<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/NCT04408209</url>
  </required_header>
  <id_info>
    <org_study_id>245-14-4-20</org_study_id>
    <nct_id>NCT04408209</nct_id>
  </id_info>
  <brief_title>Convalescent Plasma for the Treatment of Patients With Severe COVID-19 Infection</brief_title>
  <official_title>Convalescent Plasma for the Treatment of Patients With Severe COVID-19 Infection - A Multicenter Phase II Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National and Kapodistrian University of Athens</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hellenic Society of Hematology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>National and Kapodistrian University of Athens</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter, Phase 2 study, to assess the efficacy of the treatment with&#xD;
      convalescent plasma in patients with severe COVID-19 infection.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Convalescent plasma will be collected by plasmapheresis from patients fully recovered from&#xD;
      COVID-19 infection and will be administered in patients with severe COVID-19 infection. The&#xD;
      results will be compared with an historical matched control.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 23, 2020</start_date>
  <completion_date type="Anticipated">December 15, 2023</completion_date>
  <primary_completion_date type="Anticipated">August 30, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Single arm</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Survival</measure>
    <time_frame>Day 21</time_frame>
    <description>The primary endpoint of this trial is the survival on day 21. The primary endpoint, as a dichotomous composite of survival (yes/no) and no longer fulfilling criteria of severe COVID-19, will be analyzed according their classification. Specifically, categorical variables will be analyzed by means of absolute and relative frequencies, and all continuous variables will be described using arithmetic mean, standard deviation, median, quartiles. Also, geometric means, variance and 95% confidence intervals (CI), will be calculated for all pharmacokinetics parameters.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Survival</measure>
    <time_frame>Day 35</time_frame>
    <description>The primary endpoint of this trial is the survival on day 35.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Survival</measure>
    <time_frame>Day 60</time_frame>
    <description>The primary endpoint of this trial is the survival on day 60.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical improvement ie percentage of patients not fulfilling the criteria for severe disease</measure>
    <time_frame>Day 21</time_frame>
    <description>The secondary endpoint of this trial is that no longer fulfilling criteria of severe COVID-19 within 21 days after inclusion. This will be assessed on the basis of respiratory rate and ventilation support.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>COVID-19 Infection</condition>
  <arm_group>
    <arm_group_label>Convalescent Plasma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Convalescent Plasma - early treatment of patients with severe COVID-19</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Convalescent Plasma</intervention_name>
    <description>Convalescent Plasma - early treatment of patients with severe COVID-19. Clinical and laboratory data of patients will be collected before initiation of the procedure, 30 minutes after the first dose, 30 minutes after the second dose and 30 minutes after the third plasma dose and then on days 1-7, 14, 21, 28, 35 from the start of treatment. In case of adverse reactions during transfusion such as acute shortness of breath, haemodynamic instability or high pre-existing and non-disease-related fever, the transfusion will be interrupted and detailed recording of the event as well as updating the Adverse Events Management Committee will be performed.&#xD;
In addition to the standard assessments, the titer of neutralizing anti-SARS-CoV-2 antibodies will be measured in a sample drawn prior to plasmapheresis.&#xD;
All donors will be tested for:&#xD;
the titer of IgG anti-SARS-CoV-2 antibodies (Pasteur Institute)&#xD;
the titer of neutralizing anti-SARS-CoV-2 antibodies (Pasteur Institute)</description>
    <arm_group_label>Convalescent Plasma</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age &gt;18 years&#xD;
&#xD;
          2. Confirmed SARS-CoV2 infection by PCR of the nasal/pharyngeal swab, sputum, BAL&#xD;
&#xD;
          3. Onset of the disease symptoms no more than 12 days before the inclusion of the&#xD;
             patients in the trial&#xD;
&#xD;
          4. Severe COVID-19 infection as determined with one of the following:&#xD;
&#xD;
               -  Respiratory rate 30/min&#xD;
&#xD;
               -  Oxygen Hemoglobin Saturation SAT 93&#xD;
&#xD;
               -  CRP &gt;1.5 (upper normal limit &lt;0.5)&#xD;
&#xD;
               -  Ferritin value &gt;100&#xD;
&#xD;
               -  Ratio of PaO2:FiO2 &lt;300mmHg&#xD;
&#xD;
               -  Pulmonary infiltrates in Chest X-Ray or Chest CT scan &gt;50% during 24-48 hours&#xD;
&#xD;
          5. Life threatening infection as determined by one of the following:&#xD;
&#xD;
               -  Respiratory failure&#xD;
&#xD;
               -  Septic Shock&#xD;
&#xD;
               -  Multiple organ failure&#xD;
&#xD;
          6. Signature of informed consent by the patient or legal representative Patients&#xD;
             fulfilling criteria 1, 2, 3, 6 and one of criteria 4 or 5 will be eligible for the&#xD;
             study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Critical illness due to progressive COVID-19 with expected survival time &lt;48 hours&#xD;
&#xD;
          2. Intubated patients &gt;72 hours&#xD;
&#xD;
          3. Chronic Heart failure NYHA 3 and/or preexisting left ventricular ejection fraction 30%&#xD;
&#xD;
          4. Cardiovascular failure requiring 0.5μg/Kg/min nor-adrenaline or equivalent or more&#xD;
             than 2 types of vasopressor medication&#xD;
&#xD;
          5. Liver Cirrhosis Child C&#xD;
&#xD;
          6. Liver failure with bilirubin &gt;5X ULN and increase of ALT/AST (at least one &gt;10X ULN)&#xD;
&#xD;
          7. Previous history of allergic reaction to blood or blood products transfusion&#xD;
&#xD;
          8. Known IgA deficiency&#xD;
&#xD;
          9. Pregnancy&#xD;
&#xD;
         10. Breast feeding women&#xD;
