<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/NCT04480632</url>
  </required_header>
  <id_info>
    <org_study_id>CEI-2020-01200</org_study_id>
    <nct_id>NCT04480632</nct_id>
  </id_info>
  <brief_title>Therapeutic Plasmapheresis in Critically Ill Adult Patients With COVID-19 Confirmed Diagnosis</brief_title>
  <acronym>PLASMA</acronym>
  <official_title>Therapeutic Plasmapheresis in Critically Ill Adult Patients With COVID-19 Confirmed Diagnosis / Plasmaféresis terapéutica en Pacientes Adultos críticamente Enfermos Con diagnóstico Confirmado de COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundación Cardiovascular de Colombia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fundación Cardiovascular de Colombia</source>
  <oversight_info>
    <has_dmc>No</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>
      Introduction: The SARS-CoV-2 outbreak has left more than two million infected worldwide in&#xD;
      the first four months of COVID-19 epidemic. To date, there is no specific treatment for the&#xD;
      disease and in critically ill patients there is an additional challenge in controlling the&#xD;
      systemic inflammatory response, which is characterized by cytokine storm, alteration in&#xD;
      coagulation and endothelial activation in addition to infection. Strategies used in previous&#xD;
      viral epidemics, such as convalescent plasma, are therapeutic options to rescue, especially&#xD;
      in individuals with a critical presentation of the disease.&#xD;
&#xD;
      Aim: To establish clinical response of critically ill patients with COVID-19 who received&#xD;
      convalescent plasma from subjects recovered from SARS-CoV-2 during their stay in Intensive&#xD;
      Care Unit at Fundación Cardiovascular de Colombia (Hospital Internacional de Colombia).&#xD;
&#xD;
      Methodology: Quasi-experimental study (no randomization will be performed). Adult patients&#xD;
      who meet selection criteria will receive 500 ml of ABO compatible convalescent plasma,&#xD;
      obtained by apheresis from patients recovered from SARS-CoV-2 infection. The main outcome&#xD;
      will be in-hospital mortality at 30 days, while indication for ventilatory support&#xD;
      (intubation) and adverse events at thirty days will be evaluated as secondary outcomes,&#xD;
      compared to subjects receiving usual treatment for clinical sign and symptoms given the&#xD;
      absence of ABO compatible plasma units. A survival analysis will be performed using&#xD;
      Kaplan-Meier method and association strength will be reported using HR and 95% CI crude and&#xD;
      adjusted for confounding variables.&#xD;
&#xD;
      Expected results: It is expected to know the clinical and paraclinical response of patients&#xD;
      receiving convalescent plasma in our institution, as well as to establish their probability&#xD;
      of survival and its associated factors.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">August 1, 2020</start_date>
  <completion_date type="Anticipated">August 2022</completion_date>
  <primary_completion_date type="Anticipated">August 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Quasi-experimental and open-label intervention study. In this study, the application of convalescent plasma is considered as an intervention, but randomization will not be performed by investigators; one arm will be patients who received ABO compatible convalescent plasma and the comparison group will be those patients with intervention indication but without compatible ABO plasma units within the institution.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>In-hospital mortality</measure>
    <time_frame>30 days</time_frame>
    <description>In-hospital mortality after administration of ABO compatible convalescent plasma or indication (but not plasmapheresis for absence of compatible convalescent plasma) for comparison group</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of renal replacement therapy</measure>
    <time_frame>30 days</time_frame>
    <description>Number of patients with medical indication of hemodialysis or peritoneal dialysis for acute renal failure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidece of adverse events</measure>
    <time_frame>During tranfusion until 24 hours after.</time_frame>
    <description>Number of patients with Alergic reaction, Anaphylaxis, Severe thrombotic events, Transfusion-related acute lung injury (TRALI)], Transfusion-associated circulatory overload (TACO)], Antibody-Dependent Enhancement (ADE)]</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">44</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>ABO compatible convalescent plasma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A 500 ml dose of convalescent plasma (from a single donor or two 250 ml units from one or two donations) collected by apheresis will be administered. In case of plasma storage, plasma unit will be thawed following parameters of blood bank. Administration will take place slowly and over the course of four hours. When two 250 ml units are administered, second unit must be administered after the first unit in a period not exceeding 12 hours.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Usual care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Usual medical care for critically ill patients at ICU</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Convalescent plasma</intervention_name>
