<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/NCT04409834</url>
  </required_header>
  <id_info>
    <org_study_id>CCCTN/TIMI COVID-PACT</org_study_id>
    <nct_id>NCT04409834</nct_id>
  </id_info>
  <brief_title>Prevention of Arteriovenous Thrombotic Events in Critically-Ill COVID-19 Patients Trial</brief_title>
  <acronym>COVID-PACT</acronym>
  <official_title>A Multicenter, Randomized-Controlled Trial to Evaluate the Efficacy and Safety of Antithrombotic Therapy for Prevention of Arterial and Venous Thrombotic Complications in Critically-Ill COVID-19 Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The TIMI Study Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The TIMI Study Group</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>
      This is a multicenter, open-label, 2x2 factorial, randomized-controlled trial in&#xD;
      critically-ill patients with novel coronavirus disease 2019 (COVID-19) evaluating the&#xD;
      efficacy and safety of full-dose vs. standard prophylactic dose anticoagulation and of&#xD;
      antiplatelet vs. no antiplatelet therapy for prevention of venous and arterial thrombotic&#xD;
      events.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 5, 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 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Factorial Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary endpoint: Venous or arterial thrombotic events</measure>
    <time_frame>28 days or until hospital discharge, whichever earlier</time_frame>
    <description>Hierarchical composite: Death due to venous or arterial thrombosis, pulmonary embolism, clinically evident DVT, type 1 MI, ischemic stroke, systemic embolism or acute limb ischemia, or clinically silent DVT</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Key secondary endpoint: Clinically evident venous or arterial thrombotic events</measure>
    <time_frame>28 days or until hospital discharge, whichever earlier</time_frame>
    <description>Hierarchical composite: Death due to venous or arterial thrombosis, pulmonary embolism, clinically evident DVT, type 1 MI, ischemic stroke, systemic embolism or acute limb ischemia</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">390</enrollment>
  <condition>COVID-19</condition>
  <condition>Venous Thromboembolism</condition>
  <condition>Arterial Thrombosis</condition>
  <arm_group>
    <arm_group_label>Full-dose anticoagulation + antiplatelet therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>• Full-dose anticoagulation: Unfractionated heparin IV continuous targeting aPTT of 1.5-2.5X control, or Enoxaparin 1 mg/kg SC Q12h&#xD;
• Anti-platelet therapy: Clopidogrel 300 mg PO x1, followed by clopidogrel 75 mg PO QD</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Full-dose anticoagulation + no antiplatelet therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>• Full-dose anticoagulation: Unfractionated heparin IV continuous targeting aPTT of 1.5-2.5X control, or Enoxaparin 1 mg/kg SC Q12h</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prophylactic anticoagulation + antiplatelet therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>• Standard prophylactic anticoagulation: Enoxaparin 40 mg SC QD or Unfractionated heparin 5,000 IU SC TID&#xD;
• Antiplatelet therapy: Clopidogrel 300 mg PO x1, followed by clopidogrel 75 mg PO QD</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Prophylactic anticoagulation + no antiplatelet therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>• Standard prophylactic anticoagulation: Enoxaparin 40 mg SC QD or Unfractionated heparin 5,000 IU SC TID</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Unfractionated Heparin IV</intervention_name>
    <description>Unfractionated heparin IV targeting an aPTT of 1.5-2.5 times the control</description>
    <arm_group_label>Full-dose anticoagulation + antiplatelet therapy</arm_group_label>
    <arm_group_label>Full-dose anticoagulation + no antiplatelet therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enoxaparin 1 mg/kg</intervention_name>
    <description>Enoxaparin 1 mg/kg SC Q12h</description>
    <arm_group_label>Full-dose anticoagulation + antiplatelet therapy</arm_group_label>
    <arm_group_label>Full-dose anticoagulation + no antiplatelet therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clopidogrel</intervention_name>
    <description>Clopidogrel 300 mg PO x1, then clopidogrel 75 mg PO QD</description>
    <arm_group_label>Full-dose anticoagulation + antiplatelet therapy</arm_group_label>
    <arm_group_label>Prophylactic anticoagulation + antiplatelet therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Unfractionated heparin SC</intervention_name>
    <description>Unfractionated heparin 5,000 IU SC TID</description>
    <arm_group_label>Prophylactic anticoagulation + antiplatelet therapy</arm_group_label>
    <arm_group_label>Prophylactic anticoagulation + no antiplatelet therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enoxaparin 40 Mg/0.4 mL Injectable Solution</intervention_name>
    <description>Enoxaparin 40 mg SC QD</description>
    <arm_group_label>Prophylactic anticoagulation + antiplatelet therapy</arm_group_label>
    <arm_group_label>Prophylactic anticoagulation + no antiplatelet therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥18 years (male or female)&#xD;
&#xD;
          2. Acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)&#xD;
&#xD;
          3. Currently admitted to an intensive care unit (ICU)&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. Ongoing (&gt;48 hours) or planned full-dose (therapeutic) anticoagulation for any&#xD;
             indication&#xD;
&#xD;
          2. Ongoing or planned treatment with dual antiplatelet therapy&#xD;
&#xD;
          3. Contraindication to antithrombotic therapy or high risk of bleeding due to conditions&#xD;
             including, but not limited to, any of the following:&#xD;
&#xD;
               1. History of intracranial hemorrhage, known CNS tumor or CNS vascular abnormality&#xD;
&#xD;
