<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/NCT04428021</url>
  </required_header>
  <id_info>
    <org_study_id>CS3/33</org_study_id>
    <nct_id>NCT04428021</nct_id>
  </id_info>
  <brief_title>Standard or Convalescent Plasma in Patients With Recent Onset of COVID-19 Respiratory Failure</brief_title>
  <acronym>PLACO-COVID</acronym>
  <official_title>Effectiveness of Adding Standard Plasma or COVID-19 Convalescent Plasma to Standard Treatment, Versus Standard Treatment Alone, in Patients With Recent Onset of COVID-19 Respiratory Failure. A Randomized, Three-arms, Phase 2 Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azienda Ospedaliera Città della Salute e della Scienza di Torino</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Azienda Ospedaliera Città della Salute e della Scienza di Torino</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To date no specific treatment has been proven to be effective for Severe Acute Respiratory&#xD;
      Syndrome Coronavirus 2 (SARS-Cov-2) infection. It is possible that convalescent plasma that&#xD;
      contains antibodies to SARS-Cov-2 might be effective against the progression of infection.&#xD;
      Promising results have been shown by preliminary data from China cases. The investigators&#xD;
      planned to compare effectiveness of adding COVID-19 convalescent plasma to standard therapy&#xD;
      protocol (STP) versus adding plasma donated in pre-COVID era versus STP alone in patient with&#xD;
      COVID-19 within 5 days from the onset of respiratory distress. STP at enrolment is the best&#xD;
      evidence based therapy approved for treatment of COVID patients by regional Health system&#xD;
      emergency committee.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      500-700 ml of Plasma will be collected by apheresis from COVID recovered donors showing the&#xD;
      presence of neutralizing antibodies to SARS-Cov-2 (anti-SARS-Cov-2). All plasma will be&#xD;
      screened for transmissible diseases according to italian law (Hepatitis B Virus,Hepatitis C&#xD;
      Virus, Human Immunodeficiency Virus 1-2, Syphilis) plus adjunctive screening for Hepatitis A&#xD;
      Virus and Hepatitis E Virus-RNA and Parvovirus B19-DNA as requested from Italian National&#xD;
      Blood Authority. Apheresis will be divided in two/three units (170-300 ml each), virus&#xD;
      inactivated with Riboflavin and ultraviolet light illumination technology and immediately&#xD;
      frozen and stored separately from other plasma bags.&#xD;
&#xD;
      Enrolled patients will be stratified according to severity of respiratory failure and&#xD;
      randomized in three arms: 1) Standard Therapy Protocol (STP), 2) Standard Therapy Protocol +&#xD;
      170-350 ml standard Plasma (SP) on day 1-3-5 after randomization, 3) Standard Therapy&#xD;
      Protocol + 170-350 ml COVID-19 Convalescent Plasma on day 1-3-5 after randomization.&#xD;
&#xD;
      The three therapeutic units of COVID-19 Convalescent plasma will be chosen in order to&#xD;
      minimize variations among patients in the total amount of infused SARS-Cov-2 antibodies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 15, 2020</start_date>
  <completion_date type="Actual">October 31, 2021</completion_date>
  <primary_completion_date type="Actual">March 31, 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>Three arms randomized trial, partially blinded</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
    <masking_description>Only the two experimental arms are masked. COVID-19 convalescent plasma (CP) and standard plasma (SP) will be masked and delivered to the wards in identical bags; a tag printed as &quot;PLASMA TRIAL&quot; will cover the actual name of the product</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>30-days survival</measure>
    <time_frame>30 days after randomization</time_frame>
    <description>Proportion of patients alive 30 days after randomization</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ventilator free survival</measure>
    <time_frame>30 days after randomization</time_frame>
    <description>Cumulative incidence of mechanical ventilation or death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>6-months survival</measure>
    <time_frame>6 months after randomization</time_frame>
    <description>Probability of being alive at 6 months after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of complications</measure>
    <time_frame>Within 12 months</time_frame>
    <description>Proportion of patients developing any serious medical or procedure related complications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Days in intensive care units (ICU)</measure>
    <time_frame>From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 12 months</time_frame>
    <description>Proportion of days spent in ICU on the total length of hospital stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Positivity for Immunoglobulin G to SARS-Cov-2</measure>
    <time_frame>On day 0, 2, 4, 6,10,14, 21, 28 after randomization and at date of discharge or death from any cause, whichever came first, assessed up to 12 months</time_frame>
    <description>Proportion of patients showing seroconversion to Immunoglobulin G (IgG) anti-SARS-Cov-2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance of viral load</measure>
    <time_frame>On day 0, 2, 4, 6,10,14, 21, 28 after randomization and at date of discharge or death from any cause, whichever came first, assessed up to 12 months</time_frame>
    <description>Proportion of patients showing viral clearance by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) on plasma and respiratory tract samples</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sequential Organ Failure Assessment (SOFA) score</measure>
    <time_frame>On day 0, 2, 4, 6, 10, 14, 28 after randomization and at date of discharge or death from any cause, whichever came first, assessed up to 12 months</time_frame>
