<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/NCT04505592</url>
  </required_header>
  <id_info>
    <org_study_id>GCO 20-1764</org_study_id>
    <nct_id>NCT04505592</nct_id>
  </id_info>
  <brief_title>Tenecteplase in Patients With COVID-19</brief_title>
  <official_title>Tenecteplase With Concomitant Anticoagulation for Severe Acute Respiratory Failure in Patients With COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hooman Poor</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Icahn School of Medicine at Mount Sinai</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 placebo-controlled, double blind, randomized, Phase II dose escalation study&#xD;
      intended to evaluate the potential safety and efficacy of tenecteplase for the treatment of&#xD;
      COVID-19 associated respiratory failure. The hypothesis is that administration of the drug,&#xD;
      in conjunction with heparin anticoagulation, will improve patients' clinical outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with COVID-19 who suffer from acute hypoxemic respiratory failure have a poor&#xD;
      prognosis. COVID-19 has been associated with a hyperinflammatory and hypercoagulable state,&#xD;
      leading to a range of thromboembolic complications from pulmonary embolism to ischemic&#xD;
      stroke. Furthermore, emerging data suggest that the associated acute respiratory failure is,&#xD;
      at least in part, due to pulmonary vascular disease caused by micro- and/or macro-emboli,&#xD;
      creating pulmonary vascular shunting and dead-space ventilation. In this placebo-controlled,&#xD;
      double blind, randomized, Phase II dose escalation study, we plan to evaluate the clinical&#xD;
      efficacy and safety of low-dose IV bolus tenecteplase together with anticoagulation compared&#xD;
      with control patients on therapeutic anticoagulation alone in hospitalized adults diagnosed&#xD;
      with COVID-19 respiratory failure with elevated D-dimer. We believe these patients can be&#xD;
      successfully treated without significantly increasing the risk of major bleeding while&#xD;
      improving recovery rates, shorten hospitalization time, and perhaps ultimately prove to&#xD;
      improve survival.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 25, 2020</start_date>
  <completion_date type="Actual">March 10, 2022</completion_date>
  <primary_completion_date type="Actual">March 10, 2022</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>Sequential Assignment</intervention_model>
    <intervention_model_description>Subjects will be randomized in a 2:1 ratio to treatment or control in blocks of 15, performed twice per dose (low and high) with randomization stratified by site.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Patients and study investigators will be blinded to subject treatment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Free of Respiratory Failure</measure>
    <time_frame>28 Days</time_frame>
    <description>The number of patients free of respiratory failure defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation at 28 days</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Occurrences of Bleeding</measure>
    <time_frame>28 days</time_frame>
    <description>Safety as assessed by number of participants with occurrences of intracranial bleeding or major bleeding</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With In-hospital Deaths at 14 Days</measure>
    <time_frame>14 days</time_frame>
    <description>Number of patients who expired in the hospital within the first 14 days of their participation in the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Death at 28 Days</measure>
    <time_frame>28 days</time_frame>
    <description>Number of participants who expired by 28 days/end of study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Ventilator-free Days</measure>
    <time_frame>28 days</time_frame>
    <description>Number of ventilator-free days in 28 days period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Respiratory Failure-free Days</measure>
    <time_frame>28 days</time_frame>
    <description>Respiratory failure-free defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation. Number of respiratory failure-free days in 28 days period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Vasopressor-free Days</measure>
    <time_frame>28 days</time_frame>
    <description>Number of vasopressor-free days over 28 days period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Vasopressor Doses at 24 Hours</measure>
    <time_frame>24 hours and 72 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>P/F Ratio</measure>
    <time_frame>24 hours and 72 hours</time_frame>
    <description>The P/F ratio equals the arterial pO2 (&quot;P&quot;) from the ABG divided by the FIO2 (&quot;F&quot;) - the fraction (percent) of inspired oxygen that the patient is receiving expressed as a decimal (40% oxygen = FIO2 of 0.40).&#xD;
Ratio of arterial pO2 over fraction of inspired oxygen that the person is receiving.&#xD;
Normal P/F Ratio is ≥ 400.&#xD;
300 to 200 is considered mild ARDS&#xD;
200 to 100 is considered moderate ARDS&#xD;
Anything below 100 is considered severe ARDS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of ICU-free Days</measure>
    <time_frame>28 days</time_frame>
    <description>Number of days the patient spent outside the ICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Length of Stay</measure>
    <time_frame>up to 29 days</time_frame>
    <description>Length of time the patient spent in the hospital, including ICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With New-onset Renal Failure</measure>
    <time_frame>28 days</time_frame>
    <description>Number of patients who experienced renal failure during the course of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Need for Renal Replacement Therapy</measure>
    <time_frame>28 days</time_frame>
