<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/NCT04442191</url>
  </required_header>
  <id_info>
    <org_study_id>2020-0441</org_study_id>
    <nct_id>NCT04442191</nct_id>
  </id_info>
  <brief_title>Convalescent Plasma as a Possible Treatment for COVID-19</brief_title>
  <official_title>Infusion of Convalescent Plasma for the Treatment of Patients Infected With Severe Acute Respiratory Syndrome-Coronavirus-2 (COVID-19): A Double-blinded, Placebo-controlled, Proof-of-concept Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Illinois at Chicago</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Illinois at Chicago</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>
      Patients who are ill with COVID-19 may benefit from receiving convalescent plasma infusions&#xD;
      containing antibodies from donors who have recovered from the disease and are proven to no&#xD;
      longer be infected. Given the current public health emergency due to COVID-19, the FDA has&#xD;
      recently fast-tracked the use of convalescent plasma. The purpose for this study is to assess&#xD;
      if convalescent plasma collected from donors previously infected with Severe Acute&#xD;
      Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, can provide&#xD;
      clinical benefit to those acutely ill with the virus and to evaluate if such treatment is&#xD;
      safe.&#xD;
&#xD;
      There will be two arms in the interventional study, where subjects will either be treated&#xD;
      with convalescent plasma or fresh frozen plasma in a randomized and blinded manner. As an&#xD;
      additional comparison, the clinical course of subjects enrolled during the period of the&#xD;
      study who do not receive an alternative treatment for COVID-19 will be assessed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Design and Procedures - Comparison group (no-treatment control)&#xD;
&#xD;
        1. Subjects will be identified by reviewing a REDCap database containing the list of all&#xD;
           patients at the University of Illinois at Chicago Hospital (UIC) who were tested for&#xD;
           COVID-19. Using these data, the investigators will identify those subjects who are &gt;40&#xD;
           years old, were admitted to the hospital during the period of the study, otherwise met&#xD;
           all of the inclusion and exclusion criteria for the infusion arm of the study but were&#xD;
           not enrolled and did not receive any medications for treatment of COVID-19 (were treated&#xD;
           with only supportive care).&#xD;
&#xD;
        2. Clinical data from the hospital admissions of these subjects will be entered into a&#xD;
           REDCap database. The same clinical information captured for subjects who underwent&#xD;
           transfusion (vital signs, oxygen status, etc.) will be entered into this database.&#xD;
&#xD;
      Study Design and Procedures - Intervention arms Screening Visit&#xD;
&#xD;
        1. Patients admitted to UIC Hospital and meeting the inclusion criteria will be enrolled&#xD;
           after documentation of informed consent.&#xD;
&#xD;
        2. Enrolled subjects will answer a symptom screen, undergo a physical exam, and have&#xD;
           clinical data extracted from their chart (including medical history, demographic&#xD;
           information, vital signs and documentation of oxygen requirement).&#xD;
&#xD;
        3. Women of childbearing age will be asked if there is a chance that they might be&#xD;
           pregnant, if they are currently breastfeeding, and if they are planning to become&#xD;
           pregnant.&#xD;
&#xD;
        4. Blood will be drawn for a Complete Blood Count (CBC) and blood type and screen, and a&#xD;
           sample of blood will be stored for research purposes.&#xD;
&#xD;
        5. Nasopharyngeal and/or oropharyngeal swabs will be collected for Reverse&#xD;
           Transcriptase-Polymerase Chain Reaction (RT-PCR) testing.&#xD;
&#xD;
        6. A study investigator will ask the patient's primary team if they are planning on&#xD;
           treating the patient with Remdesivir. If the patient qualifies for this medication, the&#xD;
           study investigator will monitor the patient's chart and work with the patient's nurse to&#xD;
           ensure that the first convalescent plasma infusion and first dose of Remdesivir are&#xD;
           given within 24 hours of each other.&#xD;
&#xD;
      Study Design and Procedures - Transfusion Visits (Study days 0 and 1) Note - the first&#xD;
      transfusion visit may be done on the same day as the screening visit if time permits,&#xD;
      otherwise it will be done the following day. Items 1 and 2 will only be performed for the&#xD;
      first transfusion visit if the visit occurs the day after the screening visit.&#xD;
&#xD;
        1. The patient's clinical status, oxygen requirement, vital signs, and physical exam will&#xD;
           be extracted from their clinical chart. Extracted information will include:&#xD;
&#xD;
             1. imaging: chest X-ray or chest CT results&#xD;
&#xD;