    <description>Variations in SOFA Score (range 0-24; higher score mean a worse outcome)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Any variation from Standard Therapy Protocol</measure>
    <time_frame>From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed daily up to 2 months</time_frame>
    <description>Proportion of patients needing introduction of new drug or discontinuation of drug from standard therapy protocol</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">180</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Standard therapy protocol (STP)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>STP is defined as the best evidence based therapy approved for treatment of COVID-19 patients by Regional Health System emergency committee. STP could be updated during the trial.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>STP + Standard Plasma (SP)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>STP + 3 units on day 1-3-5 of Standard Plasma collected in pre-COVID era (January-September 2019)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>STP + COVID-19 Convalescent Plasma (CP)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>STP + 3 units on day 1-3-5 of COVID-19 Convalescent Plasma containing neutralizing SARS-Cov-2 antibodies</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard Therapy Protocol (STP)</intervention_name>
    <description>Standard Therapy Protocol according to the best evidence treatment recommended by the Regional Health System emergency committee</description>
    <arm_group_label>STP + COVID-19 Convalescent Plasma (CP)</arm_group_label>
    <arm_group_label>STP + Standard Plasma (SP)</arm_group_label>
    <arm_group_label>Standard therapy protocol (STP)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>STP + Standard Plasma (SP)</intervention_name>
    <description>Transfusion of three Standard Plasma Units (SP) on day 1,3,5 in addition to STP</description>
    <arm_group_label>STP + Standard Plasma (SP)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>STP + COVID-19 Convalescent Plasma (CP)</intervention_name>
    <description>Transfusion of three SARS-Cov-2 neutralizing antibodies positive Plasma Units (CP) on day 1,3,5 in addition to STP</description>
    <arm_group_label>STP + COVID-19 Convalescent Plasma (CP)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed SARS-Cov-2 diagnosis by RT-PCR on nasopharyngeal swab or on bronchoalveolar&#xD;
             lavage&#xD;
&#xD;
          -  Respiratory failure onset or progression within 5 days&#xD;
&#xD;
          -  Signed Informed Consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Previous severe reactions to plasma transfusion&#xD;
&#xD;
          -  Unavailability of blood group compatible COVID-19 convalescent plasma&#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>Paola Maria Manzini, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>AO Città della salute e della scienza di Torino</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>AO Città della salute e della scienza di Torino</name>
      <address>
        <city>Torino</city>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>June 7, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>February 21, 2022</last_update_submitted>
  <last_update_submitted_qc>February 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Azienda Ospedaliera Città della Salute e della Scienza di Torino</investigator_affiliation>
    <investigator_full_name>Paola Maria Manzini</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Respiratory Insufficiency</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All Individual Participant Data requests should be submitted to the corresponding author for consideration. Access to deidentified participant data may be granted following review, after the publication of major results</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>Data will be available after 12 months from study ending and for the following 5 years</ipd_time_frame>
    <ipd_access_criteria>Data requests should be submitted to the corresponding author for consideration.</ipd_access_criteria>
  </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/NCT04428021
org study id: CS3/33
nct id: NCT04428021
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
To date no specific treatment has been proven to be effective for Severe Acute Respiratory
      Syndrome Coronavirus 2 (SARS-Cov-2) infection. It is possible that convalescent plasma that
      contains antibodies to SARS-Cov-2 might be effective against the progression of infection.
      Promising results have been shown by preliminary data from China cases. The investigators
      planned to compare effectiveness of adding COVID-19 convalescent plasma to standard therapy
      protocol (STP) versus adding plasma donated in pre-COVID era versus STP alone in patient with
      COVID-19 within 5 days from the onset of respiratory distress. STP at enrolment is the best
      evidence based therapy approved for treatment of COVID patients by regional Health system
      emergency committee.
500-700 ml of Plasma will be collected by apheresis from COVID recovered donors showing the
      presence of neutralizing antibodies to SARS-Cov-2 (anti-SARS-Cov-2). All plasma will be
      screened for transmissible diseases according to italian law (Hepatitis B Virus,Hepatitis C
      Virus, Human Immunodeficiency Virus 1-2, Syphilis) plus adjunctive screening for Hepatitis A
      Virus and Hepatitis E Virus-RNA and Parvovirus B19-DNA as requested from Italian National
      Blood Authority. Apheresis will be divided in two/three units (170-300 ml each), virus
      inactivated with Riboflavin and ultraviolet light illumination technology and immediately
      frozen and stored separately from other plasma bags.

