<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/NCT04408235</url>
  </required_header>
  <id_info>
    <org_study_id>EudraCT N°: 2020-001972-13</org_study_id>
    <nct_id>NCT04408235</nct_id>
  </id_info>
  <brief_title>High Versus Low LMWH Dosages in Hospitalized Patients With Severe COVID-19 Pneumonia and Coagulopathy</brief_title>
  <acronym>COVID-19 HD</acronym>
  <official_title>Randomised Controlled Trial Comparing High Versus Low LMWH Dosages in Hospitalized Patients With Severe COVID-19 Pneumonia and Coagulopathy Not Requiring Invasive Mechanical Ventilation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azienda Ospedaliero-Universitaria di Modena</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Azienda Ospedaliero-Universitaria di Modena</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>
      Randomized, controlled study conducted in hospitalized patients with severe COViD-19&#xD;
      pneumonia and coagulopathy not requiring invasive mechanical ventilation.&#xD;
&#xD;
      Aim of this study is to assess whether high doses of Low Molecular Weight Heparin (LMWH) (ie.&#xD;
      Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (ie, Enoxaparin 4000&#xD;
      IU once day) are:&#xD;
&#xD;
        1. More effective to prevent clinical worsening, defined as the occurrence of at least one&#xD;
           of the following events, whichever comes first, during hospital stay:&#xD;
&#xD;
             1. Death&#xD;
&#xD;
             2. Acute Myocardial Infarction [AMI]&#xD;
&#xD;
             3. Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]&#xD;
&#xD;
             4. Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or&#xD;
                Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients&#xD;
                who are in standard oxygen therapy by delivery interfaces at randomisation&#xD;
&#xD;
             5. Need for invasive mechanical ventilation for patients who are in non-invasive&#xD;
                mechanical ventilation at randomisation&#xD;
&#xD;
        2. Similar in terms of major bleeding risk during hospital stay&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicentre, randomised controlled, open label, investigator sponsored, two arms&#xD;
      study.&#xD;
&#xD;
      The study will involve 7 Italian Academic and non-Academic Internal Medicine Units, 2&#xD;
      Infectious Diseases Units, 1 Respiratory Diseases Unit.&#xD;
&#xD;
      Patients who satisfy all inclusion criteria and do not have any exclusion criteria and have&#xD;
      signed written informed consent, will be randomly assigned to a Low-Dose LMWH group (Control&#xD;
      Group) or High-Dose LMWH group (Intervention Group) in a 1:1 ratio.&#xD;
&#xD;
      Control Group (Low-Dose LMWH): patients in this group will be administered Enoxaparin&#xD;
      (Inhixa®) at standard prophylactic dose (i.e., 4000 IU subcutaneously once day).&#xD;
&#xD;
      Intervention Group (High-Dose LMWH): patients in this group will be administered Enoxaparin&#xD;
      (Inhixa®) at dose of 70 IU/kg every 12 hours, as reported in the following table.&#xD;
&#xD;
      The study is conceived as open-label: patients and all health-care personnel involved in the&#xD;
      study will be aware of the assigned group.&#xD;
&#xD;
      The treatments will be initiated as soon as possible after randomization (maximum allowed&#xD;
      starting time 12h after randomization).&#xD;
&#xD;
      Patients allocated to the two arms will maintain the doses of Enoxaparin, as stated in the&#xD;
      protocol, until:&#xD;
&#xD;
        1. hospital discharge or&#xD;
&#xD;
        2. when at least one of the following events occurs:&#xD;
&#xD;
             1. Acute Myocardial Infarction [AMI]&#xD;
&#xD;
             2. Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]&#xD;
&#xD;
             3. Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or&#xD;
                Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients,&#xD;
                who are in standard oxygen therapy by delivery interfaces at randomisation&#xD;
&#xD;
             4. Need for invasive mechanical ventilation for patients, who are in non-invasive&#xD;
                mechanical ventilation at randomisation&#xD;
&#xD;
             5. Major bleeding&#xD;
&#xD;
             6. Any adverse events and clinical condition requiring interruption of the scheduled&#xD;
                intervention according to the judgement of the physician in charge&#xD;
&#xD;
             7. Death&#xD;
&#xD;
      The decision about what type and dose of antithrombotic treatment to administer, after the&#xD;
      interruption of assigned dose of Enoxaparin, will be left to clinical judgement of the&#xD;
      physicians in charge.&#xD;
&#xD;
      Any information about the type and dose of antithrombotic treatments administered after the&#xD;
      interruption of the assigned dose of Enoxaparin will be collected until the hospital&#xD;