             2. labs: CBC with differential, C-Reactive Protein (CRP), alanine aminotransferase&#xD;
                (ALT), aspartate aminotransferase (AST), total bilirubin, creatinine.&#xD;
&#xD;
             3. Demographic and medical information: history of present infection (length of&#xD;
                symptoms prior to presentation, etc.)&#xD;
&#xD;
        2. Participants will be asked a symptom questionnaire.&#xD;
&#xD;
        3. Randomization to convalescent plasma or fresh frozen plasma will be 1:1. Randomization&#xD;
           will be conducted by a physician not involved in the study and using pre-prepared lists&#xD;
           with random permuted blocks of varying sizes. This physician will hand-deliver an order&#xD;
           sheet for either convalescent or fresh frozen plasma to the blood bank (this way no&#xD;
           orders that could potentially unblind study personnel will be in participants' charts).&#xD;
&#xD;
        4. The blood bank technical staff will select either two compatible blood-type&#xD;
           non-therapeutic units of plasma or two compatible units of convalescent plasma,&#xD;
           depending on which group the patient has been randomized to.&#xD;
&#xD;
        5. If the blood bank does not have any product of that patient's blood type, investigators&#xD;
           will not be able to have the subject complete the remainder of the study. However, the&#xD;
           investigators will keep the information about the participant's blood type in the study&#xD;
           database. Then, in the event that plasma of the appropriate blood type is obtained,&#xD;
           study investigators may contact participants to find out if they are still interested in&#xD;
           being part of the study.&#xD;
&#xD;
        6. The blood product will be delivered to the floor and the participant's nurse will infuse&#xD;
           and document plasma administration following UIC Hospital policy &quot;TX 5.03.&quot; Study&#xD;
           subjects will receive 1 unit of plasma the first day, with the second unit being given&#xD;
           the next day.&#xD;
&#xD;
        7. Once the blood product has been hung, the patient's nurse will place it in a bag that&#xD;
           will prevent the patient or physician's taking care of the patient from seeing whether&#xD;
           the unit is regular frozen plasma or convalescent plasma. The nurse will be under&#xD;
           instructions not to convey information about which type of plasma was used to the study&#xD;
           team.&#xD;
&#xD;
        8. The nurse will be instructed to stop the transfusion while a small sample of plasma&#xD;
           remains in the bag. The bag will then be sent back to the blood bank (this is usual&#xD;
           protocol for blood products), and remaining plasma will be emptied into a storage&#xD;
           container, labeled with the patient's study identification number, and frozen for later&#xD;
           use for research purposes.&#xD;
&#xD;
        9. If a transfusion reaction occurs the transfusion will be stopped and reported to the&#xD;
           blood bank as stated in UIC Hospital policy &quot;TX 5.03.&quot;&#xD;
&#xD;
      Study Design and Procedures - Post-infusion monitoring&#xD;
&#xD;
        1. Post-transfusion clinical data will be collected from electronic medical record daily&#xD;
           for days 2-8 following the first transfusion (or until the participant is discharged if&#xD;
           they are discharged prior to 8 days following transfusion). This information includes:&#xD;
&#xD;
             1. vital signs: temperature, blood pressure, respiratory rate, pulse&#xD;
&#xD;
             2. symptoms: cough, dyspnea, shortness of breath&#xD;
&#xD;
             3. oxygenation: oxygen saturation, supplemental oxygen requirement, supplemental&#xD;
                oxygen method (e.g., ventilator, nasal canula, prone positioning, etc.)&#xD;
&#xD;
             4. imaging: chest X-ray or chest CT results&#xD;
&#xD;
             5. labs: CBC with differential, CRP, ALT, AST, total bilirubin, creatinine (and&#xD;
                whether or not the patient has required renal support)&#xD;
&#xD;
             6. medications: antibiotics and anti-viral medications, neuromuscular blocking agents,&#xD;
                vasopressors&#xD;
&#xD;
             7. location: intensive care unit, discharged, regular hospital bed&#xD;
&#xD;
        2. The participant will have a swab sample for SARS-CoV-2 RT-PCR collected daily for days&#xD;
           2-8 following the first transfusion (or as many days as they are admitted if they are&#xD;
           discharged prior to 8 days following the first transfusion) and on day 14 following&#xD;
           plasma infusion.&#xD;
&#xD;
           Participants will also have blood drawn on days 2, 4, and 8 following the first plasma&#xD;
           infusion for measurement of antibody titers to SARS-CoV-2 (if they are discharged prior&#xD;
           to day 4 or 8 they will not undergo that day's blood draw).&#xD;
&#xD;
        3. If the patient is discharged prior to 14-days following infusion of plasma, they will be&#xD;
