<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/NCT04479163</url>
  </required_header>
  <id_info>
    <org_study_id>FundacionINFANT-Plasma</org_study_id>
    <nct_id>NCT04479163</nct_id>
  </id_info>
  <brief_title>Prevention of Severe Covid-19 in Infected Elderly by Early Administration of Convalescent Plasma With High-titers of Antibody Against SARS-CoV2</brief_title>
  <official_title>Prevention of Severe Covid-19 in Infected Elderly by Early Administration of Convalescent Plasma With High-titers of Antibody Against SARS-CoV2.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundacion Infant</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fundacion Infant</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>
      Trial design. Randomized, double-blind, placebo-controlled trial in a catchment population of&#xD;
      2,020,860 age-appropriate subjects in the state of Buenos Aires and 235,000 in the city of&#xD;
      Buenos Aires.&#xD;
&#xD;
      Institutions. Hospitals San Juan de Dios, Simplemente Evita, Dr. Carlos Bocalandro, Evita&#xD;
      Pueblo, Sanatorio Antartida, Hospital Central de San Isidro, Clinica Olivos in the state of&#xD;
      Buenos Aires with 38 regional and town hospitals acting as referral centers, and Hospital&#xD;
      Militar Central, Sanatorio de Los Arcos, Hospital Universitario CEMIC, Sanatorio Sagrado&#xD;
      Corazon, Sanatorio Finochietto, Sanatorio Anchorena, Centro Gallego, and in the city of&#xD;
      Buenos Aires in Argentina.&#xD;
&#xD;
      Study population. Subjects &gt;= 75 years of age irrespective of presenting comorbidities or&#xD;
      between 65-74 years of age with at least one comorbidity (hypertension, diabetes, obesity,&#xD;
      chronic renal failure, and COPD) who experience the following signs and symptoms for less&#xD;
      than 48 hours at the time of screening for SARS CoV2 by RT-PCR: (a) a temperature &gt;=37.5°C&#xD;
      and/or unexplained sweating and/or chills and (b) at least one of the following: dry cough,&#xD;
      dyspnea, fatigue, myalgia, anorexia, sore throat, loss of taste and/or smell, rhinorrhea.&#xD;
      Subjects consenting to screening will be tested by&#xD;
      reverse-transcriptase-polymerase-chain-reaction (RT-PCR) for SARS-CoV-2 in a nasopharyngeal&#xD;
      and an oropharyngeal swab and invited to participate when RNA for the virus is detected.&#xD;
&#xD;
      Intervention. Eligible, consenting patients will be randomized using an electronic system to&#xD;
      receive 250 ml of convalescent plasma with an IgG titer against SARS-CoV2 spike (S) protein&#xD;
      &gt;1:1,000 (COVIDAR IgG, Insituto Leloir, Argentina) or placebo (normal saline 0.9%)&#xD;
      administered in a 1:1 ratio. Both treatment and placebo will be concealed using dark bags and&#xD;
      tape to cover the infusion line. Treatment will be administered &lt;72 hours from initiation of&#xD;
      symptoms. Subjects will be monitored for 12 hours after treatment for adverse events.&#xD;
&#xD;
      Clinical and laboratory monitoring. All participating subjects will be admitted to the&#xD;
      hospital upon enrollment. Twenty-four hours after completing the infusion, a sample of venous&#xD;
      blood (5 ml) will be obtained from all participants to measure anti-S IgG SARS-CoV2 in serum&#xD;
      (COVIDAR IgG, Leloir) and preserved at -20°C until completion of the study. Patient evolution&#xD;
      will be assessed daily by study physicians during hospitalization until day 25 and/or at home&#xD;
      until day 15, in the event of earlier discharge from the hospital. Study physicians will use&#xD;
      predesigned questionnaires to collect clinical information. An Independent Data Safety&#xD;
      Monitoring Board (DSMB) will supervise participating subjects during the study.&#xD;
&#xD;
      Endpoints. The primary endpoint of the trial is development of severe respiratory disease&#xD;
      defined as a respiratory rate (RR)&gt;30 and/or an O2 sat&lt;93% when breathing room air determined&#xD;
      using a predefined protocol. Three other clinical endpoints include (a) life threatening&#xD;
      respiratory disease, defined as need for 100% oxygen supplementation and/or non-invasive or&#xD;
      invasive ventilation and/or admission to intensive care; (b) critical systemic illness,&#xD;
      defined as respiratory failure (PaO2/FiO2 ≤ 200 mm Hg) and/or shock and/or multiorganic&#xD;
      distress syndrome; and (c) death.&#xD;
&#xD;
      Statistical analysis. The study is designed to have one interim analysis when the outcome&#xD;
      results for 50% of the subjects is obtained. The minimally clinically important difference&#xD;
      was set at a 40% relative reduction for an expected outcome rate of 50% in the control group&#xD;
      reduced to 30% in the intervention group. A total sample size of 210 subjects (105 per trial&#xD;
      arm) was estimated to have 80% power at a significance level (alpha) of 0.05 using a&#xD;
      two-sided z-test with continuity correction.&#xD;
&#xD;
      Ethical considerations. The trial has been approved by the institutional review boards of&#xD;
      participating institutions and the Central Ethics Committee of the state of Buenos Aires. The&#xD;
      study will be conducted in accordance with the principles of the Declaration of Helsinki and&#xD;
      the Good Clinical Practice guidelines of the International Conference on Harmonization.&#xD;
      Written informed consent will be obtained from all patients for screening and enrollment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 4, 2020</start_date>