    <description>Number of patients who underwent renal replacement treatment for their renal failure</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>COVID-19</condition>
  <condition>Respiratory Failure</condition>
  <condition>ARDS</condition>
  <arm_group>
    <arm_group_label>Tenecteplase</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>First 20 patients randomized to treatment will receive tenecteplase 0.25 mg/kg (maximum 25 mg). Last 20 patients randomized to treatment will receive tenecteplase 0.50 mg/kg (maximum 40 mg).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo control</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenecteplase</intervention_name>
    <description>First 20 patients randomized to treatment arm will receive 0.25 mg/kg of tenecteplase. Next 20 patients randomized to treatment arm will receive 0.50 mg/kg of tenecteplase. Both will receive concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
    <arm_group_label>Tenecteplase</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Patients will receive placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Patient/legally authorized representative has completed the Informed Consent Form&#xD;
&#xD;
          -  Age ≥18 years&#xD;
&#xD;
          -  Ability to comply with the study protocol, in the investigator's judgment&#xD;
&#xD;
          -  Respiratory failure secondary to COVID-19 requiring mechanical ventilation for no&#xD;
             greater than 24 hours, or high-flow nasal cannula (HFNC),non-rebreather (NRB) mask or&#xD;
             non-invasive positive pressure ventilation (NIPPV) for no greater than 48 hours&#xD;
&#xD;
          -  Confirmed infection with SARS-CoV-2 virus (PCR positive within 14 days)&#xD;
&#xD;
          -  Elevated D-dimer (&gt;6 times upper limit of normal within past 72 hours)&#xD;
&#xD;
          -  For patient who are intubated &gt;12 hours prior to randomization or with any evidence of&#xD;
             neurologic deficit a head CT within 12 hours demonstrating no evidence of acute or&#xD;
             subacute infarct or hemorrhage&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Current participation in another investigational drug study within the prior 7 days&#xD;
&#xD;
          -  Known hypersensitivity or allergy to any ingredients of tenecteplase&#xD;
&#xD;
          -  Active internal bleeding&#xD;
&#xD;
          -  Known bleeding diathesis&#xD;
&#xD;
          -  Use of one of the new oral anticoagulants within the last 48 hours (dabigatran,&#xD;
             rivaroxaban, apixaban, edoxaban)&#xD;
&#xD;
          -  Treatment with a thrombolytic within the last 3 months prior to randomization&#xD;
             (exception for the use of Cathflo alteplase for occlusions of central venous&#xD;
             catheters)&#xD;
&#xD;
          -  Baseline platelet count &lt;80,000/L (results must be available prior to treatment)&#xD;
&#xD;
          -  Baseline blood glucose &gt;400 mg/dL (22.20 mmol/L)&#xD;
&#xD;
          -  Baseline blood glucose &lt;50 mg/dL needs to be normalized prior to randomization&#xD;
&#xD;
          -  Intracranial or intraspinal surgery or trauma within 2 months&#xD;
&#xD;
          -  Other, non-COVID-19 related, serious, advanced, or terminal illness (investigator&#xD;
             judgment) or life expectancy is less than 6 months&#xD;
&#xD;
          -  History of acute ischemic stroke in the last 90 days&#xD;
&#xD;
          -  History of intracranial bleeding, including hemorrhagic stroke&#xD;
&#xD;
          -  Presumed septic embolus; suspicion of bacterial endocarditis&#xD;
&#xD;
          -  Mechanical ventilation &gt; 24 hours, HFNC, NRB, NIPPV, or any combination, for greater&#xD;
             than 48 hours&#xD;
&#xD;
          -  Mechanical ventilation, HFNC, NRB, or NIPVV (for reasons other than obstructive sleep&#xD;
             apnea) within the prior 30 days (excluding 48 hours prior to randomization)&#xD;
&#xD;
          -  Moribund status suggesting imminent vascular collapse and inability to survive &gt; 72&#xD;
             hours (investigator determination)&#xD;
&#xD;
          -  Uncontrolled hypertension defined as systolic BP &gt; 180 mm Hg and/or diastolic BP &gt; 110&#xD;
             mm Hgb&#xD;
&#xD;
          -  Age &gt; 75 years&#xD;
&#xD;
          -  History of traumatic brain injury within 2 months&#xD;
&#xD;
          -  Recent head trauma with fracture or brain injury&#xD;
&#xD;
          -  History of Heparin Induced Thrombocytopenia (HIT) and/or other hereditary or acquired&#xD;
             hemorrhagic diathesis or coagulation factor deficiency&#xD;
&#xD;
          -  INR &gt; 2 or recent oral anticoagulant therapy with INR &gt;1.7&#xD;
&#xD;
          -  Pregnancy or lactation within the prior 30 days; women of childbearing age (&lt;55 years&#xD;
             old) should have documentation of a negative pregnancy test&#xD;
&#xD;
          -  Chronic liver disease defined as &gt; Childs-Pugh Class B&#xD;
&#xD;
          -  Atrial fibrillation, mitral stenosis, or known left heart thrombosis&#xD;
&#xD;
          -  Any other condition that, in the opinion of the investigator, precludes administration&#xD;
             of tenecteplase or poses a significant hazard to the patient receives tenecteplase&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hooman Poor, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Icahn School of Medicine at Mount Sinai</affiliation>
  </overall_official>
  <overall_official>
    <last_name>J Mocco, MD</last_name>
    <role>Study Director</role>
    <affiliation>Icahn School of Medicine at Mount Sinai</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</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>August 6, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <results_first_submitted>March 8, 2023</results_first_submitted>