      discharge or death.&#xD;
&#xD;
      Each patient will be followed-up until hospital discharge. Information about the status&#xD;
      (dead/alive) of patients who are discharged from hospital before 30 days will be sought on&#xD;
      Day 30 from randomisation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">June 2020</start_date>
  <completion_date type="Anticipated">June 2021</completion_date>
  <primary_completion_date type="Anticipated">June 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 is a multicentre, randomised controlled, open label, investigator sponsored, two arms study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
    <masking_description>Randomisation will be centrally performed by using a secure, web-based system, which will be developed by the Methodological and Statistical Unit at the Azienda Ospedaliero-Universitaria of Modena. Randomisation stratified by 4 factors: 1) Gender (M/F); 2) Age (&lt;75/≥75 years); 3) BMI (&lt;30/≥30); 4) Co-morbidities (0-1/&gt;2) with random variable block sizes will be generated by STATA software. The web-based system will guarantee the allocation concealment.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first:</measure>
    <time_frame>through study completion, up to 30 days</time_frame>
    <description>Death&#xD;
Acute Myocardial Infarction [AMI]&#xD;
Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]&#xD;
Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients, who are in standard oxygen therapy by delivery interfaces at randomisation&#xD;
Need for invasive mechanical ventilation for patients, who are in non-invasive mechanical ventilation at randomisation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Any of the following events occurring within the hospital stay</measure>
    <time_frame>through study completion, up to 30 days</time_frame>
    <description>Death&#xD;
Acute Myocardial Infarction [AMI]&#xD;
Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]&#xD;
Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients, who are in standard oxygen therapy by delivery interfaces at randomisation&#xD;
Need for invasive mechanical ventilation for patients, who are in non-invasive mechanical ventilation at randomisation&#xD;
Improvement of laboratory parameters of disease severity, including:&#xD;
D-dimer level&#xD;
Plasma fibrinogen levels&#xD;
Mean Platelet Volume&#xD;
Lymphocyte/Neutrophil ratio&#xD;
IL-6 plasma levels</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality at 30 days</measure>
    <time_frame>30 days</time_frame>
    <description>Information about patients' status will be sought in those who are discharged before 30 days on Day 30 from randomisation.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>COVID</condition>
  <condition>Pneumonia, Viral</condition>
  <condition>Coagulation Disorder</condition>
  <arm_group>
    <arm_group_label>Low-Dose LMWH</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Enoxaparin 4000 IU daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High-Dose LMWH</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Enoxaparin 70 IU/kg twice daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enoxaparin</intervention_name>
    <description>Low-Dose LMWH: enoxaparin 4000 IU daily; High dose LMWH: 70 IU/kg twice daily</description>
    <arm_group_label>High-Dose LMWH</arm_group_label>
    <arm_group_label>Low-Dose LMWH</arm_group_label>
    <other_name>Inhixa®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria (all required):&#xD;
&#xD;
          -  Positive SARS-CoV-2 diagnostic (on pharyngeal swab of deep airways material)&#xD;
&#xD;
          -  Severe pneumonia defined by the presence of at least one of the following criteria:&#xD;
&#xD;
               1. Respiratory Rate ≥25 breaths /min&#xD;
&#xD;
               2. Arterial oxygen saturation≤93% at rest on ambient air&#xD;
&#xD;
               3. PaO2/FiO2 ≤300 mmHg&#xD;
&#xD;
          -  Coagulopathy, defined by the presence of at least one of the following criteria:&#xD;
&#xD;
               1. D-dimer &gt;4 times the upper level of normal reference range&#xD;
&#xD;
               2. Sepsis-Induced Coagulopathy (SIC) score &gt;4&#xD;
&#xD;
          -  No need for invasive mechanical ventilation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Invasive mechanical ventilation&#xD;
&#xD;
          -  Thrombocytopenia (platelet count &lt; 80.000 mm3)&#xD;
&#xD;
          -  Coagulopathy: INR &gt;1.5, aPTT ratio &gt; 1.4&#xD;
&#xD;
          -  Impaired renal function (eGFR calculated by CKD-EPI Creatinine equation &lt; 30 ml/min)&#xD;
&#xD;
          -  Known hypersensitivity to enoxaparin&#xD;
&#xD;
          -  History of heparin induced thrombocytopenia&#xD;
&#xD;
          -  Presence of an active bleeding or a pathology susceptible of bleeding in presence of&#xD;
             anticoagulation (e.g. recent haemorrhagic stroke, peptic ulcer, malignant cancer at&#xD;
