<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/NCT04444700</url>
  </required_header>
  <id_info>
    <org_study_id>CAAE: 33109220.7.0000.0068</org_study_id>
    <nct_id>NCT04444700</nct_id>
  </id_info>
  <brief_title>A Pragmatic Randomized Controlled Trial of Therapeutic Anticoagulation Versus Standard Care as a Rapid Response to (SARS-CoV-2) COVID-19 Pandemic</brief_title>
  <acronym>RAPID-BRAZIL</acronym>
  <official_title>Utilização da Enoxaparina em Dose Anticoagulante em Pacientes Hospitalizados Com síndrome respiratória Aguda Grave Por COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Unity Health Toronto</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Vermont Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Sao Paulo General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Coagulopathy of COVID-19 afflicts approximately 20% of patients with severe COVID-19 and is&#xD;
      associated with need for critical care and death. COVID-19 coagulopathy is characterized by&#xD;
      elevated D-dimer, an indicator of fibrin formation and clot lysis, and a mildly prolonged&#xD;
      prothrombin time, suggestive of coagulation consumption. To date, it seems that COVID-19&#xD;
      coagulopathy manifests with thromboembolism, thus anticoagulation may be of benefit. We&#xD;
      propose to conduct a parallel pragmatic multi-centre open-label randomized controlled trial&#xD;
      to determine the effect of therapeutic anticoagulation compared to standard care in&#xD;
      hospitalized patients admitted for COVID-19 with an elevated D-dimer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      2-arm, parallel, pragmatic, multi-centre, open-label randomized controlled trial to determine&#xD;
      the effect of therapeutic anticoagulation, with low molecular weight heparin or&#xD;
      unfractionated heparin (high dose nomogram), compared to standard care in hospitalized&#xD;
      patients with COVID-19 and an elevated D-dimer on the composite outcome of intensive care&#xD;
      unit (ICU) admission, non-invasive positive pressure ventilation, invasive mechanical&#xD;
      ventilation or death at 28 days. Eligible participants will be randomized to one of two&#xD;
      treatment regimens, receiving either therapeutic anticoagulation or standard care until&#xD;
      discharged from hospital, death or day 28.&#xD;
&#xD;
      The primary composite outcome of ICU admission, non-invasive positive pressure ventilation,&#xD;
      invasive mechanical ventilation, or all-cause death up to 28 days.&#xD;
&#xD;
      Key secondary outcomes between study arms up to day 28 include:&#xD;
&#xD;
        1. All-cause death&#xD;
&#xD;
        2. Composite outcome of ICU admission or all-cause death&#xD;
&#xD;
        3. Composite outcome of mechanical ventilation or all-cause death&#xD;
&#xD;
        4. Major bleeding as defined by the ISTH Scientific and Standardization Committee&#xD;
           (ISTH-SSC) recommendation&#xD;
&#xD;
        5. Number of participants who received red blood cell transfusion (≥1 unit)&#xD;
&#xD;
        6. Number of participants with transfusion of platelets, frozen plasma, prothrombin complex&#xD;
           concentrate, cryoprecipitate and/or fibrinogen concentrate&#xD;
&#xD;
        7. Renal replacement therapy;&#xD;
&#xD;
        8. Number of hospital-free days alive&#xD;
&#xD;
        9. Number of ICU-free days alive&#xD;
&#xD;
       10. Number of ventilator-free days alive&#xD;
&#xD;
       11. Number of organ support-free days alive&#xD;
&#xD;
       12. Number of participants with venous thromboembolism&#xD;
&#xD;
       13. Number of participants with arterial thromboembolism&#xD;
&#xD;
       14. Number of participants with heparin induced thrombocytopenia&#xD;
&#xD;
       15. Changes in D-dimer up to day 3&#xD;
&#xD;
      The treatment arm is therapeutic anticoagulation with low molecular weight heparin (LMWH) or&#xD;
      unfractionated heparin (UFH, high dose nomogram). The choice of LMWH versus UFH will be at&#xD;
      the clinician's discretion. LMWH options include: Tinzaparin, Enoxaparin, or Dalteparin. UFH&#xD;
      will be administered using a weight-based nomogram with titration according to the&#xD;
      center-specific protocol. Therapeutic anticoagulation will be administered until discharged&#xD;
      from hospital, 28 days or death. If the patient is admitted to the ICU or requiring&#xD;
      ventilatory support, we recommend continuation of the allocated treatment as long as the&#xD;
      treating physician is in agreement. The standard care arm is the administration of LMWH, UFH&#xD;
      or fondaparinux at thromboprophylactic doses in the absence of contraindication.&#xD;
&#xD;
      No study specific bloodwork will be ordered aside from a single D-dimer test (if not&#xD;
      collected through standard of care) up to and including day 3 after randomization for all&#xD;
      participants in both study arms. In those on the active treatment arm who are receiving UFH,&#xD;
      the aPTT or UFH anti-Xa will be drawn according to local institutional UFH nomogram protocol&#xD;
      guidance. All laboratory results will be collected from standard of care from admission to&#xD;
      hospital discharge, death or 28 days, where available. An optional biobanking component will&#xD;
      collect blood at baseline and 2 follow up time points.&#xD;
&#xD;
      This study will immediately impact the clinical care of patients with severe COVID-19&#xD;
      internationally, whether the findings are positive or negative, as COVID-19 coagulopathy is a&#xD;
      highly prevalent complication of severe COVID-19 and may precede the respiratory&#xD;
      manifestations that characterize it.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 4, 2020</start_date>
  <completion_date type="Actual">October 14, 2021</completion_date>