      Enrolled patients will be stratified according to severity of respiratory failure and
      randomized in three arms: 1) Standard Therapy Protocol (STP), 2) Standard Therapy Protocol +
      170-350 ml standard Plasma (SP) on day 1-3-5 after randomization, 3) Standard Therapy
      Protocol + 170-350 ml COVID-19 Convalescent Plasma on day 1-3-5 after randomization.

      The three therapeutic units of COVID-19 Convalescent plasma will be chosen in order to
      minimize variations among patients in the total amount of infused SARS-Cov-2 antibodies.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Three arms randomized trial, partially blinded
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
masking description: Only the two experimental arms are masked. COVID-19 convalescent plasma (CP) and standard plasma (SP) will be masked and delivered to the wards in identical bags; a tag printed as "PLASMA TRIAL" will cover the actual name of the product
measure: 30-days survival
time frame: 30 days after randomization
description: Proportion of patients alive 30 days after randomization
measure: Ventilator free survival
time frame: 30 days after randomization
description: Cumulative incidence of mechanical ventilation or death
measure: 6-months survival
time frame: 6 months after randomization
description: Probability of being alive at 6 months after randomization
measure: Incidence of complications
time frame: Within 12 months
description: Proportion of patients developing any serious medical or procedure related complications
measure: Days in intensive care units (ICU)
time frame: From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed up to 12 months
description: Proportion of days spent in ICU on the total length of hospital stay
measure: Positivity for Immunoglobulin G to SARS-Cov-2
time frame: On day 0, 2, 4, 6,10,14, 21, 28 after randomization and at date of discharge or death from any cause, whichever came first, assessed up to 12 months
description: Proportion of patients showing seroconversion to Immunoglobulin G (IgG) anti-SARS-Cov-2
measure: Clearance of viral load
time frame: On day 0, 2, 4, 6,10,14, 21, 28 after randomization and at date of discharge or death from any cause, whichever came first, assessed up to 12 months
description: Proportion of patients showing viral clearance by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) on plasma and respiratory tract samples
measure: Sequential Organ Failure Assessment (SOFA) score
time frame: On day 0, 2, 4, 6, 10, 14, 28 after randomization and at date of discharge or death from any cause, whichever came first, assessed up to 12 months
description: Variations in SOFA Score (range 0-24; higher score mean a worse outcome)
measure: Any variation from Standard Therapy Protocol
time frame: From date of randomization until the date of discharge or date of death from any cause, whichever came first, assessed daily up to 2 months
description: Proportion of patients needing introduction of new drug or discontinuation of drug from standard therapy protocol
arm group label: Standard therapy protocol (STP)
arm group type: Active Comparator
description: STP is defined as the best evidence based therapy approved for treatment of COVID-19 patients by Regional Health System emergency committee. STP could be updated during the trial.
arm group label: STP + Standard Plasma (SP)
arm group type: Experimental
description: STP + 3 units on day 1-3-5 of Standard Plasma collected in pre-COVID era (January-September 2019)
arm group label: STP + COVID-19 Convalescent Plasma (CP)
arm group type: Experimental
description: STP + 3 units on day 1-3-5 of COVID-19 Convalescent Plasma containing neutralizing SARS-Cov-2 antibodies
intervention type: Drug
intervention name: Standard Therapy Protocol (STP)
description: Standard Therapy Protocol according to the best evidence treatment recommended by the Regional Health System emergency committee
arm group label: STP + COVID-19 Convalescent Plasma (CP)
arm group label: STP + Standard Plasma (SP)
arm group label: Standard therapy protocol (STP)
intervention type: Other
intervention name: STP + Standard Plasma (SP)
description: Transfusion of three Standard Plasma Units (SP) on day 1,3,5 in addition to STP
arm group label: STP + Standard Plasma (SP)
intervention type: Other
intervention name: STP + COVID-19 Convalescent Plasma (CP)
description: Transfusion of three SARS-Cov-2 neutralizing antibodies positive Plasma Units (CP) on day 1,3,5 in addition to STP
arm group label: STP + COVID-19 Convalescent Plasma (CP)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paola Maria Manzini, MD
role: Principal Investigator
affiliation: AO Città della salute e della scienza di Torino
facility: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: Azienda Ospedaliera Città della Salute e della Scienza di Torino
investigator full name: Paola Maria Manzini
investigator title: Principal Investigator
mesh term: COVID-19
mesh term: Respiratory Insufficiency
sharing ipd: Yes
ipd description: All Individual Participant Data requests should be submitted to the corresponding author for consideration. Access to deidentified participant data may be granted following review, after the publication of major results
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Analytic Code
ipd time frame: Data will be available after 12 months from study ending and for the following 5 years
ipd access criteria: Data requests should be submitted to the corresponding author for consideration.