<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/NCT04421404</url>
  </required_header>
  <id_info>
    <org_study_id>20-30794</org_study_id>
    <nct_id>NCT04421404</nct_id>
  </id_info>
  <brief_title>Effects of COVID-19 Convalescent Plasma (CCP) on Coronavirus-associated Complications in Hospitalized Patients</brief_title>
  <acronym>CAPRI</acronym>
  <official_title>A Randomized Controlled Adaptive Study Comparing COVID-19 Convalescent Plasma (CCP) to Non-immune Plasma to Limit Coronavirus-associated Complications in Hospitalized Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Priscilla Hsue, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Vitalant Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>San Francisco General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study assess the efficacy and safety of anti-SARS-CoV-2 convalescent&#xD;
      plasma in hospitalized patients with acute respiratory symptoms up to 14 days after the onset&#xD;
      of initial symptoms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A total of 50 eligible subjects will be randomized in a 1:1 ratio to receive either&#xD;
      convalescent fresh frozen plasma (frozen within 8 hours of collection) of PF24 (frozen within&#xD;
      24 hours) from blood donors who have recovered from COVID-19 containing antibodies to&#xD;
      SARS-CoV-2 or control (standard fresh frozen plasma collected prior to 12/1/2019 or with&#xD;
      documented negative SARS-CoV-2 antibody). Should additional anti-COVID agents (anti-viral&#xD;
      and/or anti-inflammatory) become available for use as standard of care during implementation,&#xD;
      the sample size will be recalculated and increased to account for the estimated impact that&#xD;
      these agents may have on the reducing the progression to the primary endpoint of severe&#xD;
      hypoxemia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 9, 2020</start_date>
  <completion_date type="Actual">April 30, 2021</completion_date>
  <primary_completion_date type="Actual">April 30, 2021</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>Subjects enrolled in the study will be randomized using a web based randomization procedure to receive convalescent plasma versus non-immune plasma at a 1:1 ratio.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Study investigators analyzing the data and participants will be blinded to the randomization. It may not be feasible to blind nursing staff to the treatment assignment to ensure proper ABO checking of the plasma unit at bedside per standard transfusion procedures, but every effort will be made to preserve blinding of the investigators, participant, and primary team providing care. An unblinded research assistant who is not involved in other aspects of the study will randomize the participant once enrolled. Randomization will be provided to an unblinded provider who is not part of the care team who will place the order for the plasma (CCP vs. control plasma) using a paper order that will not be part of the electronic medical record. The safety monitoring committee (SMC) will review study data, including unblinded data, to evaluate the safety, efficacy, study progress, and conduct of the study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Mechanical Ventilation or Death Endpoint</measure>
    <time_frame>Day 14</time_frame>
    <description>Number of participants that progressed to mechanical ventilation or death within the first 14 days of enrollment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mechanical Ventilation or Death Endpoint</measure>
    <time_frame>Day 28</time_frame>
    <description>Progression to mechanical ventilation or death within the first 28 days of enrollment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>8-Point Ordinal Scale Endpoint</measure>
    <time_frame>Day 29</time_frame>
    <description>Clinical efficacy of CCP relative to the control arm in adults hospitalized with COVID-19 according to clinical status as assessed by 8-point ordinal scale.&#xD;
8 Point WHO Ordinal Scale of Clinical Status:&#xD;
Uninfected (No clinical or virological evidence of infection) - 0&#xD;
Ambulatory (No limitation of activities) - 1 Ambulatory (Limitation of Activities) - 2&#xD;
Hospitalized Mild Disease (Hospitalized, no oxygen therapy) - 3 Hospitalized Mild Disease (Oxygen by mask or nasal prongs) - 4&#xD;
Hospitalized Severe Disease (Non-invasive ventilation or high flow oxygen) - 5 Hospitalized Severe Disease (Intubation and mechanical ventilation) - 6 Hospitalized Severe Disease (Ventilation + Additional organ support (pressors, RRT, ECMO)) - 7&#xD;
Dead (Death) - 8</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>COVID-19</condition>
  <condition>Sars-CoV2</condition>
  <arm_group>
    <arm_group_label>COVID-19 Convalescent Plasma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in the COVID-19 convalescent plasma group will receive a single infusion of 250 ml anti-SARS-CoV-2 convalescent fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects in the placebo group will receive a single infusion of 250 ml of standard fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>COVID-19 Convalescent Plasma (CCP)</intervention_name>