  <primary_completion_date type="Actual">May 10, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>This study is a 2-arm, parallel, pragmatic, multi-centre, open-label randomized controlled trial to determine the effect of therapeutic anticoagulation on the composite outcome of ICU admission, mechanical ventilation and/or death in hospitalized patients with COVID-19.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>None (Open Label) Blinding of participants, clinical research staff, and clinicians is not possible due to the nature of the intervention. However, the biostatisticians will be blinded at the data analysis phase.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Composite outcome of ICU admission (yes/no), non-invasive positive pressure ventilation (yes/no), invasive mechanical ventilation (yes/no), or all-cause death (yes/no) up to 28 days.</measure>
    <time_frame>up to 28 days</time_frame>
    <description>Composite outcome of ICU admission (yes/no), non-invasive positive pressure ventilation (yes/no), invasive mechanical ventilation (yes/no), or all-cause death (yes/no) up to 28 days.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>All-cause death</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>All-cause death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite outcome of ICU admission or all-cause death</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Composite outcome of ICU admission or all-cause death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Composite outcome of mechanical ventilation or all-cause death</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Composite outcome of mechanical ventilation or all-cause death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Major bleeding</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Major bleeding as defined by the ISTH Scientific and Standardization Committee (ISTH-SSC) recommendation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Red blood cell transfusion</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Red Blood Cell transfusion (greater than or equal to 1 unit)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transfusion of platelets, frozen plasma, prothrombin complex concentrate, cryoprecipiate and/or fibrinogen concentrate</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Transfusion of platelets, frozen plasma, prothrombin complex concentrate, cryoprecipiate and/or fibrinogen concentrate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal replacement therapy</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Renal replacement therapy defined as continuous renal replacement therapy or intermittent hemodialysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital-free days alive up to day 28</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Hospital-free days alive up to day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU-free days alive up to day 28</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>ICU-free days alive up to day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ventilator-free days alive up to day 28</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Ventilator-free days alive up to day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Organ support-free days alive up to day 28</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Organ support-free days alive up to day 28</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Venous thromboembolism</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Venous thromboembolism</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Arterial thromboembolism</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Arterial thromboembolism</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heparin induced thrombocytopenia</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Heparin induced thrombocytopenia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in D-dimer up to day 3</measure>
    <time_frame>Up to day 3</time_frame>
    <description>D-dimer</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">465</enrollment>
  <condition>COVID</condition>
  <condition>Coronavirus Infection</condition>
  <condition>Severe Acute Respiratory Syndrome</condition>
  <condition>Thromboembolism, Venous</condition>
  <condition>Anticoagulants and Bleeding Disorders</condition>
  <arm_group>
    <arm_group_label>Therapeutic anticoagulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Therapeutic anticoagulation with LMWH or UFH (high dose nomogram). The choice of LMWH versus UFH will be at the clinician's discretion and dependent on local institutional supply. Therapeutic anticoagulation will be administered until discharged from hospital, 28 days or death. If the patient is admitted to the ICU or requiring ventilatory support, we recommend continuation of the allocated treatment as long as the treating physician is in agreement.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Administration of LMWH, UFH or fondaparinux at thromboprophylactic doses for acutely ill hospitalized medical patients, in the absence of contraindication, is considered standard care.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Therapeutic anticoagulation</intervention_name>
    <description>The choice of low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) will be at the clinician's discretion. LMWH options include: Tinzaparin, Enoxaparin or Dalteparin. UFH will be administered using a weight-based nomogram with titration according to center-specific institutional protocol.</description>
    <arm_group_label>Therapeutic anticoagulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        The inclusion criteria are:&#xD;
&#xD;
          1. laboratory confirmed diagnosis of SARS-CoV-2 via reverse transcriptase polymerase&#xD;
             chain reaction as per the World Health Organization protocol or by nucleic acid based&#xD;
             isothermal amplification.Positive test prior to hospital admission OR within first 5&#xD;
             days (i.e. 120 hours) after hospital admission;&#xD;