  <results_first_submitted_qc>April 4, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">April 6, 2023</results_first_posted>
  <last_update_submitted>April 4, 2023</last_update_submitted>
  <last_update_submitted_qc>April 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Icahn School of Medicine at Mount Sinai</investigator_affiliation>
    <investigator_full_name>Hooman Poor</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>ARDS</keyword>
  <keyword>thrombolysis</keyword>
  <keyword>tenecteplase</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Respiratory Insufficiency</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenecteplase</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>June 15, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT04505592/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Patients were recruited in a tertiary academic hospital in New York City.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Tenecteplase</title>
          <description>Tenecteplase 0.25 mg/kg (maximum dose of 25 mg) And received concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Patients received placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</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>
      <group_list>
        <group group_id="B1">
          <title>Tenecteplase</title>
          <description>Tenecteplase 0.25 mg/kg (maximum dose of 25 mg) And received concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Patients received placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</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="8"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="13"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="67.5" lower_limit="55" upper_limit="71"/>
                    <measurement group_id="B2" value="71" lower_limit="52" upper_limit="73"/>
                    <measurement group_id="B3" value="69" lower_limit="52" upper_limit="73"/>
                  </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="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="9"/>
                  </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="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="11"/>
                  </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>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="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</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>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <units>kg/m^2</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="35" lower_limit="31" upper_limit="39"/>
                    <measurement group_id="B2" value="26" lower_limit="24" upper_limit="27"/>
                    <measurement group_id="B3" value="31" lower_limit="26" upper_limit="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hypertension</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diabetes</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Coronary Artery Disease (CAD)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Obstructive Sleep Apnea</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <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>
          <title>Respiratory Support</title>
          <description>Participants can have more than 1 type of respiratory support at baseline</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Mechanical ventilation</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>
              <title>high-flow nasal cannula (HFNC)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>non-rebreather (NRB)</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>
              <title>non-invasive positive pressure ventilation (NIPPV)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Steroids</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Remdesivir</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>P/F Ratio</title>
          <description>Ratio of arterial pO2 over fraction of inspired oxygen that the patient is receiving. Normal P/F Ratio is ≥ 400.&#xD;
300 to 200 is considered mild ARDS&#xD;
200 to 100 is considered moderate ARDS&#xD;
Anything below 100 is considered severe ARDS.</description>
          <units>Ratio</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="80" lower_limit="67" upper_limit="111"/>
                    <measurement group_id="B2" value="87" lower_limit="72" upper_limit="131"/>
                    <measurement group_id="B3" value="83" lower_limit="68" upper_limit="119"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Free of Respiratory Failure</title>
        <description>The number of patients free of respiratory failure defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation at 28 days</description>
        <time_frame>28 Days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tenecteplase</title>
            <description>Tenecteplase 0.25 mg/kg (maximum dose of 25 mg) And received concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients received placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Free of Respiratory Failure</title>
          <description>The number of patients free of respiratory failure defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation at 28 days</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Occurrences of Bleeding</title>
        <description>Safety as assessed by number of participants with occurrences of intracranial bleeding or major bleeding</description>
        <time_frame>28 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tenecteplase</title>
            <description>Tenecteplase 0.25 mg/kg (maximum dose of 25 mg) And received concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients received placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Occurrences of Bleeding</title>
          <description>Safety as assessed by number of participants with occurrences of intracranial bleeding or major bleeding</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With In-hospital Deaths at 14 Days</title>