    <description>COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.</description>
    <arm_group_label>COVID-19 Convalescent Plasma</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria for Enrollment:&#xD;
&#xD;
          1. Patients ≥18 years of age&#xD;
&#xD;
          2. Hospitalized with COVID-19&#xD;
&#xD;
          3. Enrolled within 72 hours of hospitalization OR within day 14 from first signs of&#xD;
             illness&#xD;
&#xD;
          4. Pulmonary infiltrates on chest imaging&#xD;
&#xD;
          5. Oxygenation of &lt;95% on room air&#xD;
&#xD;
          6. Laboratory confirmed COVID-19&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Contraindication to transfusion due to inability to tolerate additional fluid, such as&#xD;
             due to decompensated congestive heart failure&#xD;
&#xD;
          2. Baseline requirement for oxygen supplementation prior to COVID-19 infection or use of&#xD;
             positive pressure therapy for sleep disordered breathing&#xD;
&#xD;
          3. Currently experiencing severe hypoxemic failure, as defined in study endpoints&#xD;
&#xD;
          4. Prior receipt of plasma products, IVIG, or hyperimmune globulin within past 3 months&#xD;
&#xD;
          5. Not currently enrolled another interventional clinical trial of COVID-19 treatment.&#xD;
&#xD;
        Note: If taking medications with potential anti-COVID activity for the purpose of COVID-19&#xD;
        treatment that do not yet have data to support efficacy, such as IL-6 antagonists, these&#xD;
        medications must be stopped prior to enrollment. Receipt of current standard of care&#xD;
        COVID-19 treatment, including remdesivir and dexamethasone is permitted and should be&#xD;
        recorded as a concomitant medication.&#xD;
&#xD;
        Note: Pregnancy is not exclusionary but will merit additional discussion of risks &amp;&#xD;
        benefits in the context of ongoing pregnancy&#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>Priscilla Hsue, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Annie Leutkemeyer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>San Francisco General Hospital</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSF Medical Center at Mount Zion</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco Medical Center (Parnassus Campus)</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <results_first_submitted>May 18, 2021</results_first_submitted>
  <results_first_submitted_qc>August 23, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 25, 2021</results_first_posted>
  <last_update_submitted>October 5, 2022</last_update_submitted>
  <last_update_submitted_qc>October 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 7, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Francisco</investigator_affiliation>
    <investigator_full_name>Priscilla Hsue, MD</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>Sars-CoV2</keyword>
  <keyword>Convalescent plasma</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>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 26, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT04421404/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 29, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT04421404/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>COVID-19 Convalescent Plasma</title>
          <description>Subjects in the COVID-19 convalescent plasma group will receive a single infusion of 250 ml anti-SARS-CoV-2 convalescent fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.&#xD;
COVID-19 Convalescent Plasma (CCP): COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Subjects in the placebo group will receive a single infusion of 250 ml of standard fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.&#xD;
Placebo: Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>COVID-19 Convalescent Plasma</title>
          <description>Subjects in the COVID-19 convalescent plasma group will receive a single infusion of 250 ml anti-SARS-CoV-2 convalescent fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.&#xD;
COVID-19 Convalescent Plasma (CCP): COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Subjects in the placebo group will receive a single infusion of 250 ml of standard fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.&#xD;
Placebo: Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
            <count group_id="B2" value="18"/>
            <count group_id="B3" value="34"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="52" lower_limit="40" upper_limit="64"/>
                    <measurement group_id="B2" value="62" lower_limit="49" upper_limit="74"/>
                    <measurement group_id="B3" value="57" lower_limit="44" upper_limit="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mechanical Ventilation or Death Endpoint</title>
        <description>Number of participants that progressed to mechanical ventilation or death within the first 14 days of enrollment.</description>
        <time_frame>Day 14</time_frame>
        <group_list>
          <group group_id="O1">
            <title>COVID-19 Convalescent Plasma</title>
