<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/NCT04483960</url>
  </required_header>
  <id_info>
    <org_study_id>ERM 62646-A</org_study_id>
    <nct_id>NCT04483960</nct_id>
  </id_info>
  <brief_title>Australasian COVID-19 Trial (ASCOT) ADAptive Platform Trial</brief_title>
  <acronym>ASCOT ADAPT</acronym>
  <official_title>A Multi-centre Randomised Adaptive Platform Clinical Trial to Assess Clinical, Virological and Immunological Outcomes in Patients With SARS-CoV-2 Infection (COVID-19)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Melbourne</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Peter Doherty Institute for Infection and Immunity</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Australasian Society for Infectious Diseases</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Middlemore Clinical Trials</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The George Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hunter Medical Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The University of Queensland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Melbourne</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>
      An International Multi-Centre Randomised Adaptive Platform Clinical Trial to Assess the&#xD;
      Clinical, Virological and Immunological Outcomes in Patients with SARS-CoV-2 Infection&#xD;
      (COVID-19).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled adaptive&#xD;
      platform trial. The study design will allow harmonisation with existing frameworks such as&#xD;
      the Sentinel Travellers Research Preparedness Platform for Emerging Infectious Diseases&#xD;
      (SETREP-ID) and the Randomised, embedded, multifactorial adaptive platform trial for&#xD;
      community acquired pneumonia (REMAP-CAP) study.&#xD;
&#xD;
      Platform trials allow multiple questions to be evaluated simultaneously and sequentially&#xD;
      within the platform, and evaluate interaction between different treatment options, to achieve&#xD;
      the goal of determining the optimal combination of treatments for the disease as rapidly as&#xD;
      possible. The overarching objective of ASCOT-ADAPT is to identify the regimen (combination of&#xD;
      interventions) associated with the highest chance of survival free of advanced respiratory&#xD;
      support or vasopressor / inotropic support at 28 days after randomisation, in adults&#xD;
      hospitalised with COVID-19 but not requiring ICU-level care at baseline.&#xD;
&#xD;
      In the initial implementation of the adaptive platform, recruiting sites have the option to&#xD;
      participate in one or more of three treatment domains. Consented participants will then be&#xD;
      able to choose whether to be enrolled into one or more available domains concurrently.&#xD;
      Participants will then be randomised to the corresponding interventions:&#xD;
&#xD;
      Intervention domain A (antiviral):&#xD;
&#xD;
      Participants will be randomised using response adaptive randomisation (RAR) on day 1 to&#xD;
      receive either i) standard of care without nafamostat; or ii) standard of care with&#xD;
      nafamostat&#xD;
&#xD;
      (Domain Closed) Intervention domain B (antibody): Participants will be randomised using&#xD;
      response adaptive randomisation (RAR) on day 1 to receive either i) standard of care without&#xD;
      hyperimmune globulin; or ii) standard of care with hyperimmune globulin&#xD;
&#xD;
      (Domain Closed) Intervention domain C (anticoagulation): Participants will be randomised&#xD;
      using response adaptive randomisation (RAR) on day 1 to receive either i) standard dose&#xD;
      thromboprophylaxis; or ii) intermediate dose thromboprophylaxis; or iii) therapeutic&#xD;
      anticoagulation&#xD;
&#xD;
      Daily data will be collected for the first 28 days or until discharge, whichever is earlier.&#xD;
      There will be a core dataset collected for all patients at all sites and enhanced and&#xD;
      research data and biological samples for sites with capacity. Participants will be followed&#xD;
      up at Day 90.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 28, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</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>Factorial Assignment</intervention_model>
    <intervention_model_description>Participants enrolled into the study have the option of deciding whether to be randomised in one or more (if available) treatment domains concurrently, if they meet the eligibility criteria.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>This is an open-label study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Death from any cause or requirement of new intensive respiratory support (invasive or non-invasive ventilation) or vasopressor/inotropic support.</measure>
    <time_frame>28 days</time_frame>
    <description>This includes any participant who receives non-invasive mechanical ventilation (either CPAP or BIPAP, apart from the below considerations) any time after enrolment even if not transferred to ICU. It does NOT include the use of humidified high-flow nasal prong oxygen.&#xD;
Participants on pre-existing home BiPAP or CPAP will not be considered to have met the primary outcome unless they have either i. required invasive mechanical ventilation (i.e. intubation), or ii. graduated from CPAP only whilst asleep to BiPAP at any time, or iii. graduated from BiPAP only whilst asleep to BiPAP for &gt;12 hours/day, or iv. died by day 28</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to clinical recovery</measure>
    <time_frame>28 days</time_frame>
    <description>Defined as the first day, during the 28 days after enrolment, on which a patient satisfies categories 1, 2, or 3 on the WHO eight-point ordinal outcome scale. For the purposes of this outcome measure, it will be assumed that the participant is not hospitalised on the first day following discharge.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WHO 8-point ordinal outcome scale</measure>
    <time_frame>28 days</time_frame>
    <description>The ordinal score is:&#xD;
Not hospitalised, no limitations on activities&#xD;
Not hospitalised, limitation on activities&#xD;
Hospitalised, not requiring supplemental oxygen and no longer requiring ongoing medical care (used if hospitalization was extended for infection control purposes)&#xD;
Hospitalised, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or other medical conditions)&#xD;
Hospitalised, requiring supplemental oxygen&#xD;
Hospitalised, on non-invasive ventilation or high flow oxygen devices&#xD;
Hospitalised, on invasive mechanical ventilation or ECMO&#xD;
Death.&#xD;
Admission to a Hospital in the Home unit is not counted as hospitalisation for the purposes of this ordinal scale. Patients who have been admitted to hospital and transferred to a Hospital in the Home unit will be assessed as either ordinal score 1 or 2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>28 days and 90 days</time_frame>
    <description>All-cause mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days alive and free of hospital</measure>
    <time_frame>28 days</time_frame>
    <description>Number of days&#xD;
Days spent in a Hospital in the Home unit will not be counted as days in hospital as hospital means 'acute-care hospital' for the purposes of this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days alive and free of invasive or non-invasive ventilation</measure>
    <time_frame>28 days</time_frame>
    <description>Number of days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Shortness of breath</measure>
    <time_frame>28 days and 90 days</time_frame>
    <description>Patient reported outcome.&#xD;