        <description>Number of patients who expired in the hospital within the first 14 days of their participation in the study</description>
        <time_frame>14 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tenecteplase</title>
            <description>Tenecteplase 0.25 mg/kg (maximum dose of 25 mg) And received concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients received placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With In-hospital Deaths at 14 Days</title>
          <description>Number of patients who expired in the hospital within the first 14 days of their participation in the study</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Death at 28 Days</title>
        <description>Number of participants who expired by 28 days/end of study</description>
        <time_frame>28 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tenecteplase</title>
            <description>Tenecteplase 0.25 mg/kg (maximum dose of 25 mg) And received concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients received placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Death at 28 Days</title>
          <description>Number of participants who expired by 28 days/end of study</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Ventilator-free Days</title>
        <description>Number of ventilator-free days in 28 days period</description>
        <time_frame>28 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tenecteplase</title>
            <description>Tenecteplase 0.25 mg/kg (maximum dose of 25 mg) And received concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients received placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Ventilator-free Days</title>
          <description>Number of ventilator-free days in 28 days period</description>
          <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="8"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18" lower_limit="3" upper_limit="28"/>
                    <measurement group_id="O2" value="19" lower_limit="9" upper_limit="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Respiratory Failure-free Days</title>
        <description>Respiratory failure-free defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation. Number of respiratory failure-free days in 28 days period.</description>
        <time_frame>28 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tenecteplase</title>
            <description>Tenecteplase 0.25 mg/kg (maximum dose of 25 mg) And received concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients received placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Respiratory Failure-free Days</title>
          <description>Respiratory failure-free defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation. Number of respiratory failure-free days in 28 days period.</description>
          <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="8"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5" lower_limit="0" upper_limit="3"/>
                    <measurement group_id="O2" value="3" lower_limit="1" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Vasopressor-free Days</title>
        <description>Number of vasopressor-free days over 28 days period</description>
        <time_frame>28 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tenecteplase</title>
            <description>Tenecteplase 0.25 mg/kg (maximum dose of 25 mg) And received concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients received placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Vasopressor-free Days</title>
          <description>Number of vasopressor-free days over 28 days period</description>
          <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="8"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9" lower_limit="4.6" upper_limit="18.5"/>
                    <measurement group_id="O2" value="9" lower_limit="9" upper_limit="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Vasopressor Doses at 24 Hours</title>
        <time_frame>24 hours and 72 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tenecteplase</title>
            <description>Tenecteplase 0.25 mg/kg (maximum dose of 25 mg) And received concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients received placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Vasopressor Doses at 24 Hours</title>
          <units>doses</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours</title>
              <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>P/F Ratio</title>
        <description>The P/F ratio equals the arterial pO2 (&quot;P&quot;) from the ABG divided by the FIO2 (&quot;F&quot;) - the fraction (percent) of inspired oxygen that the patient is receiving expressed as a decimal (40% oxygen = FIO2 of 0.40).&#xD;
Ratio of arterial pO2 over fraction of inspired oxygen that the person is receiving.&#xD;
Normal P/F Ratio is ≥ 400.&#xD;
300 to 200 is considered mild ARDS&#xD;
200 to 100 is considered moderate ARDS&#xD;
Anything below 100 is considered severe ARDS.</description>
        <time_frame>24 hours and 72 hours</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tenecteplase</title>
            <description>Tenecteplase 0.25 mg/kg (maximum dose of 25 mg) And received concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients received placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
        </group_list>
        <measure>
          <title>P/F Ratio</title>
          <description>The P/F ratio equals the arterial pO2 (&quot;P&quot;) from the ABG divided by the FIO2 (&quot;F&quot;) - the fraction (percent) of inspired oxygen that the patient is receiving expressed as a decimal (40% oxygen = FIO2 of 0.40).&#xD;
Ratio of arterial pO2 over fraction of inspired oxygen that the person is receiving.&#xD;
Normal P/F Ratio is ≥ 400.&#xD;
300 to 200 is considered mild ARDS&#xD;