             high risk of haemorrhage, recent neurosurgery or ophthalmic surgery, vascular&#xD;
             aneurysms, arteriovenous malformations)&#xD;
&#xD;
          -  Concomitant anticoagulant treatment for other indications (e.g. atrial fibrillation,&#xD;
             venous thromboembolism, prosthetic heart valves).&#xD;
&#xD;
          -  Concomitant double antiplatelet therapy&#xD;
&#xD;
          -  Administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin&#xD;
             (UFH) for more than 72 hours before randomization; prophylactic doses are allowed&#xD;
&#xD;
          -  Pregnancy or breastfeeding or positive pregnancy test&#xD;
&#xD;
          -  Presence of other severe diseases impairing life expectancy (e.g. patients are not&#xD;
             expected to survive 28 days given their pre-existing medical condition)&#xD;
&#xD;
          -  Lack or withdrawal of informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marco Marietta, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Azienda Ospedaliero-Universitaria di Modena</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Marco Marietta, MD</last_name>
    <phone>0594224640</phone>
    <phone_ext>+39</phone_ext>
    <email>marco.marietta@unimore.it</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Pasquale Mighali</last_name>
    <phone>0594225868</phone>
    <phone_ext>+39</phone_ext>
    <email>mighali.pasquale@aou.mo.it</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria</name>
      <address>
        <city>Modena</city>
        <zip>41124</zip>
        <country>Italy</country>
      </address>
    </facility>
    <contact>
      <last_name>Pasquale Mighali</last_name>
      <phone>0594225868</phone>
      <phone_ext>+39</phone_ext>
      <email>mighali.pasquale@policlinico.mo.it</email>
    </contact>
    <investigator>
      <last_name>Marco Marietta, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <reference>
    <citation>Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934-943. doi: 10.1001/jamainternmed.2020.0994. Erratum In: JAMA Intern Med. 2020 Jul 1;180(7):1031.</citation>
    <PMID>32167524</PMID>
  </reference>
  <reference>
    <citation>Leisman DE, Deutschman CS, Legrand M. Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation. Intensive Care Med. 2020 Jun;46(6):1105-1108. doi: 10.1007/s00134-020-06059-6. Epub 2020 Apr 28. No abstract available.</citation>
    <PMID>32347323</PMID>
  </reference>
  <reference>
    <citation>Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020 May;18(5):1094-1099. doi: 10.1111/jth.14817. Epub 2020 Apr 27.</citation>
    <PMID>32220112</PMID>
  </reference>
  <reference>
    <citation>Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr;18(4):844-847. doi: 10.1111/jth.14768. Epub 2020 Mar 13.</citation>
    <PMID>32073213</PMID>
  </reference>
  <reference>
    <citation>Marietta M, Ageno W, Artoni A, De Candia E, Gresele P, Marchetti M, Marcucci R, Tripodi A. COVID-19 and haemostasis: a position paper from Italian Society on Thrombosis and Haemostasis (SISET). Blood Transfus. 2020 May;18(3):167-169. doi: 10.2450/2020.0083-20. Epub 2020 Apr 8. No abstract available.</citation>
    <PMID>32281926</PMID>
  </reference>
  <reference>
    <citation>Thachil J, Tang N, Gando S, Falanga A, Cattaneo M, Levi M, Clark C, Iba T. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020 May;18(5):1023-1026. doi: 10.1111/jth.14810. Epub 2020 Apr 27. No abstract available.</citation>
    <PMID>32338827</PMID>
  </reference>
  <reference>
    <citation>Thachil J. The versatile heparin in COVID-19. J Thromb Haemost. 2020 May;18(5):1020-1022. doi: 10.1111/jth.14821. Epub 2020 Apr 27. No abstract available.</citation>
    <PMID>32239799</PMID>
  </reference>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 26, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>May 27, 2020</last_update_submitted>
  <last_update_submitted_qc>May 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Azienda Ospedaliero-Universitaria di Modena</investigator_affiliation>
    <investigator_full_name>Marco Marietta</investigator_full_name>
    <investigator_title>Head, Hemostasis and Thrombosis Unit</investigator_title>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>PNEUMONIA</keyword>
  <keyword>COAGULOPATHY</keyword>
  <keyword>LOW-MOLECULAR WEIGHT HEPARIN</keyword>
  <keyword>ENOXAPARIN</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Pneumonia, Viral</mesh_term>
    <mesh_term>Hemostatic Disorders</mesh_term>
    <mesh_term>Blood Coagulation Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Enoxaparin</mesh_term>
  </intervention_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/NCT04408235
org study id: EudraCT N°: 2020-001972-13
nct id: NCT04408235
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Randomized, controlled study conducted in hospitalized patients with severe COViD-19
      pneumonia and coagulopathy not requiring invasive mechanical ventilation.