Dichotomous comparison of a subjective measure of shortness of breath such as: &quot;Are you currently experiencing shortness of breath that you didn't have before you got COVID, or which is worse now than before you got COVID?&quot;&#xD;
Ordinal comparison of the modified Medical Research Council (mMRC) breathlessness scale:&#xD;
Modified Medical Research Council (mMRC) Dyspnoea Scale for grading the severity of breathlessness during daily activities:&#xD;
0 - I only get breathless with strenuous exercise&#xD;
- I get short of breath when hurrying on level ground or walking up a slight hill&#xD;
- On level ground, I walk slower than people of the same age because of breathlessness, or I have to stop for breath when walking at my own pace on the level&#xD;
- I stop for breath after walking about 100 metres or after a few minutes on level ground&#xD;
- I am too breathless to leave the house or I am breathless when dressing or undressing</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life</measure>
    <time_frame>28 days and 90 days</time_frame>
    <description>Measured by the EQ-5D-5L questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antiviral domain-specific outcome: Viral clearance</measure>
    <time_frame>3 and 7 days</time_frame>
    <description>Proportion of patients with negative SARS-CoV-2 RT-PCR from upper or lower respiratory tract samples, for those with results available.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antiviral domain-specific outcome: Viral load</measure>
    <time_frame>3 and 7 days</time_frame>
    <description>Changes in cycle threshold value in RT-PCR for SARS-CoV-2 from baseline to day 3 and from baseline to day 7, for those with results available from the same respiratory tract sample type.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antiviral domain-specific outcome: Safety (Liver enzymes)</measure>
    <time_frame>Up to day 28 or day of discharge from hospital, whichever is earlier</time_frame>
    <description>o Elevation of Alanine Transaminase (ALT) or Aspartate Transaminase (AST) to &gt;5x upper limit of normal</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antiviral domain-specific outcome: Safety (potassium)</measure>
    <time_frame>Up to day 28 or day of discharge from hospital, whichever is earlier</time_frame>
    <description>o Elevation of serum potassium to &gt;5.5 mmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antiviral domain-specific outcome: Safety (sodium)</measure>
    <time_frame>Up to day 28 or day of discharge from hospital, whichever is earlier</time_frame>
    <description>o Decrease of serum sodium to &lt;125 mmol/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antiviral domain-specific outcome: Safety (bleeding)</measure>
    <time_frame>Up to day 28 or day of discharge from hospital, whichever is earlier</time_frame>
    <description>o Major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antiviral domain-specific outcome: Safety (thrombophlebitis)</measure>
    <time_frame>Up to day 28 or day of discharge from hospital, whichever is earlier</time_frame>
    <description>o Thrombophlebitis/vasculitis at IV line site</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antiviral domain-specific outcome: serious adverse reactions</measure>
    <time_frame>28 days</time_frame>
    <description>Any safety event that, in the judgment of the investigator, is both serious and either possibly, probably or definitely related to the study intervention(s).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anticoagulation domain-specific outcome: Confirmed deep venous thrombosis</measure>
    <time_frame>28 days</time_frame>
    <description>Yes/No</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anticoagulation domain-specific outcome: Confirmed pulmonary embolus</measure>
    <time_frame>28 days</time_frame>
    <description>Yes/No</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anticoagulation domain-specific outcome: Confirmed acute myocardial infarction</measure>
    <time_frame>28 days</time_frame>
    <description>Yes/No</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anticoagulation domain-specific outcome: Confirmed ischemic cerebrovascular event</measure>
    <time_frame>28 days</time_frame>
    <description>Yes/No</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anticoagulation domain-specific outcome: Major bleeding</measure>
    <time_frame>28 days</time_frame>
    <description>Yes/No - As defined by International Society on Thrombosis and Haemostasis (ISTH). Site of bleeding and which of the ISTH criteria are met will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anticoagulation domain-specific outcome: Clinically relevant non-major bleeding</measure>
    <time_frame>28 days</time_frame>
    <description>Yes/No - As defined by International Society on Thrombosis and Haemostasis (ISTH).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anticoagulation domain-specific outcome: Heparin-induced thrombocytopenia (HIT)</measure>
    <time_frame>28 days</time_frame>
    <description>Yes/No - During index hospitalisation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anticoagulation domain-specific outcome: Other confirmed thrombotic event</measure>
    <time_frame>28 days</time_frame>
    <description>Yes/No - During index hospitalisation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibody domain-specific outcome: Serious treatment-related adverse events</measure>
    <time_frame>Within 24 hours of treatment</time_frame>
    <description>Including:&#xD;
Serious allergic reaction or anaphylaxis&#xD;
Transfusion-related acute lung injury (TRALI)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibody domain-specific outcome: Haemolysis</measure>
    <time_frame>Within 72 hours of last transfusion</time_frame>
    <description>Yes/No</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibody domain-specific outcome: Confirmed arterial thrombosis</measure>
    <time_frame>28 days</time_frame>
    <description>Yes/No - acute myocardial infarction, ischaemic cerebrovascular event, other</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibody domain-specific outcome: Confirmed venous thrombosis</measure>
    <time_frame>28 days</time_frame>
    <description>Yes/No - deep vein thrombosis, pulmonary embolus, other</description>
  </secondary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Anticipated">2400</enrollment>
  <condition>SARS-CoV-2 Infection (COVID-19)</condition>
  <arm_group>
    <arm_group_label>Antiviral - Standard of care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Standard of care without nafamostat mesilate</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Antiviral - nafamostat mesilate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nafamostat continuous IV infusion for 7 days or until day of hospital discharge at a dose of 0.2mg/kg/hour. No adjustment in dose is needed for renal impairment, including for renal dialysis. The daily dose of nafamostat should be administered in 500 mL (rate of infusion 20.8 mL/hour) of normal saline. Normal saline is recommended (due to the tendency for patients with COVID-19 towards hyponatraemia) but not mandated, and 5% dextrose would be acceptable if felt clinically appropriate.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>(Arm Closed) Anticoagulation - standard dose thromboprophylaxis</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will be administered a standard thromboprophylactic dose of low molecular weight heparin, choice of agent according to availability and local practice at the participating site.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>(Arm Closed) Anticoagulation - intermediate dose thromboprophylaxis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be administered an intermediate dose of low molecular weight heparin, choice of agent according to availability and local practice at the participating site. The maximum dose of enoxaparin will be 120 mg/d, tinzaparin 125 IU/kg/day (not available within Australia), and Dalteparin 15,000 IU/d.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>(Arm Closed) Anticoagulation - therapeutic anticoagulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Therapeutic anticoagulation administered with LMWH daily until hospital discharge, admission to ICU or for a maximum of 28 days from randomisation. Choice of LMWH according to availability and local practice at the participating site</description>