200 to 100 is considered moderate ARDS&#xD;
Anything below 100 is considered severe ARDS.</description>
          <units>Ratio</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="8"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>24 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="89" lower_limit="68" upper_limit="92"/>
                    <measurement group_id="O2" value="97" lower_limit="89" upper_limit="146"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>72 hours</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="89" lower_limit="63" upper_limit="91"/>
                    <measurement group_id="O2" value="78" lower_limit="77" upper_limit="137"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of ICU-free Days</title>
        <description>Number of days the patient spent outside the ICU</description>
        <time_frame>28 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tenecteplase</title>
            <description>Tenecteplase 0.25 mg/kg (maximum dose of 25 mg) And received concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients received placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of ICU-free Days</title>
          <description>Number of days the patient spent outside the ICU</description>
          <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="8"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="1" upper_limit="7"/>
                    <measurement group_id="O2" value="1" lower_limit="1" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Hospital Length of Stay</title>
        <description>Length of time the patient spent in the hospital, including ICU</description>
        <time_frame>up to 29 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tenecteplase</title>
            <description>Tenecteplase 0.25 mg/kg (maximum dose of 25 mg) And received concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients received placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
        </group_list>
        <measure>
          <title>Hospital Length of Stay</title>
          <description>Length of time the patient spent in the hospital, including ICU</description>
          <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="8"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11" lower_limit="7.8" upper_limit="29"/>
                    <measurement group_id="O2" value="13" lower_limit="12" upper_limit="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With New-onset Renal Failure</title>
        <description>Number of patients who experienced renal failure during the course of the study</description>
        <time_frame>28 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tenecteplase</title>
            <description>Tenecteplase 0.25 mg/kg (maximum dose of 25 mg) And received concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients received placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With New-onset Renal Failure</title>
          <description>Number of patients who experienced renal failure during the course of the study</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Need for Renal Replacement Therapy</title>
        <description>Number of patients who underwent renal replacement treatment for their renal failure</description>
        <time_frame>28 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Tenecteplase</title>
            <description>Tenecteplase 0.25 mg/kg (maximum dose of 25 mg) And received concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients received placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Need for Renal Replacement Therapy</title>
          <description>Number of patients who underwent renal replacement treatment for their renal failure</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>28 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Tenecteplase</title>
          <description>Tenecteplase 0.25 mg/kg (maximum dose of 25 mg) And received concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Patients received placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (Unspecified)</default_vocab>
        <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="2" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Large retroperitoneal hematoma with hgb drop</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Hemorrhagic shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Compartment syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiogenic shock</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>ST Elevation Myocardial Infarction (STEMI)</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Worsening respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Intubation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (Unspecified)</default_vocab>
        <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="3" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased hemoglobin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Mild oral bleeding</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Bleeding from mouth and wrist</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="5"/>
              </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. Hooman Poor</name_or_title>
      <organization>Icahn School of Medicine at Mount Sinai</organization>
      <phone>(212) 241-5656</phone>
      <email>hooman.poor@mountsinai.org</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/NCT04505592
org study id: GCO 20-1764
nct id: NCT04505592
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a placebo-controlled, double blind, randomized, Phase II dose escalation study
      intended to evaluate the potential safety and efficacy of tenecteplase for the treatment of
      COVID-19 associated respiratory failure. The hypothesis is that administration of the drug,
      in conjunction with heparin anticoagulation, will improve patients' clinical outcomes.