      Aim of this study is to assess whether high doses of Low Molecular Weight Heparin (LMWH) (ie.
      Enoxaparin 70 IU/kg twice daily) compared to standard prophylactic dose (ie, Enoxaparin 4000
      IU once day) are:

        1. More effective to prevent clinical worsening, defined as the occurrence of at least one
           of the following events, whichever comes first, during hospital stay:

             1. Death

             2. Acute Myocardial Infarction [AMI]

             3. Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]

             4. Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or
                Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients
                who are in standard oxygen therapy by delivery interfaces at randomisation

             5. Need for invasive mechanical ventilation for patients who are in non-invasive
                mechanical ventilation at randomisation

        2. Similar in terms of major bleeding risk during hospital stay
This is a multicentre, randomised controlled, open label, investigator sponsored, two arms
      study.

      The study will involve 7 Italian Academic and non-Academic Internal Medicine Units, 2
      Infectious Diseases Units, 1 Respiratory Diseases Unit.

      Patients who satisfy all inclusion criteria and do not have any exclusion criteria and have
      signed written informed consent, will be randomly assigned to a Low-Dose LMWH group (Control
      Group) or High-Dose LMWH group (Intervention Group) in a 1:1 ratio.

      Control Group (Low-Dose LMWH): patients in this group will be administered Enoxaparin
      (Inhixa®) at standard prophylactic dose (i.e., 4000 IU subcutaneously once day).

      Intervention Group (High-Dose LMWH): patients in this group will be administered Enoxaparin
      (Inhixa®) at dose of 70 IU/kg every 12 hours, as reported in the following table.

      The study is conceived as open-label: patients and all health-care personnel involved in the
      study will be aware of the assigned group.

      The treatments will be initiated as soon as possible after randomization (maximum allowed
      starting time 12h after randomization).

      Patients allocated to the two arms will maintain the doses of Enoxaparin, as stated in the
      protocol, until:

        1. hospital discharge or

        2. when at least one of the following events occurs:

             1. Acute Myocardial Infarction [AMI]

             2. Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]

             3. Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or
                Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients,
                who are in standard oxygen therapy by delivery interfaces at randomisation

             4. Need for invasive mechanical ventilation for patients, who are in non-invasive
                mechanical ventilation at randomisation

             5. Major bleeding

             6. Any adverse events and clinical condition requiring interruption of the scheduled
                intervention according to the judgement of the physician in charge

             7. Death

      The decision about what type and dose of antithrombotic treatment to administer, after the
      interruption of assigned dose of Enoxaparin, will be left to clinical judgement of the
      physicians in charge.

      Any information about the type and dose of antithrombotic treatments administered after the
      interruption of the assigned dose of Enoxaparin will be collected until the hospital
      discharge or death.