           asked to return to Project Wish on day 14 post- infusion of plasma for a blood draw (for&#xD;
           antibody titers), a nasopharyngeal and/or oropharyngeal swab (for RT-PCR testing) and to&#xD;
           answer a short symptom questionnaire.&#xD;
&#xD;
        4. The patient will be contacted by telephone (if discharged) at 28-days following plasma&#xD;
           infusion and will be asked a symptom questionnaire. If they remain in the hospital at&#xD;
           this time point, they will be asked this questionnaire (if capable) and will have&#xD;
           information regarding their clinical condition extracted from their chart.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 5, 2020</start_date>
  <completion_date type="Anticipated">May 5, 2021</completion_date>
  <primary_completion_date type="Anticipated">May 5, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>The patient's nurse will be instructed to place the blood product in a paper bag so the label on the product is not visible to the study physicians or to the patient.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Oxygen supplementation</measure>
    <time_frame>8 days</time_frame>
    <description>The primary endpoint will be clinical response at 8 days, defined as no need for oxygen supplementation for the previous 24 hours.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>28-day and in-hospital mortality rate</measure>
    <time_frame>28 days</time_frame>
    <description>Mortality rate during the 28 days of follow-up and during the subjects' initial hospital stays</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants transferred to the Intensive Care Unit (ICU)</measure>
    <time_frame>28 days</time_frame>
    <description>Transfer to an ICU bed during the 28 days following study enrollment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants intubated</measure>
    <time_frame>28 days</time_frame>
    <description>Intubation within the 28 days following study enrollment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay in days</measure>
    <time_frame>28 days</time_frame>
    <description>Number of days admitted to the hospital during the 28-day follow-up period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Type of respiratory support</measure>
    <time_frame>28 days</time_frame>
    <description>Type of respiratory support required during the 28-day follow-up period: intubation, high-flow oxygen by nasal canula, nasal canula</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-reactive Protein (CRP)</measure>
    <time_frame>28 days</time_frame>
    <description>Change in CRP following treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lymphocyte count</measure>
    <time_frame>28 days</time_frame>
    <description>Change in lymphocyte count following treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length or respiratory support required, in days</measure>
    <time_frame>28 days</time_frame>
    <description>Number of days respiratory support is required</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lactate dehydrogenase (LDH)</measure>
    <time_frame>28 days</time_frame>
    <description>Change in LDH following treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ferritin</measure>
    <time_frame>28 days</time_frame>
    <description>Change in Ferritin level following treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>D-Dimer</measure>
    <time_frame>28 days</time_frame>
    <description>Change in D-Dimer level following treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>White Blood Cell (WBC) Count</measure>
    <time_frame>28 days</time_frame>
    <description>Change in WBC count following treatment</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Safety endpoint: Severe transfusion reaction</measure>
    <time_frame>6 hours following transfusion</time_frame>
    <description>Severe transfusion reaction will be defined as having any of the following occur within 6 hours of the infusion of blood product and not attributable to the underlying disease: 1) an increase of 2 L/minutes or more in supplemental oxygen requirement compared to the baseline requirement before transfusion, 2) oxygen saturations &lt;93% despite oxygen via nasal canula, or 3) need for transfer to the ICU.</description>
  </other_outcome>
  <other_outcome>
    <measure>Safety endpoint two: adverse events</measure>
    <time_frame>24 hours following transfusion</time_frame>
    <description>Cumulative incidence of adverse events during the study period: transfusion reaction (fever, rash), transfusion related acute lung injury (TRALI), transfusion associated circulatory overload (TACO), transfusion related infection.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Convalescent plasma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This study will utilize convalescent plasma from donors recovered from infection with SARS-CoV-2 (which causes COVID-19) with neutralizing antibody titers &gt;1:64.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo utilized in this study will include Fresh Frozen Plasma collected before the COVID-19 pandemic began. As an extra control, some of this plasma will be saved and tested for COVID-19 antibodies to ensure they are not present.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Convalescent plasma</intervention_name>
