<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/NCT04415086</url>
  </required_header>
  <id_info>
    <org_study_id>COOP-COVID-19-MCTIC</org_study_id>
    <nct_id>NCT04415086</nct_id>
  </id_info>
  <brief_title>Treatment of Patients With COVID-19 With Convalescent Plasma</brief_title>
  <acronym>COOPCOVID-19</acronym>
  <official_title>Treatment of Patients With COVID-19 With Convalescent Plasma Transfusion: a Multicenter, Open-labeled, Randomized and Controlled Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministério da Ciência, Tecnologia, Inovações e Comunicações</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Faculty of Medicine of Ribeirão Preto (FMRP-USP)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital de Clínicas, Faculdade de Medicina Universidade Estadual de Campinas</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Sirio-Libanes</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Israelita Albert Einstein</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Grupo Hospitalar Conceição</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospital Ernesto Dornelles</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Sao Paulo General Hospital</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>
      The COVID-19 pandemic has been spreading continuously, and in Brazil, until May 31, 2020,&#xD;
      there have been more than 450.000 cases with more than 28.000 deaths, with daily increases.&#xD;
      The present study proposes to evaluate the efficacy and safety of convalescent plasma in&#xD;
      treatment of severe cases of COVID-19 in a multicenter, randomized, open-label and controlled&#xD;
      study&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Eligible patients will be randomized 1:1:1 into 3 treatment groups: A- standard (control); B-&#xD;
      standard and convalescent plasma in a volume of 200ml (150-300ml); C- standard and&#xD;
      convalescent plasma in a volume of 400ml (300-600ml). The Bayesian multi-arm and multi-stage&#xD;
      model will be used, which will allow an interim analysis after the inclusion of 30 patients,&#xD;
      with repeated interim analyses for every 30 additional patients. With this, we expect to&#xD;
      define not only the efficacy of convalescent plasma, but also the volume of plasma needed if&#xD;
      efficacy is proven. The study will be interrupted if the efficacy of the convalescent plasma&#xD;
      group is proven, so that all severely ill patients as defined in the study can receive the&#xD;
      convalescent plasma treatment. The same will occur if there is no difference in primary&#xD;
      outcome with the use of convalescent plasma or serious adverse effects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2020</start_date>
  <completion_date type="Actual">February 15, 2022</completion_date>
  <primary_completion_date type="Actual">February 15, 2022</primary_completion_date>
  <phase>Phase 2</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>1:1:1 into 3 treatment groups: A- standard (control); B- standard and convalescent plasma in a volume of 200ml (150-300ml); C- standard and convalescent plasma in a volume of 400ml (300-600ml)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time elapsed until clinical improvement or hospital discharge</measure>
    <time_frame>Follow up until 28 days after transfusion</time_frame>
    <description>clinical improvement is defined as the time from the randomization date until the decline of 2 categories on the ordinal scale of 10 categories or hospital discharge (whichever comes first)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>acute adverse events</measure>
    <time_frame>Up to 12 hours after transfusion</time_frame>
    <description>incidence of acute adverse events possibly or definitively realted to convalescent plasma transfusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Status</measure>
    <time_frame>&quot;Day 7&quot;, &quot;Day 14&quot; and &quot;Day 28&quot;</time_frame>
    <description>Evaluation according to an ordinal scale of 10 categories</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of clinical events</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>Duration of mechanical ventilation, length of hospital stay in survivors up to 28 days and time from the beginning of treatment to death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SARS-CoV-2 in nasopharyngeal swab</measure>
    <time_frame>Days 0, 1, 3, 7, 14 and 28 after transfusion and control groups</time_frame>
    <description>Detection of SARS-CoV-2 in nasopharyngeal swab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>IgG, IgM and IgA titers for SARS-CoV-2</measure>
    <time_frame>Days 0, 1, 3, 5, 7, 14 and 28 after transfusion and control groups</time_frame>
    <description>Specific IgG, IgM and IgA titers for SARS-CoV-2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neutralizing antibodies</measure>
    <time_frame>0,1,7 14 and 28 days after transfusion and control groups</time_frame>
    <description>Titers of neutralizing antibodies</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">129</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Participants will receive the standard of care treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive the standard treatment and convalescent plasma in a volume of 200ml (150-300ml)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group C</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive the standard treatment and convalescent plasma in a volume of 400ml (300-600ml)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>convalescent plasma</intervention_name>
    <description>The study will be interrupted if the efficacy of the convalescent plasma group is proven, so that all severely ill patients as defined in the study can receive the convalescent plasma treatment. The same will occur if there is no difference in primary outcome with the use of convalescent plasma or serious adverse effects.</description>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_label>Group C</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age = or &gt; than 18 years; .&#xD;
&#xD;
          -  Laboratory-proven COVID-19 infection by RT-PCR in any clinical sample . Time since&#xD;
             symptom onset less than 10 days at the time of screening; - . Presence of COVID-19&#xD;