            <description>Subjects in the COVID-19 convalescent plasma group will receive a single infusion of 250 ml anti-SARS-CoV-2 convalescent fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.&#xD;
COVID-19 Convalescent Plasma (CCP): COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Subjects in the placebo group will receive a single infusion of 250 ml of standard fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.&#xD;
Placebo: Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.</description>
          </group>
        </group_list>
        <measure>
          <title>Mechanical Ventilation or Death Endpoint</title>
          <description>Number of participants that progressed to mechanical ventilation or death within the first 14 days of enrollment.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mechanical Ventilation or Death Endpoint</title>
        <description>Progression to mechanical ventilation or death within the first 28 days of enrollment.</description>
        <time_frame>Day 28</time_frame>
        <group_list>
          <group group_id="O1">
            <title>COVID-19 Convalescent Plasma</title>
            <description>Subjects in the COVID-19 convalescent plasma group will receive a single infusion of 250 ml anti-SARS-CoV-2 convalescent fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.&#xD;
COVID-19 Convalescent Plasma (CCP): COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Subjects in the placebo group will receive a single infusion of 250 ml of standard fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.&#xD;
Placebo: Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.</description>
          </group>
        </group_list>
        <measure>
          <title>Mechanical Ventilation or Death Endpoint</title>
          <description>Progression to mechanical ventilation or death within the first 28 days of enrollment.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>8-Point Ordinal Scale Endpoint</title>
        <description>Clinical efficacy of CCP relative to the control arm in adults hospitalized with COVID-19 according to clinical status as assessed by 8-point ordinal scale.&#xD;
8 Point WHO Ordinal Scale of Clinical Status:&#xD;
Uninfected (No clinical or virological evidence of infection) - 0&#xD;
Ambulatory (No limitation of activities) - 1 Ambulatory (Limitation of Activities) - 2&#xD;
Hospitalized Mild Disease (Hospitalized, no oxygen therapy) - 3 Hospitalized Mild Disease (Oxygen by mask or nasal prongs) - 4&#xD;
Hospitalized Severe Disease (Non-invasive ventilation or high flow oxygen) - 5 Hospitalized Severe Disease (Intubation and mechanical ventilation) - 6 Hospitalized Severe Disease (Ventilation + Additional organ support (pressors, RRT, ECMO)) - 7&#xD;
Dead (Death) - 8</description>
        <time_frame>Day 29</time_frame>
        <population>The number of participants in the table below differs, as these are the number of participants per visit day. The number of participants decreased over the visit days as there was loss to follow up.</population>
        <group_list>
          <group group_id="O1">
            <title>COVID-19 Convalescent Plasma</title>
            <description>Subjects in the COVID-19 convalescent plasma group will receive a single infusion of 250 ml anti-SARS-CoV-2 convalescent fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.&#xD;
COVID-19 Convalescent Plasma (CCP): COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Subjects in the placebo group will receive a single infusion of 250 ml of standard fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.&#xD;
Placebo: Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.</description>
          </group>
        </group_list>
        <measure>
          <title>8-Point Ordinal Scale Endpoint</title>
          <description>Clinical efficacy of CCP relative to the control arm in adults hospitalized with COVID-19 according to clinical status as assessed by 8-point ordinal scale.&#xD;
8 Point WHO Ordinal Scale of Clinical Status:&#xD;
Uninfected (No clinical or virological evidence of infection) - 0&#xD;
Ambulatory (No limitation of activities) - 1 Ambulatory (Limitation of Activities) - 2&#xD;
Hospitalized Mild Disease (Hospitalized, no oxygen therapy) - 3 Hospitalized Mild Disease (Oxygen by mask or nasal prongs) - 4&#xD;
Hospitalized Severe Disease (Non-invasive ventilation or high flow oxygen) - 5 Hospitalized Severe Disease (Intubation and mechanical ventilation) - 6 Hospitalized Severe Disease (Ventilation + Additional organ support (pressors, RRT, ECMO)) - 7&#xD;
Dead (Death) - 8</description>
          <population>The number of participants in the table below differs, as these are the number of participants per visit day. The number of participants decreased over the visit days as there was loss to follow up.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="14"/>
                    <count group_id="O2" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.43" lower_limit="1" upper_limit="4"/>
                    <measurement group_id="O2" value="1.93" lower_limit="1" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                    <count group_id="O2" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.15" lower_limit="1" upper_limit="4"/>