    <description>This study will use convalescent plasma collected from those who have previously had COVID-19 and have been shown to have cleared the infection and made antibodies against the virus.</description>
    <arm_group_label>Convalescent plasma</arm_group_label>
    <other_name>Fresh Frozen Plasma</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The placebo arm of this study will use fresh frozen plasma that presumably does not contain antibodies against COVID-19.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Fresh Frozen Plasma</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients 40 years-old and over who are admitted to the University of Illinois Hospital&#xD;
             (UIC) due to COVID-19&#xD;
&#xD;
          -  Positive oropharyngeal and/or nasopharyngeal swab test for SARS-CoV-2 by RT-PCR within&#xD;
             the preceding 72 hours (performed by University of Illinois Hospital Laboratories or,&#xD;
             if performed elsewhere, documented in the patient's UIC medical record)&#xD;
&#xD;
          -  Symptomatic infection with any of the following: fever, cough, dyspnea, or tachypnea &gt;&#xD;
             22 breaths/min&#xD;
&#xD;
          -  Need for supplemental oxygen, between 1-5 liters/minute by nasal canula, to maintain&#xD;
             O2 saturations &gt;92%&#xD;
&#xD;
          -  Consents to comply with all protocol requirements&#xD;
&#xD;
          -  Agrees to storage of specimens for future testing&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with known Immunoglobulin A deficiency (high risk of severe or fatal&#xD;
             anaphylactic reactions)&#xD;
&#xD;
          -  Patients who are on a ventilator&#xD;
&#xD;
          -  Patients with past history of severe transfusion reaction including&#xD;
             transfusion-related acute lung injury (TRALI) or anaphylaxis&#xD;
&#xD;
          -  Patients with a baseline requirement for supplemental oxygen due to chronic lung&#xD;
             disease or with known history of either moderate-to-severe asthma or emphysema.&#xD;
&#xD;
          -  Female subjects who report that they are pregnant or breastfeeding&#xD;
&#xD;
          -  Receipt of pooled immunoglobulin in the past 30 days&#xD;
&#xD;
          -  Patients must be willing to not take any another alternative experimental treatment&#xD;
             for COVID-19 from the time they undergo enrollment until the 28-day follow-up phone&#xD;
             call&#xD;
&#xD;
             •. Participants who are being treated with Remdesivir and have had their first dose of&#xD;
             Remdesivir greater than 24 hours prior to the time they will receive their first dose&#xD;
             of convalescent plasma&#xD;
&#xD;
          -  Patients with severe disease due to COVID-19, as manifested by a need for&#xD;
             vasopressors, and/or diagnosis of Acute Respiratory Distress Syndrome&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of Illinois at Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jesica A Herrick, MD, MS</last_name>
      <phone>312-996-1834</phone>
      <email>Christe5@uic.edu</email>
    </contact>
    <investigator>
      <last_name>Jesica A Herrick, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Richard Novak, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mahesh Patel, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sally Campbell-Lee, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>May 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 22, 2020</study_first_posted>
  <last_update_submitted>June 19, 2020</last_update_submitted>
  <last_update_submitted_qc>June 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Illinois at Chicago</investigator_affiliation>
    <investigator_full_name>Jesica Herrick</investigator_full_name>
    <investigator_title>Assistant Professor of Clinical Medicine</investigator_title>
  </responsible_party>
  <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>
  <!-- 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/NCT04442191
org study id: 2020-0441
nct id: NCT04442191
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Patients who are ill with COVID-19 may benefit from receiving convalescent plasma infusions
      containing antibodies from donors who have recovered from the disease and are proven to no
      longer be infected. Given the current public health emergency due to COVID-19, the FDA has
      recently fast-tracked the use of convalescent plasma. The purpose for this study is to assess
      if convalescent plasma collected from donors previously infected with Severe Acute
      Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, can provide
      clinical benefit to those acutely ill with the virus and to evaluate if such treatment is
      safe.