             pneumonia, with a typical, indeterminate or atypical compatible image in a chest&#xD;
             tomography exam (see definition below) -&#xD;
&#xD;
          -  Presence of one of the following criteria:&#xD;
&#xD;
          -  Need for&gt; 3L of O2 in the catheter / mask or&gt; 25% in the Venturi mask to maintain O2&#xD;
             saturation&gt; 92% B presence of respiratory distress syndrome with PaO2 / FiO2 &lt;300mmHg&#xD;
             If intubated, within 48 hours of orotracheal intubation&#xD;
&#xD;
          -  Absence of a history of serious adverse reactions to transfusion, for example,&#xD;
             anaphylaxis; - .Participation approval by the research clinician&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Already enrolled in another clinical trial evaluating antiviral or immunobiological&#xD;
             therapy for the treatment of COVID-19.&#xD;
&#xD;
          -  IgA deficiency&#xD;
&#xD;
          -  Presence of a clinical condition that does not allow infusion of 400 ml of volume at&#xD;
             clinical discretion&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Receipt of immunoglobulin in the last 30 days&#xD;
&#xD;
          -  Presence of significant risk of death within the next 48 hours at clinical discretion.&#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>Esper G Kallás, PhD, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Sao Paulo General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Sao Paulo - General Hospital</name>
      <address>
        <city>São Paulo</city>
        <state>SP</state>
        <zip>01403-002</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>May 17, 2022</last_update_submitted>
  <last_update_submitted_qc>May 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>convalescent plasma</keyword>
  <keyword>efficacy</keyword>
  <keyword>safety</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 2, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT04415086/SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT04415086
org study id: COOP-COVID-19-MCTIC
nct id: NCT04415086
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The COVID-19 pandemic has been spreading continuously, and in Brazil, until May 31, 2020,
      there have been more than 450.000 cases with more than 28.000 deaths, with daily increases.
      The present study proposes to evaluate the efficacy and safety of convalescent plasma in
      treatment of severe cases of COVID-19 in a multicenter, randomized, open-label and controlled
      study
Eligible patients will be randomized 1:1:1 into 3 treatment groups: A- standard (control); B-
      standard and convalescent plasma in a volume of 200ml (150-300ml); C- standard and
      convalescent plasma in a volume of 400ml (300-600ml). The Bayesian multi-arm and multi-stage
      model will be used, which will allow an interim analysis after the inclusion of 30 patients,
      with repeated interim analyses for every 30 additional patients. With this, we expect to
      define not only the efficacy of convalescent plasma, but also the volume of plasma needed if
      efficacy is proven. The study will be interrupted if the efficacy of the convalescent plasma
      group is proven, so that all severely ill patients as defined in the study can receive the
      convalescent plasma treatment. The same will occur if there is no difference in primary
      outcome with the use of convalescent plasma or serious adverse effects.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 1:1:1 into 3 treatment groups: A- standard (control); B- standard and convalescent plasma in a volume of 200ml (150-300ml); C- standard and convalescent plasma in a volume of 400ml (300-600ml)
primary purpose: Treatment
masking: None (Open Label)
measure: Time elapsed until clinical improvement or hospital discharge
time frame: Follow up until 28 days after transfusion
description: clinical improvement is defined as the time from the randomization date until the decline of 2 categories on the ordinal scale of 10 categories or hospital discharge (whichever comes first)
measure: acute adverse events
time frame: Up to 12 hours after transfusion
description: incidence of acute adverse events possibly or definitively realted to convalescent plasma transfusion
measure: Clinical Status
time frame: "Day 7", "Day 14" and "Day 28"
description: Evaluation according to an ordinal scale of 10 categories
measure: Duration of clinical events
time frame: Up to 28 days
description: Duration of mechanical ventilation, length of hospital stay in survivors up to 28 days and time from the beginning of treatment to death
measure: SARS-CoV-2 in nasopharyngeal swab
time frame: Days 0, 1, 3, 7, 14 and 28 after transfusion and control groups
description: Detection of SARS-CoV-2 in nasopharyngeal swab
measure: IgG, IgM and IgA titers for SARS-CoV-2
time frame: Days 0, 1, 3, 5, 7, 14 and 28 after transfusion and control groups
description: Specific IgG, IgM and IgA titers for SARS-CoV-2
measure: Neutralizing antibodies
time frame: 0,1,7 14 and 28 days after transfusion and control groups
description: Titers of neutralizing antibodies
arm group label: Group A
arm group type: Sham Comparator
description: Participants will receive the standard of care treatment
arm group label: Group B
arm group type: Active Comparator
description: Participants will receive the standard treatment and convalescent plasma in a volume of 200ml (150-300ml)
arm group label: Group C
arm group type: Active Comparator
description: Participants will receive the standard treatment and convalescent plasma in a volume of 400ml (300-600ml)
intervention type: Biological
intervention name: convalescent plasma
description: The study will be interrupted if the efficacy of the convalescent plasma group is proven, so that all severely ill patients as defined in the study can receive the convalescent plasma treatment. The same will occur if there is no difference in primary outcome with the use of convalescent plasma or serious adverse effects.
arm group label: Group A
arm group label: Group B
arm group label: Group C
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Esper G Kallás, PhD, MD
role: Principal Investigator
affiliation: University of Sao Paulo General Hospital
facility: 
country: Brazil
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: No
provided document: 