&#xD;
          2. admitted to hospital for COVID-19;&#xD;
&#xD;
          3. one D-dimer value above ULN (5 days (i.e. 120 hours) of hospital admission) and&#xD;
             either: a) D-Dimer ≥2 times ULN; or b) D-dimer above ULN and oxygen saturation ≤ 93%&#xD;
             on room air;&#xD;
&#xD;
          4. ≥18 years of age;&#xD;
&#xD;
          5. informed consent from the patient (or legally authorized substitute decision maker).&#xD;
&#xD;
        The exclusion criteria are:&#xD;
&#xD;
          1. pregnancy;&#xD;
&#xD;
          2. hemoglobin &lt;80 g/L in the last 72 hours;&#xD;
&#xD;
          3. platelet count &lt;50 x 10^9/L in the last 72 hours;&#xD;
&#xD;
          4. known fibrinogen &lt;1.5 g/L (if testing deemed clinically indicated by the treating&#xD;
             physician prior to the initiation of anticoagulation);&#xD;
&#xD;
          5. known INR &gt;1.8 (if testing deemed clinically indicated by the treating physician prior&#xD;
             to the initiation of anticoagulation);&#xD;
&#xD;
          6. patient already on intermediate dosing of LMWH that cannot be changed (determination&#xD;
             of what constitutes an intermediate dose is to be at the discretion of the treating&#xD;
             clinician taking the local institutional thromboprophylaxis protocol for high risk&#xD;
             patients into consideration);&#xD;
&#xD;
          7. patient already on therapeutic anticoagulation at the time of screening (low or high&#xD;
             dose nomogram UFH, LMWH, warfarin, direct oral anticoagulant (any dose of dabigatran,&#xD;
             apixaban, rivaroxaban, edoxaban);&#xD;
&#xD;
          8. patient on dual antiplatelet therapy, when one of the agents cannot be stopped safely;&#xD;
&#xD;
          9. known bleeding within the last 30 days requiring emergency room presentation or&#xD;
             hospitalization;&#xD;
&#xD;
         10. known history of a bleeding disorder of an inherited or active acquired bleeding&#xD;
             disorder;&#xD;
&#xD;
         11. known history of heparin-induced thrombocytopenia;&#xD;
&#xD;
         12. known allergy to UFH or LMWH;&#xD;
&#xD;
         13. admitted to the intensive care unit at the time of screening;&#xD;
&#xD;
         14. treated with non-invasive positive pressure ventilation or invasive mechanical&#xD;
             ventilation at the time of screening (of note: high flow oxygen delivery via nasal&#xD;
             cannula is acceptable and is not an exclusion criterion).&#xD;
&#xD;
         15. imminent death according to the judgement of the most responsible physician&#xD;
&#xD;
         16. enrollment in another clinical trial of antithrombotic therapy involving pre-intensive&#xD;
             care unit hospitalized patients&#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>Peter Juni, MD, FESC</last_name>
    <role>Principal Investigator</role>
    <affiliation>St Michael's Hospital, Li Ka Shing Knowledge Institute, University of Toronto</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Elnara M Negri, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Laboratório de Investigação Médica da FMUSP</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Heraldo P de Souza, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Disciplina de Emergências Clínicas, Hospital das Clínicas da FMUSP</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hassan Rahhal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Disciplina de Emergências Clínicas, Hospital das Clínicas da FMUSP</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital das Clínicas da FMUSP</name>
      <address>
        <city>São Paulo</city>
        <state>SP</state>
        <zip>05402-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>June 22, 2020</study_first_submitted>
  <study_first_submitted_qc>June 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>October 25, 2021</last_update_submitted>
  <last_update_submitted_qc>October 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 26, 2021</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>Coronavirus Infections</mesh_term>
    <mesh_term>Severe Acute Respiratory Syndrome</mesh_term>
    <mesh_term>Thromboembolism</mesh_term>
    <mesh_term>Hemostatic Disorders</mesh_term>
    <mesh_term>Venous Thromboembolism</mesh_term>
    <mesh_term>Blood Coagulation Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04444700
org study id: CAAE: 33109220.7.0000.0068
nct id: NCT04444700
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Coagulopathy of COVID-19 afflicts approximately 20% of patients with severe COVID-19 and is
      associated with need for critical care and death. COVID-19 coagulopathy is characterized by
      elevated D-dimer, an indicator of fibrin formation and clot lysis, and a mildly prolonged
      prothrombin time, suggestive of coagulation consumption. To date, it seems that COVID-19
      coagulopathy manifests with thromboembolism, thus anticoagulation may be of benefit. We
      propose to conduct a parallel pragmatic multi-centre open-label randomized controlled trial
      to determine the effect of therapeutic anticoagulation compared to standard care in
      hospitalized patients admitted for COVID-19 with an elevated D-dimer.
2-arm, parallel, pragmatic, multi-centre, open-label randomized controlled trial to determine
      the effect of therapeutic anticoagulation, with low molecular weight heparin or
      unfractionated heparin (high dose nomogram), compared to standard care in hospitalized
      patients with COVID-19 and an elevated D-dimer on the composite outcome of intensive care
      unit (ICU) admission, non-invasive positive pressure ventilation, invasive mechanical
      ventilation or death at 28 days. Eligible participants will be randomized to one of two
      treatment regimens, receiving either therapeutic anticoagulation or standard care until
      discharged from hospital, death or day 28.