      There will be two arms in the interventional study, where subjects will either be treated
      with convalescent plasma or fresh frozen plasma in a randomized and blinded manner. As an
      additional comparison, the clinical course of subjects enrolled during the period of the
      study who do not receive an alternative treatment for COVID-19 will be assessed.
Study Design and Procedures - Comparison group (no-treatment control)

        1. Subjects will be identified by reviewing a REDCap database containing the list of all
           patients at the University of Illinois at Chicago Hospital (UIC) who were tested for
           COVID-19. Using these data, the investigators will identify those subjects who are >40
           years old, were admitted to the hospital during the period of the study, otherwise met
           all of the inclusion and exclusion criteria for the infusion arm of the study but were
           not enrolled and did not receive any medications for treatment of COVID-19 (were treated
           with only supportive care).

        2. Clinical data from the hospital admissions of these subjects will be entered into a
           REDCap database. The same clinical information captured for subjects who underwent
           transfusion (vital signs, oxygen status, etc.) will be entered into this database.

      Study Design and Procedures - Intervention arms Screening Visit

        1. Patients admitted to UIC Hospital and meeting the inclusion criteria will be enrolled
           after documentation of informed consent.

        2. Enrolled subjects will answer a symptom screen, undergo a physical exam, and have
           clinical data extracted from their chart (including medical history, demographic
           information, vital signs and documentation of oxygen requirement).

        3. Women of childbearing age will be asked if there is a chance that they might be
           pregnant, if they are currently breastfeeding, and if they are planning to become
           pregnant.

        4. Blood will be drawn for a Complete Blood Count (CBC) and blood type and screen, and a
           sample of blood will be stored for research purposes.

        5. Nasopharyngeal and/or oropharyngeal swabs will be collected for Reverse
           Transcriptase-Polymerase Chain Reaction (RT-PCR) testing.

        6. A study investigator will ask the patient's primary team if they are planning on
           treating the patient with Remdesivir. If the patient qualifies for this medication, the
           study investigator will monitor the patient's chart and work with the patient's nurse to
           ensure that the first convalescent plasma infusion and first dose of Remdesivir are
           given within 24 hours of each other.

      Study Design and Procedures - Transfusion Visits (Study days 0 and 1) Note - the first
      transfusion visit may be done on the same day as the screening visit if time permits,
      otherwise it will be done the following day. Items 1 and 2 will only be performed for the
      first transfusion visit if the visit occurs the day after the screening visit.

