<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/NCT04422678</url>
  </required_header>
  <id_info>
    <org_study_id>Alex CCM 2020/5</org_study_id>
    <nct_id>NCT04422678</nct_id>
  </id_info>
  <brief_title>The Safety &amp; Efficacy of Imatinib for the Treatment of SARS-COV-2 Induced Pneumonia</brief_title>
  <official_title>Imatinib for the Treatment of SARS-COV-2 Induced Pneumonia: A Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alexandria University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Science, Technology &amp; Innovation Funding Authority (STIFA), Egypt</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Alexandria University</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>
      A randomized controlled pilot study on the safety &amp; efficacy of imatinib for the treatment of&#xD;
      patient with moderate to severe SARS-COV-2 induced pneumonia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      As the coronavirus disease (COVID-19) spreads worldwide, awaiting the development of a&#xD;
      vaccine, researchers are looking among the arsenal of available drugs, for a potential cure&#xD;
      or medication to improve patients' outcome. A highly elevated levels of cytokines in COVID-19&#xD;
      patients requiring ICU admission, has suggested that a &quot;cytokine storm&quot; was associated with&#xD;
      disease severity. Data from cellular, animal models and clinical trials, showed a beneficial&#xD;
      role of tyrosine kinase inhibitors in the regulation of inflammation, the maintenance of&#xD;
      endothelial barrier integrity, as well as the expression of antiviral properties. This data&#xD;
      is especially derived from imatinib, the most studied Abl family kinase inhibitor, that is&#xD;
      currently in clinical use for multiple medical conditions. Based on this encouraging data, we&#xD;
      hypothesize that imatinib might be beneficial for the treatment of patients with SARS-CoV-2&#xD;
      pneumonia, in the aim of preventing disease progression into the severe phenotype of hypoxic&#xD;
      respiratory failure and acute respiratory distress syndrome.&#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">October 2020</completion_date>
  <primary_completion_date type="Anticipated">September 2020</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Primary endpoint: Disease Progression</measure>
    <time_frame>30 Days</time_frame>
    <description>Proportion of patients with COVID-19 pneumonia progressed to critical illness in need for invasive mechanical ventilation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Improvement in Hypoxic Index</measure>
    <time_frame>From inclusion to 30 days follow up</time_frame>
    <description>Improvement of Hypoxic index( PaO2 / FiO2) calculated daily</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital Length of Stay</measure>
    <time_frame>From inclusion to 30 days follow up</time_frame>
    <description>Hospital Length of stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days on invasive mechanical ventilation</measure>
    <time_frame>From inclusion to 30 days follow up</time_frame>
    <description>Days on mechanical ventilation for patients needing intubation &amp; invasive mechanical ventilation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory Markers</measure>
    <time_frame>From inclusion to 30 days</time_frame>
    <description>Difference in the median levels of serum IL-6, serum ferritin, CRP at the end of the follow up period between all groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Viral clearance</measure>
    <time_frame>From inclusion to 30 days</time_frame>
    <description>Rate of viral clearance as monitored by SARS-COV-2 PCR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiological assessment</measure>
    <time_frame>From inclusion to 30 days</time_frame>
    <description>Difference in the overall evaluation of pulmonary infiltrative (improving / deteriorating) as assessed by imaging (Chest X-ray or Non-contrast pulmonary CT)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of Imatinib</measure>
    <time_frame>From inclusion to 60 days</time_frame>
    <description>Rate of serious adverse events (SAEs)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Imatinib Standard Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Imatinib 400 mg oral tablet once daily for 21 days&#xD;
In addition for the treatment for COVID-19 pneumonia according to the Egyptian National Protocol by the Ministry of Health (MOH).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Imatinib Low Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Imatinib 200 mg oral tablet once daily for 21 days.&#xD;
In addition to the treatment for COVID-19 Pneumonia according to the Egyptian National Protocol by the Ministry of Health (MOH).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Treatment for COVID-19 pneumonia according to the Egyptian National Protocol by the Ministry of Health (MOH).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Imatinib Mesylate</intervention_name>
    <description>Adding treatment by imatinib oral tablet into the standard treatment for moderate to severe COVID-19 pneumonia.</description>
    <arm_group_label>Imatinib Low Dose</arm_group_label>
    <arm_group_label>Imatinib Standard Dose</arm_group_label>
    <other_name>Imatinib</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard of Care</intervention_name>
    <description>Standard of Care for the Moderate to Severe COVID-19 Pneumonia as per the Egyptian National Protocol by the Ministry of Health.</description>
    <arm_group_label>Control</arm_group_label>
    <other_name>Standard</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with PCR positive for SARS-COV-2&#xD;
&#xD;
          -  Hospitalized with moderate to severe respiratory symptoms as assessed by the Egyptian&#xD;
             Ministry of Health National Guidelines&#xD;
&#xD;
          -  Informed consent explained &amp; signed by patient or his 1st degree relatives or legally&#xD;
             authorized representative.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant women (or) breast feeding women&#xD;
&#xD;
          -  Patients younger than 18 years of age&#xD;
&#xD;
          -  Patients with known allergy to imatinib&#xD;
&#xD;
          -  Total bilirubin, aspartate aminotransferase (AST), or alanine aminotransferase (ALT) &gt;&#xD;
             5x upper limit of normal (ULN).&#xD;
&#xD;
          -  Creatinine clearance (CrCl) &lt; 30 mL/minute.&#xD;
&#xD;
          -  Patient already on mechanical ventilation at time of screening.&#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>Hany ASSAAD, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alexandria</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>ASSAAD, MD, PhD</last_name>
    <phone>00201223125575</phone>
    <email>samir.assaadkhalil@alexmed.edu.eg</email>
  </overall_contact>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 5, 2020</study_first_submitted>
  <study_first_submitted_qc>June 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>June 8, 2020</last_update_submitted>
  <last_update_submitted_qc>June 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SARS-CoV-2</keyword>
  <keyword>Pneumonia</keyword>
  <keyword>ARDS</keyword>
  <keyword>Cytokine Storm</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pneumonia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Imatinib Mesylate</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/NCT04422678
org study id: Alex CCM 2020/5
nct id: NCT04422678
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
A randomized controlled pilot study on the safety & efficacy of imatinib for the treatment of
      patient with moderate to severe SARS-COV-2 induced pneumonia.