  <completion_date type="Actual">October 25, 2020</completion_date>
  <primary_completion_date type="Actual">October 25, 2020</primary_completion_date>
  <phase>N/A</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Development of severe respiratory disease defined as a respiratory rate (RR)&gt;30 and/or an O2 sat&lt;93%</measure>
    <time_frame>From 12 hours post infusion to day 15 post infusion</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Life threatening respiratory disease</measure>
    <time_frame>From 12 hours post infusion to day 25 post infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Critical systemic illness, defined as respiratory failure</measure>
    <time_frame>From 12 hours post infusion to day 25 post infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death</measure>
    <time_frame>From 12 hours post infusion to day 25 post infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Combination of secondary outcomes #2 (Life threatening respiratory disease) and/or #3 (Critical systemic illness, defined as respiratory failure) and//or #4 (death)</measure>
    <time_frame>From 12 hours post infusion to day 25 post infusion</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of oxygen support requirement in patients with covid-19 due to saturation in ambient air &lt;93%.</measure>
    <time_frame>From 12 hours post infusion to day 25 post infusion</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">165</enrollment>
  <condition>COVID</condition>
  <arm_group>
    <arm_group_label>Plasma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Convalescent plasma with an IgG titer against SARS-CoV2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal Saline 0.9%</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Convalescent Plasma</intervention_name>
    <description>250 ml Convalescent plasma with an IgG titer against SARS CoV2</description>
    <arm_group_label>Plasma</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Normal Saline 0.9%</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        - Age ≥ 75 or age 65-74 with at least 1 of the following comorbidities: arterial&#xD;
        hypertension, diabetes, obesity, chronic obstructive pulmonary disease, heart disease,&#xD;
        chronic kidney disease&#xD;
&#xD;
          -  Last 48 hours: (A)Axillary temperature ≥ 37.5oC or febrile equivalent, combined with&#xD;
             (a) dry cough and/or (b) breathing difficulty and/or (c) odinophagia and/or (d)&#xD;
             anosmia/dysgeusia and/or (e) any of the following symptoms: fatigue, anorexia,&#xD;
             myalgias or rhinorrhea.&#xD;
&#xD;
          -  Confirmed diagnosis SARS-Cov2 by RT-PCR&#xD;
&#xD;
          -  Give Informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe respiratory disease&#xD;
&#xD;
          -  Cardiac insufficiency,&#xD;
&#xD;
          -  Chronic renal failure,&#xD;
&#xD;
          -  Primary hypogammaglobulinemias,&#xD;
&#xD;
          -  Myelodysplastic syndromes,&#xD;
&#xD;
          -  Chronic linfoproliferative syndromes,&#xD;
&#xD;
          -  Monoclonal gammapathies,&#xD;
&#xD;
          -  Known hypersensitibility,&#xD;
&#xD;
          -  Active cancer,&#xD;
&#xD;
          -  HIV, HBV or HCV infection,&#xD;
&#xD;
          -  Chronic administration of immunosuppressants,&#xD;
&#xD;
          -  Body transplant history,&#xD;
&#xD;
          -  Chronic liver disease, Chronic lung disease with oxygen requirement.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fernando P Polack, MD</last_name>
    <role>Study Director</role>
    <affiliation>Fundacion Infant</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital Militar Central</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <zip>1426</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CEMIC</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Investigacion Clinica OSECAC</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Gallego de Buenos Aires</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanatorio Anchorena</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanatorio de Los Arcos</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital &quot;Simplemente Evita&quot;</name>
      <address>
        <city>González Catán</city>
        <state>Buenos Aires</state>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Especializado de Agudos y Crónicos &quot;San Juan de Dios&quot;</name>
      <address>
        <city>La Plata</city>
        <state>Buenos Aires</state>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Olivos</name>
      <address>
        <city>Buenos Aires</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Central de San Isidro</name>
      <address>
        <city>Buenos Aires</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General de Agudos &quot;Dr. Carlos Bocalandro&quot;</name>
      <address>
        <city>Buenos Aires</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>July 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>December 19, 2020</last_update_submitted>
  <last_update_submitted_qc>December 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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/NCT04479163
org study id: FundacionINFANT-Plasma
nct id: NCT04479163
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Trial design. Randomized, double-blind, placebo-controlled trial in a catchment population of
      2,020,860 age-appropriate subjects in the state of Buenos Aires and 235,000 in the city of
      Buenos Aires.