        1. The patient's clinical status, oxygen requirement, vital signs, and physical exam will
           be extracted from their clinical chart. Extracted information will include:

             1. imaging: chest X-ray or chest CT results

             2. labs: CBC with differential, C-Reactive Protein (CRP), alanine aminotransferase
                (ALT), aspartate aminotransferase (AST), total bilirubin, creatinine.

             3. Demographic and medical information: history of present infection (length of
                symptoms prior to presentation, etc.)

        2. Participants will be asked a symptom questionnaire.

        3. Randomization to convalescent plasma or fresh frozen plasma will be 1:1. Randomization
           will be conducted by a physician not involved in the study and using pre-prepared lists
           with random permuted blocks of varying sizes. This physician will hand-deliver an order
           sheet for either convalescent or fresh frozen plasma to the blood bank (this way no
           orders that could potentially unblind study personnel will be in participants' charts).

        4. The blood bank technical staff will select either two compatible blood-type
           non-therapeutic units of plasma or two compatible units of convalescent plasma,
           depending on which group the patient has been randomized to.

        5. If the blood bank does not have any product of that patient's blood type, investigators
           will not be able to have the subject complete the remainder of the study. However, the
           investigators will keep the information about the participant's blood type in the study
           database. Then, in the event that plasma of the appropriate blood type is obtained,
           study investigators may contact participants to find out if they are still interested in
           being part of the study.

        6. The blood product will be delivered to the floor and the participant's nurse will infuse
           and document plasma administration following UIC Hospital policy "TX 5.03." Study
           subjects will receive 1 unit of plasma the first day, with the second unit being given
           the next day.

        7. Once the blood product has been hung, the patient's nurse will place it in a bag that
           will prevent the patient or physician's taking care of the patient from seeing whether
           the unit is regular frozen plasma or convalescent plasma. The nurse will be under
           instructions not to convey information about which type of plasma was used to the study
           team.

        8. The nurse will be instructed to stop the transfusion while a small sample of plasma
           remains in the bag. The bag will then be sent back to the blood bank (this is usual
           protocol for blood products), and remaining plasma will be emptied into a storage
           container, labeled with the patient's study identification number, and frozen for later
           use for research purposes.

        9. If a transfusion reaction occurs the transfusion will be stopped and reported to the
           blood bank as stated in UIC Hospital policy "TX 5.03."

      Study Design and Procedures - Post-infusion monitoring

        1. Post-transfusion clinical data will be collected from electronic medical record daily
           for days 2-8 following the first transfusion (or until the participant is discharged if
           they are discharged prior to 8 days following transfusion). This information includes:

             1. vital signs: temperature, blood pressure, respiratory rate, pulse

             2. symptoms: cough, dyspnea, shortness of breath

             3. oxygenation: oxygen saturation, supplemental oxygen requirement, supplemental
                oxygen method (e.g., ventilator, nasal canula, prone positioning, etc.)

             4. imaging: chest X-ray or chest CT results

             5. labs: CBC with differential, CRP, ALT, AST, total bilirubin, creatinine (and
                whether or not the patient has required renal support)

             6. medications: antibiotics and anti-viral medications, neuromuscular blocking agents,
                vasopressors

             7. location: intensive care unit, discharged, regular hospital bed

        2. The participant will have a swab sample for SARS-CoV-2 RT-PCR collected daily for days
           2-8 following the first transfusion (or as many days as they are admitted if they are
           discharged prior to 8 days following the first transfusion) and on day 14 following
           plasma infusion.

           Participants will also have blood drawn on days 2, 4, and 8 following the first plasma
           infusion for measurement of antibody titers to SARS-CoV-2 (if they are discharged prior
           to day 4 or 8 they will not undergo that day's blood draw).