Patients with COVID-19 who suffer from acute hypoxemic respiratory failure have a poor
      prognosis. COVID-19 has been associated with a hyperinflammatory and hypercoagulable state,
      leading to a range of thromboembolic complications from pulmonary embolism to ischemic
      stroke. Furthermore, emerging data suggest that the associated acute respiratory failure is,
      at least in part, due to pulmonary vascular disease caused by micro- and/or macro-emboli,
      creating pulmonary vascular shunting and dead-space ventilation. In this placebo-controlled,
      double blind, randomized, Phase II dose escalation study, we plan to evaluate the clinical
      efficacy and safety of low-dose IV bolus tenecteplase together with anticoagulation compared
      with control patients on therapeutic anticoagulation alone in hospitalized adults diagnosed
      with COVID-19 respiratory failure with elevated D-dimer. We believe these patients can be
      successfully treated without significantly increasing the risk of major bleeding while
      improving recovery rates, shorten hospitalization time, and perhaps ultimately prove to
      improve survival.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: Subjects will be randomized in a 2:1 ratio to treatment or control in blocks of 15, performed twice per dose (low and high) with randomization stratified by site.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Patients and study investigators will be blinded to subject treatment.
measure: Number of Participants Free of Respiratory Failure
time frame: 28 Days
description: The number of patients free of respiratory failure defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation at 28 days
measure: Number of Participants With Occurrences of Bleeding
time frame: 28 days
description: Safety as assessed by number of participants with occurrences of intracranial bleeding or major bleeding
measure: Number of Participants With In-hospital Deaths at 14 Days
time frame: 14 days
description: Number of patients who expired in the hospital within the first 14 days of their participation in the study
measure: Number of Participants With Death at 28 Days
time frame: 28 days
description: Number of participants who expired by 28 days/end of study
measure: Number of Ventilator-free Days
time frame: 28 days
description: Number of ventilator-free days in 28 days period
measure: Number of Respiratory Failure-free Days
time frame: 28 days
description: Respiratory failure-free defined as not requiring high flow nasal cannula, non-rebreather, noninvasive positive pressure ventilation, or mechanical ventilation. Number of respiratory failure-free days in 28 days period.
measure: Number of Vasopressor-free Days
time frame: 28 days
description: Number of vasopressor-free days over 28 days period
measure: Number of Vasopressor Doses at 24 Hours
time frame: 24 hours and 72 hours
measure: P/F Ratio
time frame: 24 hours and 72 hours
description: The P/F ratio equals the arterial pO2 ("P") from the ABG divided by the FIO2 ("F") - the fraction (percent) of inspired oxygen that the patient is receiving expressed as a decimal (40% oxygen = FIO2 of 0.40).
Ratio of arterial pO2 over fraction of inspired oxygen that the person is receiving.
Normal P/F Ratio is ≥ 400.
300 to 200 is considered mild ARDS
200 to 100 is considered moderate ARDS
Anything below 100 is considered severe ARDS.
measure: Number of ICU-free Days
time frame: 28 days
description: Number of days the patient spent outside the ICU
measure: Hospital Length of Stay
time frame: up to 29 days
description: Length of time the patient spent in the hospital, including ICU
measure: Number of Participants With New-onset Renal Failure
time frame: 28 days
description: Number of patients who experienced renal failure during the course of the study
measure: Number of Participants With Need for Renal Replacement Therapy
time frame: 28 days
description: Number of patients who underwent renal replacement treatment for their renal failure
arm group label: Tenecteplase
arm group type: Experimental
description: First 20 patients randomized to treatment will receive tenecteplase 0.25 mg/kg (maximum 25 mg). Last 20 patients randomized to treatment will receive tenecteplase 0.50 mg/kg (maximum 40 mg).
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo control
intervention type: Drug
intervention name: Tenecteplase
description: First 20 patients randomized to treatment arm will receive 0.25 mg/kg of tenecteplase. Next 20 patients randomized to treatment arm will receive 0.50 mg/kg of tenecteplase. Both will receive concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.
arm group label: Tenecteplase
intervention type: Drug
intervention name: Placebo
description: Patients will receive placebo with concomitant heparin to maintain activated partial thromboplastin time between 2.0 and 2.5 upper limit of normal.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Hooman Poor, MD
role: Principal Investigator
affiliation: Icahn School of Medicine at Mount Sinai
last name: J Mocco, MD
role: Study Director
affiliation: Icahn School of Medicine at Mount Sinai
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Icahn School of Medicine at Mount Sinai
investigator full name: Hooman Poor
investigator title: Assistant Professor of Medicine
mesh term: COVID-19
mesh term: Respiratory Insufficiency
mesh term: Tenecteplase
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 