  </arm_group>
  <arm_group>
    <arm_group_label>(Arm Closed) Antibody - Standard of Care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No hyperimmune globulin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>(Arm Closed) Antibody - hyperimmune globulin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 doses of 30mL (3x10mL vials) of COVID-19 Hyper-Immunoglobulin (Human) given over 2 days within 48 hours of randomisation</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nafamostat Mesilate</intervention_name>
    <description>Nafamostat continuous IV infusion for 7 days or until day of hospital discharge at a dose of 0.2mg/kg/hour. No adjustment in dose is needed for renal impairment, including for renal dialysis. The daily dose of nafamostat should be administered in 500 mL (rate of infusion 20.8 mL/hour) of normal saline. Normal saline is recommended (due to the tendency for patients with COVID-19 towards hyponatraemia) but not mandated, and 5% dextrose would be acceptable if felt clinically appropriate.</description>
    <arm_group_label>Antiviral - nafamostat mesilate</arm_group_label>
    <other_name>Nafabelltan</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enoxaparin</intervention_name>
    <description>Patients will be administered either a standard dose, intermediate dose or therapeutic anticoagulation of low molecular weight heparin (depending on assigned arm), choice of agent according to availability and local practice at the participating site.&#xD;
The maximum dose of Enoxaparin will be 1mg/kg q12h or 1.5mg/kg q24h.</description>
    <arm_group_label>(Arm Closed) Anticoagulation - intermediate dose thromboprophylaxis</arm_group_label>
    <arm_group_label>(Arm Closed) Anticoagulation - standard dose thromboprophylaxis</arm_group_label>
    <arm_group_label>(Arm Closed) Anticoagulation - therapeutic anticoagulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dalteparin</intervention_name>
    <description>Patients will be administered either a standard dose, intermediate dose or therapeutic anticoagulation of low molecular weight heparin (depending on assigned arm), choice of agent according to availability and local practice at the participating site.&#xD;
The maximum dose of Dalteparin will be 100IU/kg q12h or 200IU/kg q24h.</description>
    <arm_group_label>(Arm Closed) Anticoagulation - intermediate dose thromboprophylaxis</arm_group_label>
    <arm_group_label>(Arm Closed) Anticoagulation - standard dose thromboprophylaxis</arm_group_label>
    <arm_group_label>(Arm Closed) Anticoagulation - therapeutic anticoagulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tinzaparin</intervention_name>
    <description>Patients will be administered either a standard dose, intermediate dose or therapeutic anticoagulation of low molecular weight heparin (depending on assigned arm), choice of agent according to availability and local practice at the participating site.&#xD;
The maximum dose of Tinzaparin will be 175IU/kg q24h (not available within Australia).</description>
    <arm_group_label>(Arm Closed) Anticoagulation - intermediate dose thromboprophylaxis</arm_group_label>
    <arm_group_label>(Arm Closed) Anticoagulation - standard dose thromboprophylaxis</arm_group_label>
    <arm_group_label>(Arm Closed) Anticoagulation - therapeutic anticoagulation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Hyperimmune globulin</intervention_name>
    <description>2 doses of 30mL (3x10mL vials) of COVID-19 Hyper-Immunoglobulin (Human) given over 2 days within 48 hours of randomisation. Three vials will have approximately 10500 AU of neutralising antibodies, equivalent to approximately 200mL of convalescent plasma</description>
    <arm_group_label>(Arm Closed) Antibody - hyperimmune globulin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Platform Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years&#xD;
&#xD;
          2. Admitted to an acute-care hospital&#xD;
&#xD;
          3. Confirmed SARS-CoV-2 by nucleic acid testing or rapid antigen testing in the 14 days&#xD;
             prior to randomisation&#xD;
&#xD;
          4. Able to be randomised within 14 days of symptom onset&#xD;
&#xD;
          5. At least one symptom or sign attributable to SARS-CoV-2 infection&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        A. Overall platform exclusions:&#xD;
&#xD;
          1. Currently receiving acute intensive respiratory support (invasive or non-invasive&#xD;
             mechanical ventilation) or vasopressor/inotropic support. Note, participants already&#xD;
             on community based non-invasive ventilation (either CPAP or BiPAP) can still be&#xD;
             recruited. Humidified high flow nasal oxygen will not be considered an exclusion&#xD;
             criterion.&#xD;
&#xD;
          2. Previous participation in the trial&#xD;
&#xD;
          3. Treating team deems enrolment in the study is not in the best interests of the patient&#xD;
&#xD;
          4. Death is deemed to be imminent and inevitable within the next 24 hours&#xD;
&#xD;
          5. Either the patient or their primary treating clinician are not committed to active&#xD;
             treatment.&#xD;
&#xD;
        This criterion seeks to exclude those patients where supportive comfort measures only are&#xD;
        being provided. Patients who are planned for active ward management with a clear aim to&#xD;
        improve survival, even if intensive care unit level support is not being offered, should&#xD;
        still be included.&#xD;
&#xD;
        B. Domain A (Antiviral) intervention-level exclusions:&#xD;
&#xD;
        Criteria that exclude a patient from one or more interventions are:&#xD;
&#xD;
        Nafamostat:&#xD;
&#xD;
          -  Known current decompensated liver disease (Child-Pugh B or C)&#xD;
&#xD;
          -  The treating clinician intends to continue or commence therapeutic anticoagulation&#xD;
&#xD;
          -  A current or recurrent condition with a high risk of major bleeding (e.g. bleeding&#xD;
             disorder), or a baseline coagulation profile (within the previous 3 days) that&#xD;
             indicates a high risk of bleeding, that would be considered a contraindication to&#xD;
             receive therapeutic anticoagulation&#xD;
&#xD;
          -  Serum Potassium &gt;5.5 mmol/L (based on most recent blood test result collected as part&#xD;
             of routine care within the previous 3 days)&#xD;
&#xD;
          -  Serum Sodium &lt;120 mmol/L (based on most recent blood test result collected as part of&#xD;
             routine care within the previous 3 days)&#xD;
&#xD;
          -  Hypersensitivity to nafamostat&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Currently receiving or have received nafamostat in the past 7 days&#xD;
&#xD;
          -  Decompensated heart failure or renal dialysis and clinician believes an extra 500mL&#xD;
