<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/NCT04485429</url>
  </required_header>
  <id_info>
    <org_study_id>31180820600005249</org_study_id>
    <nct_id>NCT04485429</nct_id>
  </id_info>
  <brief_title>Efficacy Assessment of Methylprednisolone and Heparin in Patients With COVID-19 Pneumonia</brief_title>
  <official_title>Efficacy Assessment of Methylprednisolone and Heparin in Patients With COVID-19 Pneumonia: A Randomized, Controlled, 2x2 Factorial Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>D'Or Institute for Research and Education</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>D'Or Institute for Research and Education</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>
      The COVID-19 pandemic has been spreading continuously, and in Brazil, until July 19, 2020,&#xD;
      there have been more than 2,000,000 cases with more than 79,000 deaths, with daily increases.&#xD;
      The present study proposes to evaluate the efficacy of methylprednisolone and heparin in&#xD;
      treatment of patients with COVID-19 pneumonia in a randomized, controlled, 2x2 factorial&#xD;
      study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    It was not possible to perform the study due to the availability and logistics of porcine&#xD;
    heparin&#xD;
  </why_stopped>
  <start_date type="Actual">July 20, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2022</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of invasive mechanical ventilation</measure>
    <time_frame>28 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Severity assessment by ordinal severity scale</measure>
    <time_frame>3 days, 7 days, 14 days, 28 days after randomization</time_frame>
    <description>Severity assessment will be performed using the ordinal severity scale during hospitalization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity assessment by SOFA score</measure>
    <time_frame>3 days, 7 days, 14 days, 28 days after randomization</time_frame>
    <description>Severity assessment will be performed using the SOFA score during hospitalization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of stay in intensive care</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death rate</measure>
    <time_frame>14 days, 28 days, 60 days, 90 days after randomization</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Methylprednisolone + Standard treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive the standard treatment and methylprednisolone.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Full-dose heparin + Standard treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive the standard treatment and full-dose heparin,</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Methylprednisolone + Full-dose heparin + Standard treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive the standard treatment, methylprednisolone and full-dose heparin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Participants will receive the standard treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methylprednisolone</intervention_name>
    <description>Methylprednisolone 0.5 mg/kg every 12 hours intravenously for the first 14 days; followed by 0.5 mg/kg/day from day 15 to day 21; followed by 0.25mg/kg/day from day 22 to day 25; followed by 0.125 mg/kg/day, from day 26 to day 28 of treatment.</description>
    <arm_group_label>Methylprednisolone + Full-dose heparin + Standard treatment</arm_group_label>
    <arm_group_label>Methylprednisolone + Standard treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Heparin</intervention_name>
    <description>Enoxaparin 1 mg/kg subcutaneously every 12 hours (if creatinine clearance greater than 40ml/min) or Unfractionated heparin dosed to target activated partial thromboplastin time (aPTT) between 1.5 - 2.0 times the normal value (if creatinine clearance less or equal to 40ml/min). The treatment period with full-dose heparin will be 7 days. After 7 days of full-dose heparin, patients will continue using prophylactic dose of heparin, according to the standard treatment routine.</description>
    <arm_group_label>Full-dose heparin + Standard treatment</arm_group_label>
    <arm_group_label>Methylprednisolone + Full-dose heparin + Standard treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed diagnosis of COVID-19 by RT-PCR or serology with presence of IgM positive&#xD;
             antibodies;&#xD;
&#xD;
          -  Lung image (X-ray or chest CT) with involvement of at least 25% of the parenchyma;&#xD;
&#xD;
          -  O2 saturation in ambient air less than or equal to 93%&#xD;
&#xD;
          -  Alteration of inflammatory tests&#xD;
&#xD;
               -  D-Dimer above the reference value and&#xD;
&#xD;
               -  Elevation of C-reactive protein, ferritin or lactic dehydrogenase&#xD;
&#xD;
          -  Sign the consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  QT interval prolongation&#xD;
&#xD;
          -  Imminence of orotracheal intubation (intubation prediction in the first 4 hours after&#xD;
             randomization)&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding&#xD;
&#xD;
          -  Corticosteroid allergy or intolerance&#xD;
&#xD;
          -  Chronic corticosteroid users (prednisone equivalent &gt; 10 mg daily)&#xD;
&#xD;
          -  Patients diagnosed with cancer with increased bleeding potential&#xD;
&#xD;
          -  Patients in hemodialysis&#xD;
&#xD;
          -  History of peptic ulcer&#xD;