                    <measurement group_id="O2" value="2.14" lower_limit="1" upper_limit="3.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.92" lower_limit="3" upper_limit="4"/>
                    <measurement group_id="O2" value="4" lower_limit="4" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.42" lower_limit="3" upper_limit="4"/>
                    <measurement group_id="O2" value="3.69" lower_limit="3.5" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 5</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.83" lower_limit="1" upper_limit="4"/>
                    <measurement group_id="O2" value="2.92" lower_limit="2.5" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.18" lower_limit="0.5" upper_limit="3.5"/>
                    <measurement group_id="O2" value="2.45" lower_limit="0" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.4" lower_limit="1" upper_limit="5"/>
                    <measurement group_id="O2" value="3.5" lower_limit="3" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="4.5" upper_limit="5.5"/>
                    <measurement group_id="O2" value="2.57" lower_limit="2" upper_limit="3.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 9</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.67" lower_limit="4" upper_limit="5.5"/>
                    <measurement group_id="O2" value="1.86" lower_limit="0.5" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 10</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.67" lower_limit="2.5" upper_limit="5.5"/>
                    <measurement group_id="O2" value="1.8" lower_limit="0" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="4.5" upper_limit="5.5"/>
                    <measurement group_id="O2" value="2.5" lower_limit="2.25" upper_limit="2.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="4.5" upper_limit="5.5"/>
                    <measurement group_id="O2" value="2" lower_limit="1.5" upper_limit="2.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 13</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" lower_limit="1.5" upper_limit="4.5"/>
                    <measurement group_id="O2" value="2.5" lower_limit="2.25" upper_limit="2.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2" lower_limit="0" upper_limit="3"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6" lower_limit="6" upper_limit="6"/>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6" lower_limit="6" upper_limit="6"/>
                    <measurement group_id="O2" value="8" lower_limit="8" upper_limit="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 17</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6" lower_limit="6" upper_limit="6"/>
                    <measurement group_id="O2" value="8" lower_limit="8" upper_limit="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6" lower_limit="6" upper_limit="6"/>
                    <measurement group_id="O2" value="8" lower_limit="8" upper_limit="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 19</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6" lower_limit="6" upper_limit="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6" lower_limit="6" upper_limit="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8" lower_limit="8" upper_limit="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 22</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8" lower_limit="8" upper_limit="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 29</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="0" lower_limit="0" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>90 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>COVID-19 Convalescent Plasma</title>
          <description>Subjects in the COVID-19 convalescent plasma group will receive a single infusion of 250 ml anti-SARS-CoV-2 convalescent fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.&#xD;
COVID-19 Convalescent Plasma (CCP): COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Subjects in the placebo group will receive a single infusion of 250 ml of standard fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.&#xD;
Placebo: Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Intubation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension (transfusion reaction)</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated triglycerides</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated LFTs</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>UTI</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>This study was limited by the small sample of hospitalized, hypoxic patients, limiting the generalizability of the results. Most participants were beyond 72 hours of symptom onset, the period when studies suggest CCP is most likely to be beneficial.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Annie Luetkemeyer</name_or_title>
      <organization>UCSF</organization>
      <phone>415-476-4082 ext 130</phone>
      <email>annie.luetkemeyer@ucsf.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04421404
org study id: 20-30794
nct id: NCT04421404
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study assess the efficacy and safety of anti-SARS-CoV-2 convalescent
      plasma in hospitalized patients with acute respiratory symptoms up to 14 days after the onset
      of initial symptoms.