             fluid/day would be detrimental There are no domain-level exclusions for the antiviral&#xD;
             domain.&#xD;
&#xD;
        C. Domain B (Antibody - hyperimmunoglobulin or standard care) specific exclusions:&#xD;
&#xD;
          1. Participant has already received treatment with SARS-CoV-2-specific immunoglobulin&#xD;
             therapy (convalescent plasma, hyperimmune globulin or monoclonal antibody) within 3&#xD;
             months prior to enrolment&#xD;
&#xD;
          2. Treating team deems enrolment in antibody intervention is not in the best interests of&#xD;
             the patient.&#xD;
&#xD;
          3. Participant has received a SARS-COV-2 vaccine within the prior 30 days&#xD;
&#xD;
          4. Known previous history of serious allergic reaction to blood product transfusion,&#xD;
             intravenous immunoglobulin or other injectable form of IgG will exclude a patient from&#xD;
             hyperimmune globulin&#xD;
&#xD;
          5. Known personal or religious objections to receiving blood products will exclude a&#xD;
             patient from hyperimmune globulin&#xD;
&#xD;
          6. Pregnant or breastfeeding female participants will be excluded from hyperimmune&#xD;
             globulin&#xD;
&#xD;
          7. Prior history of a thrombotic event (including acute coronary syndromes,&#xD;
             cerebrovascular syndromes, pulmonary or deep vein thrombosis) within the prior 30 days&#xD;
             of randomisation will exclude a patient from receiving hyperimmune globulin&#xD;
&#xD;
          8. Having a creatinine clearance of less than 50mL/min will exclude a patient from&#xD;
             receiving hyperimmune globulin&#xD;
&#xD;
        D. Domain C (Anticoagulation) domain-level exclusions:&#xD;
&#xD;
        Patients will be excluded from this domain if they have any of the following:&#xD;
&#xD;
          -  Receiving dual antiplatelet therapy&#xD;
&#xD;
          -  The treating clinician intends to continue or commence therapeutic anticoagulation&#xD;
&#xD;
          -  Contraindication to receiving low molecular weight heparin or unfractionated heparin,&#xD;
             including the known or suspected history of heparin-induced thrombocytopenia or other&#xD;
             adverse reaction to prior heparin exposure such as hypersensitivity&#xD;
&#xD;
          -  Severe thrombocytopenia (platelet count less than 530 x 109/L)&#xD;
&#xD;
          -  History of intracranial haemorrhage in the previous 3 months&#xD;
&#xD;
          -  Severe renal impairment, defined as estimated glomerular filtration rate less than&#xD;
             15ml/min/1.73m2&#xD;
&#xD;
          -  A current or recurrent condition with a high risk of major bleeding (e.g. bleeding&#xD;
             disorder), or a baseline coagulation profile (within the previous 3 days) that&#xD;
             indicates a high risk of bleeding, that would be considered a contraindication to&#xD;
             receive therapeutic anticoagulation&#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>Steven Tong, A/Prof</last_name>
    <role>Study Chair</role>
    <affiliation>Melbourne Health</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Grace McPhee</last_name>
    <phone>+61 3 8344 3276</phone>
    <email>grace.mcphee@unimelb.edu.au</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jocelyn Mora</last_name>
    <phone>+61 3 8344 0770</phone>
    <email>jocelyn.mora@unimelb.edu.au</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Calvary Public Bruce Hospital</name>
      <address>
        <city>Bruce</city>
        <state>Australian Capital Territory</state>
        <zip>2617</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Chong-Wei Ong</last_name>
      <email>chong-wei.ong@act.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Canberra Hospital</name>
      <address>
        <city>Canberra</city>
        <state>Australian Capital Territory</state>
        <zip>2605</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Sanjaya Senanayake, A/Prof</last_name>
      <email>sanjaya.senanayake@act.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Armidale Hospital</name>
      <address>
        <city>Armidale</city>
        <state>New South Wales</state>
        <zip>2350</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Bankstown-Lidcombe Hospital</name>
      <address>
        <city>Bankstown</city>
        <state>New South Wales</state>
        <zip>2200</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Ravindra Dotel</last_name>
      <email>Ravindra.Dotel@health.nsw.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Blacktown Hospital</name>
      <address>
        <city>Blacktown</city>
        <state>New South Wales</state>
        <zip>2148</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Ravindra Dotel, Dr</last_name>
      <email>Ravindra.Dotel@health.nsw.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Campbelltown Hospital</name>
      <address>
        <city>Campbelltown</city>
        <state>New South Wales</state>
        <zip>2560</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Belinda Cochrane</last_name>
      <email>belindacochrane@bigpond.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Prince Alfred Hospital</name>
      <address>
        <city>Camperdown</city>
        <state>New South Wales</state>
        <zip>2050</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Sebastian van Hal, A/Prof</last_name>
      <email>Sebastiaan.vanhal@health.nsw.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Sutherland Hospital</name>
      <address>
        <city>Caringbah</city>
        <state>New South Wales</state>
        <zip>2229</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Robert Stevens, Dr</last_name>
      <email>Robert.Stevens@health.nsw.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Coffs Harbour Health Campus</name>
      <address>
        <city>Coffs Harbour</city>
        <state>New South Wales</state>
        <zip>2450</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Christiaan Mostert</last_name>
      <email>Christiaan.Mostert@health.nsw.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>St Vincent's Hospital Sydney</name>
      <address>
        <city>Darlinghurst</city>
        <state>New South Wales</state>
        <zip>2010</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gail Matthews</last_name>
      <email>Gmatthews@kirby.unsw.edu.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Northern Beaches Hospital</name>
      <address>
        <city>Frenchs Forest</city>
        <state>New South Wales</state>
        <zip>2086</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Michael Mina</last_name>
      <email>michaelmina2001@yahoo.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Griffith Base Hospital</name>
      <address>
        <city>Griffith</city>
        <state>New South Wales</state>
        <zip>2680</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Hornsby Ku-Ring Gai Hospital</name>
      <address>
        <city>Hornsby</city>
        <state>New South Wales</state>
        <zip>2077</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Yuen Su, Dr</last_name>
      <email>yuensu@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Nepean Hospital</name>
      <address>
        <city>Kingswood</city>
        <state>New South Wales</state>
        <zip>2747</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Archana Sud, A/Prof</last_name>
      <email>Archana.Sud@health.nsw.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>St George Hospital</name>
      <address>
        <city>Kogarah</city>
        <state>New South Wales</state>