&#xD;
          -  Herpes zoster infection&#xD;
&#xD;
          -  History or active treatment of tuberculosis&#xD;
&#xD;
          -  Systemic fungal infection&#xD;
&#xD;
          -  Use of anticoagulation due to previous pathology&#xD;
&#xD;
          -  Glaucoma&#xD;
&#xD;
          -  Live virus vaccine up to 90 days before randomization&#xD;
&#xD;
          -  Known coagulopathy or thrombocytopenia (&lt;40,000/mm3) or hypofibrinogenemia (&lt; 50&#xD;
             mg/dL)&#xD;
&#xD;
          -  Recent bleeding&#xD;
&#xD;
          -  Another limiting comorbidity for administering the therapies provided for in this&#xD;
             protocol in in researcher's opinion&#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>Eduardo M Rego, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>D'Or Institute for Research and Education</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>D'Or Institute for Research and Education</name>
      <address>
        <city>Rio de Janeiro</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>July 23, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <last_update_submitted>August 4, 2021</last_update_submitted>
  <last_update_submitted_qc>August 4, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SARS-CoV-2</keyword>
  <keyword>Heparin</keyword>
  <keyword>Methylprednisolone</keyword>
  <keyword>Anticoagulation</keyword>
  <keyword>Coagulopathy</keyword>
  <keyword>Respiratory failure</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methylprednisolone</mesh_term>
    <mesh_term>Methylprednisolone Acetate</mesh_term>
    <mesh_term>Methylprednisolone Hemisuccinate</mesh_term>
    <mesh_term>Prednisolone</mesh_term>
    <mesh_term>Prednisolone acetate</mesh_term>
    <mesh_term>Heparin</mesh_term>
    <mesh_term>Prednisolone hemisuccinate</mesh_term>
    <mesh_term>Prednisolone phosphate</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/NCT04485429
org study id: 31180820600005249
nct id: NCT04485429
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The COVID-19 pandemic has been spreading continuously, and in Brazil, until July 19, 2020,
      there have been more than 2,000,000 cases with more than 79,000 deaths, with daily increases.
      The present study proposes to evaluate the efficacy of methylprednisolone and heparin in
      treatment of patients with COVID-19 pneumonia in a randomized, controlled, 2x2 factorial
      study.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of invasive mechanical ventilation
time frame: 28 days
measure: Severity assessment by ordinal severity scale
time frame: 3 days, 7 days, 14 days, 28 days after randomization
description: Severity assessment will be performed using the ordinal severity scale during hospitalization.
measure: Severity assessment by SOFA score
time frame: 3 days, 7 days, 14 days, 28 days after randomization
description: Severity assessment will be performed using the SOFA score during hospitalization.
measure: Length of hospital stay
time frame: 28 days
measure: Length of stay in intensive care
time frame: 28 days
measure: Death rate
time frame: 14 days, 28 days, 60 days, 90 days after randomization
arm group label: Methylprednisolone + Standard treatment
arm group type: Experimental
description: Participants will receive the standard treatment and methylprednisolone.
arm group label: Full-dose heparin + Standard treatment
arm group type: Experimental
description: Participants will receive the standard treatment and full-dose heparin,
arm group label: Methylprednisolone + Full-dose heparin + Standard treatment
arm group type: Experimental
description: Participants will receive the standard treatment, methylprednisolone and full-dose heparin
arm group label: Standard treatment
arm group type: No Intervention
description: Participants will receive the standard treatment
intervention type: Drug
intervention name: Methylprednisolone
description: Methylprednisolone 0.5 mg/kg every 12 hours intravenously for the first 14 days; followed by 0.5 mg/kg/day from day 15 to day 21; followed by 0.25mg/kg/day from day 22 to day 25; followed by 0.125 mg/kg/day, from day 26 to day 28 of treatment.
arm group label: Methylprednisolone + Full-dose heparin + Standard treatment
arm group label: Methylprednisolone + Standard treatment
intervention type: Drug
intervention name: Heparin
description: Enoxaparin 1 mg/kg subcutaneously every 12 hours (if creatinine clearance greater than 40ml/min) or Unfractionated heparin dosed to target activated partial thromboplastin time (aPTT) between 1.5 - 2.0 times the normal value (if creatinine clearance less or equal to 40ml/min). The treatment period with full-dose heparin will be 7 days. After 7 days of full-dose heparin, patients will continue using prophylactic dose of heparin, according to the standard treatment routine.
arm group label: Full-dose heparin + Standard treatment
arm group label: Methylprednisolone + Full-dose heparin + Standard treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Eduardo M Rego, MD, PhD
role: Principal Investigator
affiliation: D'Or Institute for Research and Education
facility: 
country: Brazil
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Pneumonia
mesh term: Methylprednisolone
mesh term: Methylprednisolone Acetate
mesh term: Methylprednisolone Hemisuccinate
mesh term: Prednisolone
mesh term: Prednisolone acetate
mesh term: Heparin
mesh term: Prednisolone hemisuccinate
mesh term: Prednisolone phosphate
sharing ipd: No