&#xD;
         11. Pulmonary edema&#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>Meletios Athanasios Dimopoulos</last_name>
    <role>Principal Investigator</role>
    <affiliation>National and Kapodistrian University of Athens</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Evangelos Terpos, MD</last_name>
    <role>Study Chair</role>
    <affiliation>National and Kapodistrian University of Athens</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Aikaterini Niarchou</last_name>
    <phone>+30 6949124743</phone>
    <email>aniarchou@med.uoa.gr</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Ioanna Charitaki</last_name>
    <phone>+30 6976156403</phone>
    <email>j.charitaki@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>&quot;Evangelismos&quot; General Hospital</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>10676</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>&quot;Agios Savas&quot; Oncology Hospital</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>115 22</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>&quot;Alexandra&quot; General Hospital</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>115 28</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>&quot;Sotiria&quot; General Hospital</name>
      <address>
        <city>Athens</city>
        <state>Attiki</state>
        <zip>11527</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Attikon&quot; University General Hospital</name>
      <address>
        <city>Athens</city>
        <state>Chaidari</state>
        <zip>124 62</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University General Hospital of Patras</name>
      <address>
        <city>Patra</city>
        <state>Rio</state>
        <zip>26504</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>May 25, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>September 26, 2022</last_update_submitted>
  <last_update_submitted_qc>September 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National and Kapodistrian University of Athens</investigator_affiliation>
    <investigator_full_name>Professor Meletios-Athanasios Dimopoulos</investigator_full_name>
    <investigator_title>Professor &amp; Rector of the NKU Athens Plasma Cell Dyscrasias Unit Section of Hematology &amp; Medical Oncology Department of Clinical Therapeutics School of Medicine NKU Athens Alexandra Hospital</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04408209
org study id: 245-14-4-20
nct id: NCT04408209
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a multicenter, Phase 2 study, to assess the efficacy of the treatment with
      convalescent plasma in patients with severe COVID-19 infection.
Convalescent plasma will be collected by plasmapheresis from patients fully recovered from
      COVID-19 infection and will be administered in patients with severe COVID-19 infection. The
      results will be compared with an historical matched control.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Single arm
primary purpose: Treatment
masking: None (Open Label)
measure: Survival
time frame: Day 21
description: The primary endpoint of this trial is the survival on day 21. The primary endpoint, as a dichotomous composite of survival (yes/no) and no longer fulfilling criteria of severe COVID-19, will be analyzed according their classification. Specifically, categorical variables will be analyzed by means of absolute and relative frequencies, and all continuous variables will be described using arithmetic mean, standard deviation, median, quartiles. Also, geometric means, variance and 95% confidence intervals (CI), will be calculated for all pharmacokinetics parameters.
measure: Survival
time frame: Day 35
description: The primary endpoint of this trial is the survival on day 35.
measure: Survival
time frame: Day 60
description: The primary endpoint of this trial is the survival on day 60.
measure: Clinical improvement ie percentage of patients not fulfilling the criteria for severe disease
time frame: Day 21
description: The secondary endpoint of this trial is that no longer fulfilling criteria of severe COVID-19 within 21 days after inclusion. This will be assessed on the basis of respiratory rate and ventilation support.
arm group label: Convalescent Plasma
arm group type: Experimental
description: Convalescent Plasma - early treatment of patients with severe COVID-19
intervention type: Procedure
intervention name: Convalescent Plasma
description: Convalescent Plasma - early treatment of patients with severe COVID-19. Clinical and laboratory data of patients will be collected before initiation of the procedure, 30 minutes after the first dose, 30 minutes after the second dose and 30 minutes after the third plasma dose and then on days 1-7, 14, 21, 28, 35 from the start of treatment. In case of adverse reactions during transfusion such as acute shortness of breath, haemodynamic instability or high pre-existing and non-disease-related fever, the transfusion will be interrupted and detailed recording of the event as well as updating the Adverse Events Management Committee will be performed.
In addition to the standard assessments, the titer of neutralizing anti-SARS-CoV-2 antibodies will be measured in a sample drawn prior to plasmapheresis.
All donors will be tested for:
the titer of IgG anti-SARS-CoV-2 antibodies (Pasteur Institute)
the titer of neutralizing anti-SARS-CoV-2 antibodies (Pasteur Institute)
arm group label: Convalescent Plasma
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Meletios Athanasios Dimopoulos
role: Principal Investigator
affiliation: National and Kapodistrian University of Athens
last name: Evangelos Terpos, MD
role: Study Chair
affiliation: National and Kapodistrian University of Athens
last name: Aikaterini Niarchou
phone: +30 6949124743
email: aniarchou@med.uoa.gr
last name: Ioanna Charitaki
phone: +30 6976156403
email: j.charitaki@gmail.com
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
country: Greece
responsible party type: Principal Investigator
investigator affiliation: National and Kapodistrian University of Athens
investigator full name: Professor Meletios-Athanasios Dimopoulos
investigator title: Professor & Rector of the NKU Athens Plasma Cell Dyscrasias Unit Section of Hematology & Medical Oncology Department of Clinical Therapeutics School of Medicine NKU Athens Alexandra Hospital
mesh term: Infections
mesh term: Communicable Diseases
mesh term: COVID-19
sharing ipd: No