      Institutions. Hospitals San Juan de Dios, Simplemente Evita, Dr. Carlos Bocalandro, Evita
      Pueblo, Sanatorio Antartida, Hospital Central de San Isidro, Clinica Olivos in the state of
      Buenos Aires with 38 regional and town hospitals acting as referral centers, and Hospital
      Militar Central, Sanatorio de Los Arcos, Hospital Universitario CEMIC, Sanatorio Sagrado
      Corazon, Sanatorio Finochietto, Sanatorio Anchorena, Centro Gallego, and in the city of
      Buenos Aires in Argentina.

      Study population. Subjects >= 75 years of age irrespective of presenting comorbidities or
      between 65-74 years of age with at least one comorbidity (hypertension, diabetes, obesity,
      chronic renal failure, and COPD) who experience the following signs and symptoms for less
      than 48 hours at the time of screening for SARS CoV2 by RT-PCR: (a) a temperature >=37.5°C
      and/or unexplained sweating and/or chills and (b) at least one of the following: dry cough,
      dyspnea, fatigue, myalgia, anorexia, sore throat, loss of taste and/or smell, rhinorrhea.
      Subjects consenting to screening will be tested by
      reverse-transcriptase-polymerase-chain-reaction (RT-PCR) for SARS-CoV-2 in a nasopharyngeal
      and an oropharyngeal swab and invited to participate when RNA for the virus is detected.

      Intervention. Eligible, consenting patients will be randomized using an electronic system to
      receive 250 ml of convalescent plasma with an IgG titer against SARS-CoV2 spike (S) protein
      >1:1,000 (COVIDAR IgG, Insituto Leloir, Argentina) or placebo (normal saline 0.9%)
      administered in a 1:1 ratio. Both treatment and placebo will be concealed using dark bags and
      tape to cover the infusion line. Treatment will be administered <72 hours from initiation of
      symptoms. Subjects will be monitored for 12 hours after treatment for adverse events.

      Clinical and laboratory monitoring. All participating subjects will be admitted to the
      hospital upon enrollment. Twenty-four hours after completing the infusion, a sample of venous
      blood (5 ml) will be obtained from all participants to measure anti-S IgG SARS-CoV2 in serum
      (COVIDAR IgG, Leloir) and preserved at -20°C until completion of the study. Patient evolution
      will be assessed daily by study physicians during hospitalization until day 25 and/or at home
      until day 15, in the event of earlier discharge from the hospital. Study physicians will use
      predesigned questionnaires to collect clinical information. An Independent Data Safety
      Monitoring Board (DSMB) will supervise participating subjects during the study.

      Endpoints. The primary endpoint of the trial is development of severe respiratory disease
      defined as a respiratory rate (RR)>30 and/or an O2 sat<93% when breathing room air determined
      using a predefined protocol. Three other clinical endpoints include (a) life threatening
      respiratory disease, defined as need for 100% oxygen supplementation and/or non-invasive or
      invasive ventilation and/or admission to intensive care; (b) critical systemic illness,
      defined as respiratory failure (PaO2/FiO2 ≤ 200 mm Hg) and/or shock and/or multiorganic
      distress syndrome; and (c) death.

      Statistical analysis. The study is designed to have one interim analysis when the outcome
      results for 50% of the subjects is obtained. The minimally clinically important difference
      was set at a 40% relative reduction for an expected outcome rate of 50% in the control group
      reduced to 30% in the intervention group. A total sample size of 210 subjects (105 per trial
      arm) was estimated to have 80% power at a significance level (alpha) of 0.05 using a
      two-sided z-test with continuity correction.

      Ethical considerations. The trial has been approved by the institutional review boards of
      participating institutions and the Central Ethics Committee of the state of Buenos Aires. The
      study will be conducted in accordance with the principles of the Declaration of Helsinki and
      the Good Clinical Practice guidelines of the International Conference on Harmonization.
      Written informed consent will be obtained from all patients for screening and enrollment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Development of severe respiratory disease defined as a respiratory rate (RR)>30 and/or an O2 sat<93%
time frame: From 12 hours post infusion to day 15 post infusion
measure: Life threatening respiratory disease
time frame: From 12 hours post infusion to day 25 post infusion
measure: Critical systemic illness, defined as respiratory failure
time frame: From 12 hours post infusion to day 25 post infusion
measure: Death
time frame: From 12 hours post infusion to day 25 post infusion
measure: Combination of secondary outcomes #2 (Life threatening respiratory disease) and/or #3 (Critical systemic illness, defined as respiratory failure) and//or #4 (death)
time frame: From 12 hours post infusion to day 25 post infusion
measure: Duration of oxygen support requirement in patients with covid-19 due to saturation in ambient air <93%.
time frame: From 12 hours post infusion to day 25 post infusion
arm group label: Plasma
arm group type: Experimental
description: Convalescent plasma with an IgG titer against SARS-CoV2
arm group label: Placebo
arm group type: Placebo Comparator
description: Normal Saline 0.9%
intervention type: Biological
intervention name: Convalescent Plasma
description: 250 ml Convalescent plasma with an IgG titer against SARS CoV2
arm group label: Plasma
intervention type: Other
intervention name: Placebo
description: Normal Saline 0.9%
arm group label: Placebo
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Fernando P Polack, MD
role: Study Director
affiliation: Fundacion Infant
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Argentina
responsible party type: Sponsor
sharing ipd: No