        <zip>2217</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Richard Sullivan, Dr</last_name>
      <email>richard.sullivan@health.nsw.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Liverpool Hospital</name>
      <address>
        <city>Liverpool</city>
        <state>New South Wales</state>
        <zip>2170</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hong Foo, Dr</last_name>
      <email>hong.foo@health.nsw.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>John Hunter Hospital</name>
      <address>
        <city>New Lambton Heights</city>
        <state>New South Wales</state>
        <zip>2305</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joshua Davies, Dr</last_name>
      <email>Joshua.Davies@menzies.edu.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Orange Health Service</name>
      <address>
        <city>Orange</city>
        <state>New South Wales</state>
        <zip>2800</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Port Macquarie Base Hospital</name>
      <address>
        <city>Port Macquarie</city>
        <state>New South Wales</state>
        <zip>2444</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nilar Lwin, Dr</last_name>
      <email>Nilarlwin83@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Prince of Wales Hospital</name>
      <address>
        <city>Randwick</city>
        <state>New South Wales</state>
        <zip>2031</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jeffrey Post, A/Prof</last_name>
      <email>Jeffrey.Post@health.nsw.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal North Shore Hospital</name>
      <address>
        <city>St Leonards</city>
        <state>New South Wales</state>
        <zip>2065</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Bernard Hudson</last_name>
      <email>bernard.hudson@health.nsw.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Tweed Hospital</name>
      <address>
        <city>Tweed Heads</city>
        <state>New South Wales</state>
        <zip>2485</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Alison Winning, Dr</last_name>
      <email>alison.winning@health.nsw.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Wagga Wagga Base Hospital</name>
      <address>
        <city>Wagga Wagga</city>
        <state>New South Wales</state>
        <zip>2650</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Timothy Gilbey</last_name>
      <email>timothy.gilbey@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Calvary Mater Newcastle</name>
      <address>
        <city>Waratah</city>
        <state>New South Wales</state>
        <zip>2298</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Paul Wilson, Dr</last_name>
      <email>paul.wilson@calvarymater.org.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Westmead Hospital</name>
      <address>
        <city>Westmead</city>
        <state>New South Wales</state>
        <zip>2145</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Matthew O'Sullivan, Dr</last_name>
      <email>matthew.osullivan@health.nsw.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Wollongong Hospital</name>
      <address>
        <city>Wollongong</city>
        <state>New South Wales</state>
        <zip>2500</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Omar Shum, Dr</last_name>
      <email>Omar.Shum@health.nsw.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Darwin Hospital</name>
      <address>
        <city>Tiwi</city>
        <state>Northern Territory</state>
        <zip>0810</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jane Davies, Dr</last_name>
      <email>jane.davies@menzies.edu.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sunshine Coast University Hospital</name>
      <address>
        <city>Birtinya</city>
        <state>Queensland</state>
        <zip>4575</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>The Prince Charles Hospital</name>
      <address>
        <city>Chermside</city>
        <state>Queensland</state>
        <zip>4032</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrew Burke, Dr</last_name>
      <email>Andrew.Burke@health.qld.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Brisbane and Women's Hospital</name>
      <address>
        <city>Herston</city>
        <state>Queensland</state>
        <zip>4120</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Adam Stewart, Dr</last_name>
      <email>Adam.Stewart@health.qld.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Gold Coast University Hospital</name>
      <address>
        <city>Southport</city>
        <state>Queensland</state>
        <zip>4215</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>John Gerrard</last_name>
      <email>John.Gerrard@health.qld.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Lyell McEwin Hospital</name>
      <address>
        <city>Elizabeth Vale</city>
        <state>South Australia</state>
        <zip>5112</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Mark Boyd, Prof</last_name>
      <email>mark.boyd@adelaide.edu.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Hobart Hospital</name>
      <address>
        <city>Hobart</city>
        <state>Tasmania</state>
        <zip>7000</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Alison Ratcliff, Dr</last_name>
      <email>alison.ratcliff@ths.tas.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Launceston General Hospital</name>
      <address>
        <city>Launceston</city>
        <state>Tasmania</state>
        <zip>7250</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Ballarat Health Services</name>
      <address>
        <city>Ballarat Central</city>
        <state>Victoria</state>
        <zip>3350</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rob Commons, Dr</last_name>
      <email>robert.commons@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>St John of God Ballarat Hospital</name>
      <address>
        <city>Ballarat</city>
        <state>Victoria</state>
        <zip>3350</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Rob Commons, Dr</last_name>
      <email>robert.commons@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Bendigo Health</name>
      <address>
        <city>Bendigo</city>
        <state>Victoria</state>
        <zip>3550</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Eastern Health (Box Hill Hospital)</name>
      <address>
        <city>Box Hill</city>
        <state>Victoria</state>
        <zip>3128</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Lyn-Li Lim, Dr</last_name>
      <email>LynLi.Lim@easternhealth.org.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Monash Health</name>
      <address>
        <city>Clayton</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Ben Rogers, Dr</last_name>
      <email>ben.rogers@monash.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Northern Health</name>
      <address>
        <city>Epping</city>
        <state>Victoria</state>
        <zip>3076</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Craig Aboltins, A/Prof</last_name>
      <email>Craig.Aboltins@nh.org.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>St. Vincent's Hospital Melbourne</name>
      <address>
        <city>Fitzroy</city>
        <state>Victoria</state>
        <zip>3065</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Frankston Hospital - Penninsula Health</name>
      <address>
        <city>Frankston</city>
        <state>Victoria</state>
        <zip>3199</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Peninsula Private Hospital</name>
      <address>
        <city>Frankston</city>
        <state>Victoria</state>
        <zip>3199</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>David Lister</last_name>