As the coronavirus disease (COVID-19) spreads worldwide, awaiting the development of a
      vaccine, researchers are looking among the arsenal of available drugs, for a potential cure
      or medication to improve patients' outcome. A highly elevated levels of cytokines in COVID-19
      patients requiring ICU admission, has suggested that a "cytokine storm" was associated with
      disease severity. Data from cellular, animal models and clinical trials, showed a beneficial
      role of tyrosine kinase inhibitors in the regulation of inflammation, the maintenance of
      endothelial barrier integrity, as well as the expression of antiviral properties. This data
      is especially derived from imatinib, the most studied Abl family kinase inhibitor, that is
      currently in clinical use for multiple medical conditions. Based on this encouraging data, we
      hypothesize that imatinib might be beneficial for the treatment of patients with SARS-CoV-2
      pneumonia, in the aim of preventing disease progression into the severe phenotype of hypoxic
      respiratory failure and acute respiratory distress syndrome.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Primary endpoint: Disease Progression
time frame: 30 Days
description: Proportion of patients with COVID-19 pneumonia progressed to critical illness in need for invasive mechanical ventilation.
measure: Improvement in Hypoxic Index
time frame: From inclusion to 30 days follow up
description: Improvement of Hypoxic index( PaO2 / FiO2) calculated daily
measure: Hospital Length of Stay
time frame: From inclusion to 30 days follow up
description: Hospital Length of stay
measure: Days on invasive mechanical ventilation
time frame: From inclusion to 30 days follow up
description: Days on mechanical ventilation for patients needing intubation & invasive mechanical ventilation
measure: Inflammatory Markers
time frame: From inclusion to 30 days
description: Difference in the median levels of serum IL-6, serum ferritin, CRP at the end of the follow up period between all groups
measure: Viral clearance
time frame: From inclusion to 30 days
description: Rate of viral clearance as monitored by SARS-COV-2 PCR
measure: Radiological assessment
time frame: From inclusion to 30 days
description: Difference in the overall evaluation of pulmonary infiltrative (improving / deteriorating) as assessed by imaging (Chest X-ray or Non-contrast pulmonary CT)
measure: Safety of Imatinib
time frame: From inclusion to 60 days
description: Rate of serious adverse events (SAEs)
arm group label: Imatinib Standard Dose
arm group type: Experimental
description: Imatinib 400 mg oral tablet once daily for 21 days
In addition for the treatment for COVID-19 pneumonia according to the Egyptian National Protocol by the Ministry of Health (MOH).
arm group label: Imatinib Low Dose
arm group type: Experimental
description: Imatinib 200 mg oral tablet once daily for 21 days.
In addition to the treatment for COVID-19 Pneumonia according to the Egyptian National Protocol by the Ministry of Health (MOH).
arm group label: Control
arm group type: Active Comparator
description: Treatment for COVID-19 pneumonia according to the Egyptian National Protocol by the Ministry of Health (MOH).
intervention type: Drug
intervention name: Imatinib Mesylate
description: Adding treatment by imatinib oral tablet into the standard treatment for moderate to severe COVID-19 pneumonia.
arm group label: Imatinib Low Dose
arm group label: Imatinib Standard Dose
other name: Imatinib
intervention type: Drug
intervention name: Standard of Care
description: Standard of Care for the Moderate to Severe COVID-19 Pneumonia as per the Egyptian National Protocol by the Ministry of Health.
arm group label: Control
other name: Standard
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hany ASSAAD, MD, PhD
role: Principal Investigator
affiliation: University of Alexandria
last name: ASSAAD, MD, PhD
phone: 00201223125575
email: samir.assaadkhalil@alexmed.edu.eg
responsible party type: Sponsor
mesh term: Pneumonia
mesh term: Imatinib Mesylate
sharing ipd: No