
            <description>Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
TXA127: 0.5 mg/kg per day</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
Placebo: 0.5 mg/kg per day</description>
          </group>
        </group_list>
        <measure>
          <title>Cytokine Levels on the Day 5 of Drug/TXA Administration</title>
          <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</population>
          <units>pg/ml</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Interferon-γ</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.88" lower_limit="0.59" upper_limit="1.63"/>
                    <measurement group_id="O2" value="0.78" lower_limit="0.58" upper_limit="1.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-1β</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.4" lower_limit="6.1" upper_limit="27.0"/>
                    <measurement group_id="O2" value="50.6" lower_limit="29.7" upper_limit="71.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-1Ra</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.77" lower_limit="7.92" upper_limit="28.43"/>
                    <measurement group_id="O2" value="7.38" lower_limit="4.18" upper_limit="16.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.20" lower_limit="0.12" upper_limit="0.48"/>
                    <measurement group_id="O2" value="0.91" lower_limit="0.83" upper_limit="4.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.09" lower_limit="0.05" upper_limit="0.30"/>
                    <measurement group_id="O2" value="0.74" lower_limit="0.44" upper_limit="1.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.36" lower_limit="2.34" upper_limit="11.74"/>
                    <measurement group_id="O2" value="0.99" lower_limit="0.77" upper_limit="2.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.88" lower_limit="5.03" upper_limit="33.21"/>
                    <measurement group_id="O2" value="1.34" lower_limit="0.78" upper_limit="6.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.5" lower_limit="14.1" upper_limit="29.3"/>
                    <measurement group_id="O2" value="14.3" lower_limit="6.5" upper_limit="56.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TNF-α</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.1" lower_limit="27.3" upper_limit="61.8"/>
                    <measurement group_id="O2" value="42.1" lower_limit="36.2" upper_limit="60.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.46" lower_limit="2.03" upper_limit="2.75"/>
                    <measurement group_id="O2" value="4.19" lower_limit="1.65" upper_limit="6.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-12p40</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.40" lower_limit="31.7" upper_limit="55.9"/>
                    <measurement group_id="O2" value="29.8" lower_limit="22.1" upper_limit="38.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-12p70</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.28" lower_limit="0.42" upper_limit="1.64"/>
                    <measurement group_id="O2" value="1.21" lower_limit="0.89" upper_limit="1.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-13</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.71" lower_limit="8.11" upper_limit="25.01"/>
                    <measurement group_id="O2" value="11.4" lower_limit="11.1" upper_limit="13.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MCP-1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="218" lower_limit="191" upper_limit="317"/>
                    <measurement group_id="O2" value="237" lower_limit="179" upper_limit="264"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mortality</title>
        <time_frame>Day 1 to Day 10</time_frame>
        <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</population>
        <group_list>
          <group group_id="O1">
            <title>TXA127</title>
            <description>Participants received one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
TXA127: 0.5 mg/kg per day</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
Placebo: 0.5 mg/kg per day</description>
          </group>
        </group_list>
        <measure>
          <title>Mortality</title>
          <population>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</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="11"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected from Day 1 to Day 10 of study drug/placebo administration (or as long as hospitalized if less than 10 days) and at Day 28 and Day 60 (post hospital discharge) during a follow-up phone call.</time_frame>
      <desc>Only subjects who received at least 1 complete dose of drug/placebo were included in the data analysis - which is not the same as those who &quot;completed&quot; the study as seen under Participant Flow. This included 11 out of 11 in the TXA127 group and 9 out of 11 in the Placebo group.</desc>
      <group_list>
        <group group_id="E1">
          <title>TXA127</title>
          <description>Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
TXA127: 0.5 mg/kg per day</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).&#xD;
Placebo: 0.5 mg/kg per day</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-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="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Intubation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="11"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="7" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Right abdominal side pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Hematochezia</sub_title>
                <description>Blood in stool</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Diaphoresis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Cloudiness of Consciousness</sub_title>
                <description>Brain fog</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Transient Paresthesia</sub_title>
                <description>Numbness in left leg</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Refractory Hypoxemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Tussis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Angina Pectoris</sub_title>
                <description>Chest Tightness</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dyshidrotic Dermatitis</sub_title>
                <description>Itchy hands and feet</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Refractory Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </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. Jeanine D'Armiento / Principal Investigator</name_or_title>
      <organization>Columbia University Irving Medical Center</organization>
      <phone>212-305-3745</phone>
      <email>jmd12@cumc.columbia.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/NCT04401423
org study id: AAAT0535
nct id: NCT04401423
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to determine if administration of angiotensin-(1-7) (TXA127)
      prevents acute kidney injury and deterioration into multi-organ failure in patients with
      severe COVID-19. Participants will undergo a 10-day treatment with either placebo or study
      drug. The drug will be administered intravenously for 3 hours once each day for 10 days
      consecutively.
Corona virus disease 2019 (COVID-19) has been associated with severe respiratory and
      multiorgan failure. Research shows that COVID-19 reduces levels of angiotensin-converting
      enzyme-2 (ACE-2), an enzyme that converts angiotensin II to angiotensin 1-7 (known as
      TXA127). COVID-19 reduces levels of ACE-2 and therefore angiotensin 1-7 and as a result,
      angiotensin II levels are going to be increased. Many clinical observations in COVID-19 have
      shown the high incidence of acute kidney injury that may be due to excessive levels of
      angiotensin II. The investigators hypothesize that administration of angiotensin (1-7)
      replaces levels of ACE-2 in COVID-19 and thereby ameliorates deterioration of multi-organ
      failure and specifically acute kidney injury.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Double-blinded, placebo-control, randomized clinical trial
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change of Serum Creatinine
time frame: Day 1 and Day 10
description: Calculated from baseline (at enrollment) to end of study
measure: Number of Participants Requiring Intubation
time frame: From Day 1 to Day 10
measure: Number of Participants Requiring Dialysis
time frame: Up to Day 10
measure: Number of Participants Requiring a Vasopressors
time frame: Up to Day 10
measure: Percent Change in Supplemental Oxygen Requirements
time frame: Day 1 and Day 10
measure: Days of Hospital Stay and Drug Administration
time frame: Day 1 to Day 10
measure: Cytokine Levels on the Day of Drug/TXA Administration
time frame: Day 1
measure: Cytokine Levels on the Day 5 of Drug/TXA Administration
time frame: Day 5
measure: Mortality
time frame: Day 1 to Day 10
arm group label: TXA127
arm group type: Experimental
description: Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will receive one 3-hour dosage (0.5 mg/kg per day), intravenously, for 10 days consecutively (or until discharge if less than 10 days).
intervention type: Drug
intervention name: TXA127
description: 0.5 mg/kg per day
arm group label: TXA127
other name: angiotensin-(1-7)
intervention type: Drug
intervention name: Placebo
description: 0.5 mg/kg per day
arm group label: Placebo
other name: control
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jeanine D'Armiento, MD, PhD
role: Principal Investigator
affiliation: Associate Professor of Medicine in Anesthesiology
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Columbia University
investigator full name: Jeanine D'Armiento
investigator title: Associate Professor of Medicine (in Anesthesiology)
mesh term: COVID-19
mesh term: Angiotensin I (1-7)
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 