      <email>david.michael.lister@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Barwon Health - University Hospital Geelong</name>
      <address>
        <city>Geelong</city>
        <state>Victoria</state>
        <zip>3220</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Daniel O'Brien, A/Prof</last_name>
      <email>daniel.o'brien@barwonhealth.org.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Austin Health</name>
      <address>
        <city>Heidelberg</city>
        <state>Victoria</state>
        <zip>3084</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Patrick Charles, Dr</last_name>
      <email>patrick.charles@austin.org.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Cabrini Health</name>
      <address>
        <city>Malvern</city>
        <state>Victoria</state>
        <zip>3144</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>David Sheffield, Dr</last_name>
      <email>sheffield010@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Alfred Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3004</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>James McMahon, Dr</last_name>
      <email>james.mcmahon@monash.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Melbourne Hospital</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joseph Sasadeusz, A/Prof</last_name>
      <email>j.sasadeusz@mh.org.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Epworth Richmond</name>
      <address>
        <city>Richmond</city>
        <state>Victoria</state>
        <zip>3121</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Goulburn Valley Health</name>
      <address>
        <city>Shepparton</city>
        <state>Victoria</state>
        <zip>3630</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Thomas Schulz, Dr</last_name>
      <email>Thomas.Schulz@mh.org.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Western Health</name>
      <address>
        <city>St Albans</city>
        <state>Victoria</state>
        <zip>3021</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>James Molton, Dr</last_name>
      <email>james.molton@wh.org.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Latrobe Regional Hospital</name>
      <address>
        <city>Traralgon</city>
        <state>Victoria</state>
        <zip>3844</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>West Gippsland Hospital</name>
      <address>
        <city>Warragul</city>
        <state>Victoria</state>
        <zip>3820</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Alex Ctai, Dr</last_name>
      <email>alexyctai@gmail.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Albury Wodonga Health</name>
      <address>
        <city>Wodonga</city>
        <state>Victoria</state>
        <zip>3690</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Rockingham General Hospital</name>
      <address>
        <city>Cooloongup</city>
        <state>Western Australia</state>
        <zip>6168</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Joondalup Health Campus</name>
      <address>
        <city>Joondalup</city>
        <state>Western Australia</state>
        <zip>6027</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jonathan Chambers</last_name>
      <email>Jonathan.Chambers@wdp.com.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Armadale Health Service</name>
      <address>
        <city>Mount Nasura</city>
        <state>Western Australia</state>
        <zip>6112</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Fiona Stanley Hospita</name>
      <address>
        <city>Murdoch</city>
        <state>Western Australia</state>
        <zip>6150</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Edward Raby, Dr</last_name>
      <email>Edward.Raby@health.wa.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sir Charles Gairdner Hospital</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Julie Hart, Dr</last_name>
      <email>Julie.hart@health.wa.gov</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Perth Hospital</name>
      <address>
        <city>Perth</city>
        <state>Western Australia</state>
        <zip>6000</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Owen Robinson, A/Prof</last_name>
      <email>Owen.Robinson@health.wa.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>St John of God Subiaco Hospital</name>
      <address>
        <city>Subiaco</city>
        <state>Western Australia</state>
        <zip>6008</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>January 6, 2023</last_update_submitted>
  <last_update_submitted_qc>January 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Melbourne</investigator_affiliation>
    <investigator_full_name>Associate Professor Steven Tong</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nafamostat</mesh_term>
    <mesh_term>Enoxaparin</mesh_term>
    <mesh_term>Dalteparin</mesh_term>
    <mesh_term>Tinzaparin</mesh_term>
    <mesh_term>Heparin, Low-Molecular-Weight</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04483960
org study id: ERM 62646-A
nct id: NCT04483960
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
An International Multi-Centre Randomised Adaptive Platform Clinical Trial to Assess the
      Clinical, Virological and Immunological Outcomes in Patients with SARS-CoV-2 Infection
      (COVID-19).
ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled adaptive
      platform trial. The study design will allow harmonisation with existing frameworks such as
      the Sentinel Travellers Research Preparedness Platform for Emerging Infectious Diseases
      (SETREP-ID) and the Randomised, embedded, multifactorial adaptive platform trial for
      community acquired pneumonia (REMAP-CAP) study.

      Platform trials allow multiple questions to be evaluated simultaneously and sequentially
      within the platform, and evaluate interaction between different treatment options, to achieve
      the goal of determining the optimal combination of treatments for the disease as rapidly as
      possible. The overarching objective of ASCOT-ADAPT is to identify the regimen (combination of
      interventions) associated with the highest chance of survival free of advanced respiratory
      support or vasopressor / inotropic support at 28 days after randomisation, in adults
      hospitalised with COVID-19 but not requiring ICU-level care at baseline.

      In the initial implementation of the adaptive platform, recruiting sites have the option to
      participate in one or more of three treatment domains. Consented participants will then be
      able to choose whether to be enrolled into one or more available domains concurrently.
      Participants will then be randomised to the corresponding interventions:

      Intervention domain A (antiviral):

      Participants will be randomised using response adaptive randomisation (RAR) on day 1 to
      receive either i) standard of care without nafamostat; or ii) standard of care with
      nafamostat

      (Domain Closed) Intervention domain B (antibody): Participants will be randomised using
      response adaptive randomisation (RAR) on day 1 to receive either i) standard of care without
      hyperimmune globulin; or ii) standard of care with hyperimmune globulin

      (Domain Closed) Intervention domain C (anticoagulation): Participants will be randomised
      using response adaptive randomisation (RAR) on day 1 to receive either i) standard dose
      thromboprophylaxis; or ii) intermediate dose thromboprophylaxis; or iii) therapeutic
      anticoagulation

      Daily data will be collected for the first 28 days or until discharge, whichever is earlier.