      Each patient will be followed-up until hospital discharge. Information about the status
      (dead/alive) of patients who are discharged from hospital before 30 days will be sought on
      Day 30 from randomisation.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a multicentre, randomised controlled, open label, investigator sponsored, two arms study.
primary purpose: Treatment
masking: Single (Investigator)
masking description: Randomisation will be centrally performed by using a secure, web-based system, which will be developed by the Methodological and Statistical Unit at the Azienda Ospedaliero-Universitaria of Modena. Randomisation stratified by 4 factors: 1) Gender (M/F); 2) Age (<75/≥75 years); 3) BMI (<30/≥30); 4) Co-morbidities (0-1/>2) with random variable block sizes will be generated by STATA software. The web-based system will guarantee the allocation concealment.
measure: Clinical worsening, defined as the occurrence of at least one of the following events, whichever comes first:
time frame: through study completion, up to 30 days
description: Death
Acute Myocardial Infarction [AMI]
Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]
Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients, who are in standard oxygen therapy by delivery interfaces at randomisation
Need for invasive mechanical ventilation for patients, who are in non-invasive mechanical ventilation at randomisation
measure: Any of the following events occurring within the hospital stay
time frame: through study completion, up to 30 days
description: Death
Acute Myocardial Infarction [AMI]
Objectively confirmed, symptomatic arterial or venous thromboembolism [TE]
Need for either non-invasive - Continuous Positive Airway Pressure (Cpap) or Non-Invasive Ventilation (NIV) - or invasive mechanical ventilation for patients, who are in standard oxygen therapy by delivery interfaces at randomisation
Need for invasive mechanical ventilation for patients, who are in non-invasive mechanical ventilation at randomisation
Improvement of laboratory parameters of disease severity, including:
D-dimer level
Plasma fibrinogen levels
Mean Platelet Volume
Lymphocyte/Neutrophil ratio
IL-6 plasma levels
measure: Mortality at 30 days
time frame: 30 days
description: Information about patients' status will be sought in those who are discharged before 30 days on Day 30 from randomisation.
arm group label: Low-Dose LMWH
arm group type: Active Comparator
description: Enoxaparin 4000 IU daily
arm group label: High-Dose LMWH
arm group type: Experimental
description: Enoxaparin 70 IU/kg twice daily
intervention type: Drug
intervention name: Enoxaparin
description: Low-Dose LMWH: enoxaparin 4000 IU daily; High dose LMWH: 70 IU/kg twice daily
arm group label: High-Dose LMWH
arm group label: Low-Dose LMWH
other name: Inhixa®
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Marco Marietta, MD
role: Principal Investigator
affiliation: Azienda Ospedaliero-Universitaria di Modena
last name: Marco Marietta, MD
phone: 0594224640
phone ext: +39
email: marco.marietta@unimore.it
last name: Pasquale Mighali
phone: 0594225868
phone ext: +39
email: mighali.pasquale@aou.mo.it
facility: 
contact: 
investigator: 
country: Italy
citation: Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934-943. doi: 10.1001/jamainternmed.2020.0994. Erratum In: JAMA Intern Med. 2020 Jul 1;180(7):1031.
PMID: 32167524
citation: Leisman DE, Deutschman CS, Legrand M. Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation. Intensive Care Med. 2020 Jun;46(6):1105-1108. doi: 10.1007/s00134-020-06059-6. Epub 2020 Apr 28. No abstract available.
PMID: 32347323
citation: Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020 May;18(5):1094-1099. doi: 10.1111/jth.14817. Epub 2020 Apr 27.
PMID: 32220112
citation: Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr;18(4):844-847. doi: 10.1111/jth.14768. Epub 2020 Mar 13.
PMID: 32073213
citation: Marietta M, Ageno W, Artoni A, De Candia E, Gresele P, Marchetti M, Marcucci R, Tripodi A. COVID-19 and haemostasis: a position paper from Italian Society on Thrombosis and Haemostasis (SISET). Blood Transfus. 2020 May;18(3):167-169. doi: 10.2450/2020.0083-20. Epub 2020 Apr 8. No abstract available.
PMID: 32281926
citation: Thachil J, Tang N, Gando S, Falanga A, Cattaneo M, Levi M, Clark C, Iba T. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020 May;18(5):1023-1026. doi: 10.1111/jth.14810. Epub 2020 Apr 27. No abstract available.
PMID: 32338827
citation: Thachil J. The versatile heparin in COVID-19. J Thromb Haemost. 2020 May;18(5):1020-1022. doi: 10.1111/jth.14821. Epub 2020 Apr 27. No abstract available.
PMID: 32239799
responsible party type: Principal Investigator
investigator affiliation: Azienda Ospedaliero-Universitaria di Modena
investigator full name: Marco Marietta
investigator title: Head, Hemostasis and Thrombosis Unit
mesh term: COVID-19
mesh term: Pneumonia
mesh term: Pneumonia, Viral
mesh term: Hemostatic Disorders
mesh term: Blood Coagulation Disorders
mesh term: Enoxaparin
sharing ipd: No