A total of 50 eligible subjects will be randomized in a 1:1 ratio to receive either
      convalescent fresh frozen plasma (frozen within 8 hours of collection) of PF24 (frozen within
      24 hours) from blood donors who have recovered from COVID-19 containing antibodies to
      SARS-CoV-2 or control (standard fresh frozen plasma collected prior to 12/1/2019 or with
      documented negative SARS-CoV-2 antibody). Should additional anti-COVID agents (anti-viral
      and/or anti-inflammatory) become available for use as standard of care during implementation,
      the sample size will be recalculated and increased to account for the estimated impact that
      these agents may have on the reducing the progression to the primary endpoint of severe
      hypoxemia.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Subjects enrolled in the study will be randomized using a web based randomization procedure to receive convalescent plasma versus non-immune plasma at a 1:1 ratio.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Study investigators analyzing the data and participants will be blinded to the randomization. It may not be feasible to blind nursing staff to the treatment assignment to ensure proper ABO checking of the plasma unit at bedside per standard transfusion procedures, but every effort will be made to preserve blinding of the investigators, participant, and primary team providing care. An unblinded research assistant who is not involved in other aspects of the study will randomize the participant once enrolled. Randomization will be provided to an unblinded provider who is not part of the care team who will place the order for the plasma (CCP vs. control plasma) using a paper order that will not be part of the electronic medical record. The safety monitoring committee (SMC) will review study data, including unblinded data, to evaluate the safety, efficacy, study progress, and conduct of the study.
measure: Mechanical Ventilation or Death Endpoint
time frame: Day 14
description: Number of participants that progressed to mechanical ventilation or death within the first 14 days of enrollment.
measure: Mechanical Ventilation or Death Endpoint
time frame: Day 28
description: Progression to mechanical ventilation or death within the first 28 days of enrollment.
measure: 8-Point Ordinal Scale Endpoint
time frame: Day 29
description: Clinical efficacy of CCP relative to the control arm in adults hospitalized with COVID-19 according to clinical status as assessed by 8-point ordinal scale.
8 Point WHO Ordinal Scale of Clinical Status:
Uninfected (No clinical or virological evidence of infection) - 0
Ambulatory (No limitation of activities) - 1 Ambulatory (Limitation of Activities) - 2
Hospitalized Mild Disease (Hospitalized, no oxygen therapy) - 3 Hospitalized Mild Disease (Oxygen by mask or nasal prongs) - 4
Hospitalized Severe Disease (Non-invasive ventilation or high flow oxygen) - 5 Hospitalized Severe Disease (Intubation and mechanical ventilation) - 6 Hospitalized Severe Disease (Ventilation + Additional organ support (pressors, RRT, ECMO)) - 7
Dead (Death) - 8
arm group label: COVID-19 Convalescent Plasma
arm group type: Experimental
description: Subjects in the COVID-19 convalescent plasma group will receive a single infusion of 250 ml anti-SARS-CoV-2 convalescent fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.
arm group label: Placebo
arm group type: Placebo Comparator
description: Subjects in the placebo group will receive a single infusion of 250 ml of standard fresh frozen plasma, ABO compatible with the patient, within 24 hours of randomization.
intervention type: Biological
intervention name: COVID-19 Convalescent Plasma (CCP)
description: COVID-19 Convalescent Plasma (CCP) is a form of passive antibody therapy that involves the administration of anti-SARS-CoV-2 antibodies to a susceptible individual for the purpose of preventing or treating the infectious disease it causes. Convalescent plasma for this trial will be obtained from Vitalant (or American Red Cross if necessary). Patients identified as having recovered from COVID-19 will serve as potential donors. Potential donors will be screened using an anti-SARS-CoV-2 serologic assay and antibody levels will be determined.
arm group label: COVID-19 Convalescent Plasma
intervention type: Biological
intervention name: Placebo
description: Standard plasma will be obtained from Vitalant (or American Red Cross if necessary) and will be either collected prior to 12/1/2019 or tested and confirmed to be negative for anti-SARS-CoV-2.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Priscilla Hsue, MD
role: Principal Investigator
affiliation: University of California, San Francisco
last name: Annie Leutkemeyer, MD
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of California, San Francisco
investigator full name: Priscilla Hsue, MD
investigator title: Professor of Medicine
mesh term: COVID-19
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This study was limited by the small sample of hospitalized, hypoxic patients, limiting the generalizability of the results. Most participants were beyond 72 hours of symptom onset, the period when studies suggest CCP is most likely to be beneficial.
point of contact: 