      There will be a core dataset collected for all patients at all sites and enhanced and
      research data and biological samples for sites with capacity. Participants will be followed
      up at Day 90.
allocation: Randomized
intervention model: Factorial Assignment
intervention model description: Participants enrolled into the study have the option of deciding whether to be randomised in one or more (if available) treatment domains concurrently, if they meet the eligibility criteria.
primary purpose: Treatment
masking: None (Open Label)
masking description: This is an open-label study.
measure: Death from any cause or requirement of new intensive respiratory support (invasive or non-invasive ventilation) or vasopressor/inotropic support.
time frame: 28 days
description: This includes any participant who receives non-invasive mechanical ventilation (either CPAP or BIPAP, apart from the below considerations) any time after enrolment even if not transferred to ICU. It does NOT include the use of humidified high-flow nasal prong oxygen.
Participants on pre-existing home BiPAP or CPAP will not be considered to have met the primary outcome unless they have either i. required invasive mechanical ventilation (i.e. intubation), or ii. graduated from CPAP only whilst asleep to BiPAP at any time, or iii. graduated from BiPAP only whilst asleep to BiPAP for >12 hours/day, or iv. died by day 28
measure: Time to clinical recovery
time frame: 28 days
description: Defined as the first day, during the 28 days after enrolment, on which a patient satisfies categories 1, 2, or 3 on the WHO eight-point ordinal outcome scale. For the purposes of this outcome measure, it will be assumed that the participant is not hospitalised on the first day following discharge.
measure: WHO 8-point ordinal outcome scale
time frame: 28 days
description: The ordinal score is:
Not hospitalised, no limitations on activities
Not hospitalised, limitation on activities
Hospitalised, not requiring supplemental oxygen and no longer requiring ongoing medical care (used if hospitalization was extended for infection control purposes)
Hospitalised, not requiring supplemental oxygen but requiring ongoing medical care (COVID-19 related or other medical conditions)
Hospitalised, requiring supplemental oxygen
Hospitalised, on non-invasive ventilation or high flow oxygen devices
Hospitalised, on invasive mechanical ventilation or ECMO
Death.
Admission to a Hospital in the Home unit is not counted as hospitalisation for the purposes of this ordinal scale. Patients who have been admitted to hospital and transferred to a Hospital in the Home unit will be assessed as either ordinal score 1 or 2.
measure: All-cause mortality
time frame: 28 days and 90 days
description: All-cause mortality
measure: Days alive and free of hospital
time frame: 28 days
description: Number of days
Days spent in a Hospital in the Home unit will not be counted as days in hospital as hospital means 'acute-care hospital' for the purposes of this endpoint.
measure: Days alive and free of invasive or non-invasive ventilation
time frame: 28 days
description: Number of days
measure: Shortness of breath
time frame: 28 days and 90 days
description: Patient reported outcome.
Dichotomous comparison of a subjective measure of shortness of breath such as: "Are you currently experiencing shortness of breath that you didn't have before you got COVID, or which is worse now than before you got COVID?"
Ordinal comparison of the modified Medical Research Council (mMRC) breathlessness scale:
Modified Medical Research Council (mMRC) Dyspnoea Scale for grading the severity of breathlessness during daily activities:
0 - I only get breathless with strenuous exercise
- I get short of breath when hurrying on level ground or walking up a slight hill
- On level ground, I walk slower than people of the same age because of breathlessness, or I have to stop for breath when walking at my own pace on the level
- I stop for breath after walking about 100 metres or after a few minutes on level ground
- I am too breathless to leave the house or I am breathless when dressing or undressing
measure: Quality of life
time frame: 28 days and 90 days
description: Measured by the EQ-5D-5L questionnaire
measure: Antiviral domain-specific outcome: Viral clearance
time frame: 3 and 7 days
description: Proportion of patients with negative SARS-CoV-2 RT-PCR from upper or lower respiratory tract samples, for those with results available.
measure: Antiviral domain-specific outcome: Viral load
time frame: 3 and 7 days
description: Changes in cycle threshold value in RT-PCR for SARS-CoV-2 from baseline to day 3 and from baseline to day 7, for those with results available from the same respiratory tract sample type.
measure: Antiviral domain-specific outcome: Safety (Liver enzymes)
time frame: Up to day 28 or day of discharge from hospital, whichever is earlier
description: o Elevation of Alanine Transaminase (ALT) or Aspartate Transaminase (AST) to >5x upper limit of normal
measure: Antiviral domain-specific outcome: Safety (potassium)
time frame: Up to day 28 or day of discharge from hospital, whichever is earlier
description: o Elevation of serum potassium to >5.5 mmol/L
measure: Antiviral domain-specific outcome: Safety (sodium)
time frame: Up to day 28 or day of discharge from hospital, whichever is earlier
description: o Decrease of serum sodium to <125 mmol/L
measure: Antiviral domain-specific outcome: Safety (bleeding)
time frame: Up to day 28 or day of discharge from hospital, whichever is earlier
description: o Major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH).
measure: Antiviral domain-specific outcome: Safety (thrombophlebitis)
time frame: Up to day 28 or day of discharge from hospital, whichever is earlier
description: o Thrombophlebitis/vasculitis at IV line site
measure: Antiviral domain-specific outcome: serious adverse reactions
time frame: 28 days
description: Any safety event that, in the judgment of the investigator, is both serious and either possibly, probably or definitely related to the study intervention(s).
measure: Anticoagulation domain-specific outcome: Confirmed deep venous thrombosis
time frame: 28 days
description: Yes/No
measure: Anticoagulation domain-specific outcome: Confirmed pulmonary embolus
time frame: 28 days
description: Yes/No
measure: Anticoagulation domain-specific outcome: Confirmed acute myocardial infarction
time frame: 28 days
description: Yes/No
measure: Anticoagulation domain-specific outcome: Confirmed ischemic cerebrovascular event
time frame: 28 days
description: Yes/No
measure: Anticoagulation domain-specific outcome: Major bleeding
time frame: 28 days
description: Yes/No - As defined by International Society on Thrombosis and Haemostasis (ISTH). Site of bleeding and which of the ISTH criteria are met will be recorded.
measure: Anticoagulation domain-specific outcome: Clinically relevant non-major bleeding
time frame: 28 days
description: Yes/No - As defined by International Society on Thrombosis and Haemostasis (ISTH).