      The primary composite outcome of ICU admission, non-invasive positive pressure ventilation,
      invasive mechanical ventilation, or all-cause death up to 28 days.

      Key secondary outcomes between study arms up to day 28 include:

        1. All-cause death

        2. Composite outcome of ICU admission or all-cause death

        3. Composite outcome of mechanical ventilation or all-cause death

        4. Major bleeding as defined by the ISTH Scientific and Standardization Committee
           (ISTH-SSC) recommendation

        5. Number of participants who received red blood cell transfusion (≥1 unit)

        6. Number of participants with transfusion of platelets, frozen plasma, prothrombin complex
           concentrate, cryoprecipitate and/or fibrinogen concentrate

        7. Renal replacement therapy;

        8. Number of hospital-free days alive

        9. Number of ICU-free days alive

       10. Number of ventilator-free days alive

       11. Number of organ support-free days alive

       12. Number of participants with venous thromboembolism

       13. Number of participants with arterial thromboembolism

       14. Number of participants with heparin induced thrombocytopenia

       15. Changes in D-dimer up to day 3

      The treatment arm is therapeutic anticoagulation with low molecular weight heparin (LMWH) or
      unfractionated heparin (UFH, high dose nomogram). The choice of LMWH versus UFH will be at
      the clinician's discretion. LMWH options include: Tinzaparin, Enoxaparin, or Dalteparin. UFH
      will be administered using a weight-based nomogram with titration according to the
      center-specific protocol. Therapeutic anticoagulation will be administered until discharged
      from hospital, 28 days or death. If the patient is admitted to the ICU or requiring
      ventilatory support, we recommend continuation of the allocated treatment as long as the
      treating physician is in agreement. The standard care arm is the administration of LMWH, UFH
      or fondaparinux at thromboprophylactic doses in the absence of contraindication.

      No study specific bloodwork will be ordered aside from a single D-dimer test (if not
      collected through standard of care) up to and including day 3 after randomization for all
      participants in both study arms. In those on the active treatment arm who are receiving UFH,
      the aPTT or UFH anti-Xa will be drawn according to local institutional UFH nomogram protocol
      guidance. All laboratory results will be collected from standard of care from admission to
      hospital discharge, death or 28 days, where available. An optional biobanking component will
      collect blood at baseline and 2 follow up time points.