        3. If the patient is discharged prior to 14-days following infusion of plasma, they will be
           asked to return to Project Wish on day 14 post- infusion of plasma for a blood draw (for
           antibody titers), a nasopharyngeal and/or oropharyngeal swab (for RT-PCR testing) and to
           answer a short symptom questionnaire.

        4. The patient will be contacted by telephone (if discharged) at 28-days following plasma
           infusion and will be asked a symptom questionnaire. If they remain in the hospital at
           this time point, they will be asked this questionnaire (if capable) and will have
           information regarding their clinical condition extracted from their chart.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: The patient's nurse will be instructed to place the blood product in a paper bag so the label on the product is not visible to the study physicians or to the patient.
measure: Oxygen supplementation
time frame: 8 days
description: The primary endpoint will be clinical response at 8 days, defined as no need for oxygen supplementation for the previous 24 hours.
measure: 28-day and in-hospital mortality rate
time frame: 28 days
description: Mortality rate during the 28 days of follow-up and during the subjects' initial hospital stays
measure: Number of participants transferred to the Intensive Care Unit (ICU)
time frame: 28 days
description: Transfer to an ICU bed during the 28 days following study enrollment
measure: Number of participants intubated
time frame: 28 days
description: Intubation within the 28 days following study enrollment
measure: Length of hospital stay in days
time frame: 28 days
description: Number of days admitted to the hospital during the 28-day follow-up period
measure: Type of respiratory support
time frame: 28 days
description: Type of respiratory support required during the 28-day follow-up period: intubation, high-flow oxygen by nasal canula, nasal canula
measure: C-reactive Protein (CRP)
time frame: 28 days
description: Change in CRP following treatment
measure: Lymphocyte count
time frame: 28 days
description: Change in lymphocyte count following treatment
measure: Length or respiratory support required, in days
time frame: 28 days
description: Number of days respiratory support is required
measure: Lactate dehydrogenase (LDH)
time frame: 28 days
description: Change in LDH following treatment
measure: Ferritin
time frame: 28 days
description: Change in Ferritin level following treatment
measure: D-Dimer
time frame: 28 days
description: Change in D-Dimer level following treatment
measure: White Blood Cell (WBC) Count
time frame: 28 days
description: Change in WBC count following treatment
measure: Safety endpoint: Severe transfusion reaction
time frame: 6 hours following transfusion
description: Severe transfusion reaction will be defined as having any of the following occur within 6 hours of the infusion of blood product and not attributable to the underlying disease: 1) an increase of 2 L/minutes or more in supplemental oxygen requirement compared to the baseline requirement before transfusion, 2) oxygen saturations <93% despite oxygen via nasal canula, or 3) need for transfer to the ICU.
measure: Safety endpoint two: adverse events
time frame: 24 hours following transfusion
description: Cumulative incidence of adverse events during the study period: transfusion reaction (fever, rash), transfusion related acute lung injury (TRALI), transfusion associated circulatory overload (TACO), transfusion related infection.
arm group label: Convalescent plasma
arm group type: Experimental
description: This study will utilize convalescent plasma from donors recovered from infection with SARS-CoV-2 (which causes COVID-19) with neutralizing antibody titers >1:64.
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo utilized in this study will include Fresh Frozen Plasma collected before the COVID-19 pandemic began. As an extra control, some of this plasma will be saved and tested for COVID-19 antibodies to ensure they are not present.
intervention type: Biological
intervention name: Convalescent plasma
description: This study will use convalescent plasma collected from those who have previously had COVID-19 and have been shown to have cleared the infection and made antibodies against the virus.
arm group label: Convalescent plasma
other name: Fresh Frozen Plasma
intervention type: Biological
intervention name: Placebo
description: The placebo arm of this study will use fresh frozen plasma that presumably does not contain antibodies against COVID-19.
arm group label: Placebo
other name: Fresh Frozen Plasma
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Illinois at Chicago
investigator full name: Jesica Herrick
investigator title: Assistant Professor of Clinical Medicine
mesh term: COVID-19
sharing ipd: No