measure: Anticoagulation domain-specific outcome: Heparin-induced thrombocytopenia (HIT)
time frame: 28 days
description: Yes/No - During index hospitalisation
measure: Anticoagulation domain-specific outcome: Other confirmed thrombotic event
time frame: 28 days
description: Yes/No - During index hospitalisation
measure: Antibody domain-specific outcome: Serious treatment-related adverse events
time frame: Within 24 hours of treatment
description: Including:
Serious allergic reaction or anaphylaxis
Transfusion-related acute lung injury (TRALI)
measure: Antibody domain-specific outcome: Haemolysis
time frame: Within 72 hours of last transfusion
description: Yes/No
measure: Antibody domain-specific outcome: Confirmed arterial thrombosis
time frame: 28 days
description: Yes/No - acute myocardial infarction, ischaemic cerebrovascular event, other
measure: Antibody domain-specific outcome: Confirmed venous thrombosis
time frame: 28 days
description: Yes/No - deep vein thrombosis, pulmonary embolus, other
arm group label: Antiviral - Standard of care
arm group type: No Intervention
description: Standard of care without nafamostat mesilate
arm group label: Antiviral - nafamostat mesilate
arm group type: Experimental
description: Nafamostat continuous IV infusion for 7 days or until day of hospital discharge at a dose of 0.2mg/kg/hour. No adjustment in dose is needed for renal impairment, including for renal dialysis. The daily dose of nafamostat should be administered in 500 mL (rate of infusion 20.8 mL/hour) of normal saline. Normal saline is recommended (due to the tendency for patients with COVID-19 towards hyponatraemia) but not mandated, and 5% dextrose would be acceptable if felt clinically appropriate.
arm group label: (Arm Closed) Anticoagulation - standard dose thromboprophylaxis
arm group type: Active Comparator
description: Patients will be administered a standard thromboprophylactic dose of low molecular weight heparin, choice of agent according to availability and local practice at the participating site.
arm group label: (Arm Closed) Anticoagulation - intermediate dose thromboprophylaxis
arm group type: Experimental
description: Patients will be administered an intermediate dose of low molecular weight heparin, choice of agent according to availability and local practice at the participating site. The maximum dose of enoxaparin will be 120 mg/d, tinzaparin 125 IU/kg/day (not available within Australia), and Dalteparin 15,000 IU/d.
arm group label: (Arm Closed) Anticoagulation - therapeutic anticoagulation
arm group type: Experimental
description: Therapeutic anticoagulation administered with LMWH daily until hospital discharge, admission to ICU or for a maximum of 28 days from randomisation. Choice of LMWH according to availability and local practice at the participating site
arm group label: (Arm Closed) Antibody - Standard of Care
arm group type: No Intervention
description: No hyperimmune globulin
arm group label: (Arm Closed) Antibody - hyperimmune globulin
arm group type: Experimental
description: 2 doses of 30mL (3x10mL vials) of COVID-19 Hyper-Immunoglobulin (Human) given over 2 days within 48 hours of randomisation
intervention type: Drug
intervention name: Nafamostat Mesilate
description: Nafamostat continuous IV infusion for 7 days or until day of hospital discharge at a dose of 0.2mg/kg/hour. No adjustment in dose is needed for renal impairment, including for renal dialysis. The daily dose of nafamostat should be administered in 500 mL (rate of infusion 20.8 mL/hour) of normal saline. Normal saline is recommended (due to the tendency for patients with COVID-19 towards hyponatraemia) but not mandated, and 5% dextrose would be acceptable if felt clinically appropriate.
arm group label: Antiviral - nafamostat mesilate
other name: Nafabelltan
intervention type: Drug
intervention name: Enoxaparin
description: Patients will be administered either a standard dose, intermediate dose or therapeutic anticoagulation of low molecular weight heparin (depending on assigned arm), choice of agent according to availability and local practice at the participating site.
The maximum dose of Enoxaparin will be 1mg/kg q12h or 1.5mg/kg q24h.
arm group label: (Arm Closed) Anticoagulation - intermediate dose thromboprophylaxis
arm group label: (Arm Closed) Anticoagulation - standard dose thromboprophylaxis
arm group label: (Arm Closed) Anticoagulation - therapeutic anticoagulation
intervention type: Drug
intervention name: Dalteparin
description: Patients will be administered either a standard dose, intermediate dose or therapeutic anticoagulation of low molecular weight heparin (depending on assigned arm), choice of agent according to availability and local practice at the participating site.
The maximum dose of Dalteparin will be 100IU/kg q12h or 200IU/kg q24h.
arm group label: (Arm Closed) Anticoagulation - intermediate dose thromboprophylaxis
arm group label: (Arm Closed) Anticoagulation - standard dose thromboprophylaxis
arm group label: (Arm Closed) Anticoagulation - therapeutic anticoagulation
intervention type: Drug
intervention name: Tinzaparin
description: Patients will be administered either a standard dose, intermediate dose or therapeutic anticoagulation of low molecular weight heparin (depending on assigned arm), choice of agent according to availability and local practice at the participating site.
The maximum dose of Tinzaparin will be 175IU/kg q24h (not available within Australia).
arm group label: (Arm Closed) Anticoagulation - intermediate dose thromboprophylaxis
arm group label: (Arm Closed) Anticoagulation - standard dose thromboprophylaxis
arm group label: (Arm Closed) Anticoagulation - therapeutic anticoagulation
intervention type: Biological
intervention name: Hyperimmune globulin
description: 2 doses of 30mL (3x10mL vials) of COVID-19 Hyper-Immunoglobulin (Human) given over 2 days within 48 hours of randomisation. Three vials will have approximately 10500 AU of neutralising antibodies, equivalent to approximately 200mL of convalescent plasma
arm group label: (Arm Closed) Antibody - hyperimmune globulin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Steven Tong, A/Prof
role: Study Chair
affiliation: Melbourne Health
last name: Grace McPhee
phone: +61 3 8344 3276
email: grace.mcphee@unimelb.edu.au
last name: Jocelyn Mora
phone: +61 3 8344 0770
email: jocelyn.mora@unimelb.edu.au
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Withdrawn
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Withdrawn
country: Australia
responsible party type: Principal Investigator
investigator affiliation: University of Melbourne
investigator full name: Associate Professor Steven Tong
investigator title: Associate Professor
mesh term: Infections
mesh term: COVID-19
mesh term: Nafamostat
mesh term: Enoxaparin
mesh term: Dalteparin
mesh term: Tinzaparin
mesh term: Heparin, Low-Molecular-Weight