               2. Active or recent major bleeding within the past 30 days with untreated source&#xD;
&#xD;
               3. Platelet count &lt;70,000 or known functional platelet disorder&#xD;
&#xD;
               4. Fibrinogen &lt;200 mg/dL&#xD;
&#xD;
               5. International normalized ratio (INR) &gt;1.9&#xD;
&#xD;
          4. History of heparin-induced thrombocytopenia&#xD;
&#xD;
          5. Ischemic stroke within the past 2 weeks&#xD;
&#xD;
        Patients who meet the following criterion are excluded from the second randomization&#xD;
        (antiplatelet therapy vs. no antiplatelet therapy):&#xD;
&#xD;
        1. Ongoing or planned antiplatelet therapy, including aspirin monotherapy&#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>Marc S Sabatine, MD, MPH</last_name>
    <role>Study Chair</role>
    <affiliation>TIMI Study Group</affiliation>
  </overall_official>
  <overall_official>
    <last_name>David A Morrow, MD, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>TIMI Study Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02459</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>April 11, 2022</last_update_submitted>
  <last_update_submitted_qc>April 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Thrombosis</mesh_term>
    <mesh_term>Thromboembolism</mesh_term>
    <mesh_term>Venous Thromboembolism</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heparin</mesh_term>
    <mesh_term>Calcium heparin</mesh_term>
    <mesh_term>Enoxaparin</mesh_term>
    <mesh_term>Enoxaparin sodium</mesh_term>
    <mesh_term>Clopidogrel</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>May 18, 2023</submitted>
    <returned>June 9, 2023</returned>
    <submitted>July 14, 2023</submitted>
    <returned>August 4, 2023</returned>
    <submitted>August 29, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04409834
org study id: CCCTN/TIMI COVID-PACT
nct id: NCT04409834
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is a multicenter, open-label, 2x2 factorial, randomized-controlled trial in
      critically-ill patients with novel coronavirus disease 2019 (COVID-19) evaluating the
      efficacy and safety of full-dose vs. standard prophylactic dose anticoagulation and of
      antiplatelet vs. no antiplatelet therapy for prevention of venous and arterial thrombotic
      events.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Primary endpoint: Venous or arterial thrombotic events
time frame: 28 days or until hospital discharge, whichever earlier
description: Hierarchical composite: Death due to venous or arterial thrombosis, pulmonary embolism, clinically evident DVT, type 1 MI, ischemic stroke, systemic embolism or acute limb ischemia, or clinically silent DVT
measure: Key secondary endpoint: Clinically evident venous or arterial thrombotic events
time frame: 28 days or until hospital discharge, whichever earlier
description: Hierarchical composite: Death due to venous or arterial thrombosis, pulmonary embolism, clinically evident DVT, type 1 MI, ischemic stroke, systemic embolism or acute limb ischemia
arm group label: Full-dose anticoagulation + antiplatelet therapy
arm group type: Experimental
description: • Full-dose anticoagulation: Unfractionated heparin IV continuous targeting aPTT of 1.5-2.5X control, or Enoxaparin 1 mg/kg SC Q12h
• Anti-platelet therapy: Clopidogrel 300 mg PO x1, followed by clopidogrel 75 mg PO QD
arm group label: Full-dose anticoagulation + no antiplatelet therapy
arm group type: Experimental
description: • Full-dose anticoagulation: Unfractionated heparin IV continuous targeting aPTT of 1.5-2.5X control, or Enoxaparin 1 mg/kg SC Q12h
arm group label: Prophylactic anticoagulation + antiplatelet therapy
arm group type: Experimental
description: • Standard prophylactic anticoagulation: Enoxaparin 40 mg SC QD or Unfractionated heparin 5,000 IU SC TID
• Antiplatelet therapy: Clopidogrel 300 mg PO x1, followed by clopidogrel 75 mg PO QD
arm group label: Prophylactic anticoagulation + no antiplatelet therapy
arm group type: Active Comparator
description: • Standard prophylactic anticoagulation: Enoxaparin 40 mg SC QD or Unfractionated heparin 5,000 IU SC TID
intervention type: Drug
intervention name: Unfractionated Heparin IV
description: Unfractionated heparin IV targeting an aPTT of 1.5-2.5 times the control
arm group label: Full-dose anticoagulation + antiplatelet therapy
arm group label: Full-dose anticoagulation + no antiplatelet therapy
intervention type: Drug
intervention name: Enoxaparin 1 mg/kg
description: Enoxaparin 1 mg/kg SC Q12h
arm group label: Full-dose anticoagulation + antiplatelet therapy
arm group label: Full-dose anticoagulation + no antiplatelet therapy
intervention type: Drug
intervention name: Clopidogrel
description: Clopidogrel 300 mg PO x1, then clopidogrel 75 mg PO QD
arm group label: Full-dose anticoagulation + antiplatelet therapy
arm group label: Prophylactic anticoagulation + antiplatelet therapy
intervention type: Drug
intervention name: Unfractionated heparin SC
description: Unfractionated heparin 5,000 IU SC TID
arm group label: Prophylactic anticoagulation + antiplatelet therapy
arm group label: Prophylactic anticoagulation + no antiplatelet therapy
intervention type: Drug
intervention name: Enoxaparin 40 Mg/0.4 mL Injectable Solution
description: Enoxaparin 40 mg SC QD
arm group label: Prophylactic anticoagulation + antiplatelet therapy
arm group label: Prophylactic anticoagulation + no antiplatelet therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Marc S Sabatine, MD, MPH
role: Study Chair
affiliation: TIMI Study Group
last name: David A Morrow, MD, MPH
role: Principal Investigator
affiliation: TIMI Study Group
facility: 
country: United States
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Thrombosis
mesh term: Thromboembolism
mesh term: Venous Thromboembolism
mesh term: Heparin
mesh term: Calcium heparin
mesh term: Enoxaparin
mesh term: Enoxaparin sodium
mesh term: Clopidogrel
sharing ipd: No
submitted: May 18, 2023
returned: June 9, 2023
submitted: July 14, 2023
returned: August 4, 2023
submitted: August 29, 2023