      This study will immediately impact the clinical care of patients with severe COVID-19
      internationally, whether the findings are positive or negative, as COVID-19 coagulopathy is a
      highly prevalent complication of severe COVID-19 and may precede the respiratory
      manifestations that characterize it.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This study is a 2-arm, parallel, pragmatic, multi-centre, open-label randomized controlled trial to determine the effect of therapeutic anticoagulation on the composite outcome of ICU admission, mechanical ventilation and/or death in hospitalized patients with COVID-19.
primary purpose: Treatment
masking: None (Open Label)
masking description: None (Open Label) Blinding of participants, clinical research staff, and clinicians is not possible due to the nature of the intervention. However, the biostatisticians will be blinded at the data analysis phase.
measure: Composite outcome of ICU admission (yes/no), non-invasive positive pressure ventilation (yes/no), invasive mechanical ventilation (yes/no), or all-cause death (yes/no) up to 28 days.
time frame: up to 28 days
description: Composite outcome of ICU admission (yes/no), non-invasive positive pressure ventilation (yes/no), invasive mechanical ventilation (yes/no), or all-cause death (yes/no) up to 28 days.
measure: All-cause death
time frame: Up to 28 days
description: All-cause death
measure: Composite outcome of ICU admission or all-cause death
time frame: Up to 28 days
description: Composite outcome of ICU admission or all-cause death
measure: Composite outcome of mechanical ventilation or all-cause death
time frame: Up to 28 days
description: Composite outcome of mechanical ventilation or all-cause death
measure: Major bleeding
time frame: Up to 28 days
description: Major bleeding as defined by the ISTH Scientific and Standardization Committee (ISTH-SSC) recommendation
measure: Red blood cell transfusion
time frame: Up to 28 days
description: Red Blood Cell transfusion (greater than or equal to 1 unit)
measure: Transfusion of platelets, frozen plasma, prothrombin complex concentrate, cryoprecipiate and/or fibrinogen concentrate
time frame: Up to 28 days
description: Transfusion of platelets, frozen plasma, prothrombin complex concentrate, cryoprecipiate and/or fibrinogen concentrate
measure: Renal replacement therapy
time frame: Up to 28 days
description: Renal replacement therapy defined as continuous renal replacement therapy or intermittent hemodialysis
measure: Hospital-free days alive up to day 28
time frame: Up to 28 days
description: Hospital-free days alive up to day 28
measure: ICU-free days alive up to day 28
time frame: Up to 28 days
description: ICU-free days alive up to day 28
measure: Ventilator-free days alive up to day 28
time frame: Up to 28 days
description: Ventilator-free days alive up to day 28
measure: Organ support-free days alive up to day 28
time frame: Up to 28 days
description: Organ support-free days alive up to day 28
measure: Venous thromboembolism
time frame: Up to 28 days
description: Venous thromboembolism
measure: Arterial thromboembolism
time frame: Up to 28 days
description: Arterial thromboembolism
measure: Heparin induced thrombocytopenia
time frame: Up to 28 days
description: Heparin induced thrombocytopenia
measure: Changes in D-dimer up to day 3
time frame: Up to day 3
description: D-dimer
arm group label: Therapeutic anticoagulation
arm group type: Experimental
description: Therapeutic anticoagulation with LMWH or UFH (high dose nomogram). The choice of LMWH versus UFH will be at the clinician's discretion and dependent on local institutional supply. Therapeutic anticoagulation will be administered until discharged from hospital, 28 days or death. If the patient is admitted to the ICU or requiring ventilatory support, we recommend continuation of the allocated treatment as long as the treating physician is in agreement.
arm group label: Standard care
arm group type: No Intervention
description: Administration of LMWH, UFH or fondaparinux at thromboprophylactic doses for acutely ill hospitalized medical patients, in the absence of contraindication, is considered standard care.
intervention type: Drug
intervention name: Therapeutic anticoagulation
description: The choice of low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) will be at the clinician's discretion. LMWH options include: Tinzaparin, Enoxaparin or Dalteparin. UFH will be administered using a weight-based nomogram with titration according to center-specific institutional protocol.
arm group label: Therapeutic anticoagulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Peter Juni, MD, FESC
role: Principal Investigator
affiliation: St Michael's Hospital, Li Ka Shing Knowledge Institute, University of Toronto
last name: Elnara M Negri, MD, PhD
role: Principal Investigator
affiliation: Laboratório de Investigação Médica da FMUSP
last name: Heraldo P de Souza, MD, PhD
role: Principal Investigator
affiliation: Disciplina de Emergências Clínicas, Hospital das Clínicas da FMUSP
last name: Hassan Rahhal, MD
role: Principal Investigator
affiliation: Disciplina de Emergências Clínicas, Hospital das Clínicas da FMUSP
facility: 
country: Brazil
responsible party type: Sponsor
mesh term: Coronavirus Infections
mesh term: Severe Acute Respiratory Syndrome
mesh term: Thromboembolism
mesh term: Hemostatic Disorders
mesh term: Venous Thromboembolism
mesh term: Blood Coagulation Disorders
sharing ipd: No