    <description>ABO compatible convalescent plasma obtained from from recovered COVID-19 patients</description>
    <arm_group_label>ABO compatible convalescent plasma</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age range: Over 18 years old&#xD;
&#xD;
          -  Patients with confirmed infection by COVID-19 (positive real-time PCR) in ICU with:&#xD;
&#xD;
          -  Respiratory failure receiving ventilatory support and high parameters&#xD;
&#xD;
          -  Severe pneumonia with rapid progression&#xD;
&#xD;
          -  Ability to sign informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Contraindication of plasma administration due to history of anaphylaxis during&#xD;
             transfusions&#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>Norma Serrano, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Research, development and innovation director</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Norma Serrano, MD</last_name>
    <phone>3102740099</phone>
    <email>normaserrano@fcv.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Claudia Colmenares, MD</last_name>
    <phone>3002090822</phone>
    <email>claudiacolmenares@fcv.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hospital Internacional de Colombia</name>
      <address>
        <city>Piedecuesta</city>
        <state>Santander</state>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Colombia</country>
  </location_countries>
  <reference>
    <citation>Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, Chan P, Wong KC, Leung CB, Cheng G. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005 Jan;24(1):44-6. doi: 10.1007/s10096-004-1271-9.</citation>
    <PMID>15616839</PMID>
  </reference>
  <reference>
    <citation>Hui DS. Severe acute respiratory syndrome (SARS): lessons learnt in Hong Kong. J Thorac Dis. 2013 Aug;5 Suppl 2(Suppl 2):S122-6. doi: 10.3978/j.issn.2072-1439.2013.06.18.</citation>
    <PMID>23977432</PMID>
  </reference>
  <reference>
    <citation>Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR; Convalescent Plasma Study Group. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 2015 Jan 1;211(1):80-90. doi: 10.1093/infdis/jiu396. Epub 2014 Jul 16.</citation>
    <PMID>25030060</PMID>
  </reference>
  <reference>
    <citation>Keith P, Day M, Perkins L, Moyer L, Hewitt K, Wells A. A novel treatment approach to the novel coronavirus: an argument for the use of therapeutic plasma exchange for fulminant COVID-19. Crit Care. 2020 Apr 2;24(1):128. doi: 10.1186/s13054-020-2836-4. No abstract available.</citation>
    <PMID>32241301</PMID>
  </reference>
  <reference>
    <citation>Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Apr 28;323(16):1582-1589. doi: 10.1001/jama.2020.4783.</citation>
    <PMID>32219428</PMID>
  </reference>
  <reference>
    <citation>Zhang B, Liu S, Tan T, Huang W, Dong Y, Chen L, Chen Q, Zhang L, Zhong Q, Zhang X, Zou Y, Zhang S. Treatment With Convalescent Plasma for Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Chest. 2020 Jul;158(1):e9-e13. doi: 10.1016/j.chest.2020.03.039. Epub 2020 Mar 31.</citation>
    <PMID>32243945</PMID>
  </reference>
  <reference>
    <citation>Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, Zhou M, Chen L, Meng S, Hu Y, Peng C, Yuan M, Huang J, Wang Z, Yu J, Gao X, Wang D, Yu X, Li L, Zhang J, Wu X, Li B, Xu Y, Chen W, Peng Y, Hu Y, Lin L, Liu X, Huang S, Zhou Z, Zhang L, Wang Y, Zhang Z, Deng K, Xia Z, Gong Q, Zhang W, Zheng X, Liu Y, Yang H, Zhou D, Yu D, Hou J, Shi Z, Chen S, Chen Z, Zhang X, Yang X. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. 2020 Apr 28;117(17):9490-9496. doi: 10.1073/pnas.2004168117. Epub 2020 Apr 6.</citation>
    <PMID>32253318</PMID>
  </reference>
  <reference>
    <citation>Ahn JY, Sohn Y, Lee SH, Cho Y, Hyun JH, Baek YJ, Jeong SJ, Kim JH, Ku NS, Yeom JS, Roh J, Ahn MY, Chin BS, Kim YS, Lee H, Yong D, Kim HO, Kim S, Choi JY. Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea. J Korean Med Sci. 2020 Apr 13;35(14):e149. doi: 10.3346/jkms.2020.35.e149.</citation>
    <PMID>32281317</PMID>
  </reference>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 17, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>July 20, 2020</last_update_submitted>
  <last_update_submitted_qc>July 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>Convalescent plasma</keyword>
  <keyword>Intensive Care Unit</keyword>
  <keyword>Critical illness</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>
  <!-- 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/NCT04480632
org study id: CEI-2020-01200
nct id: NCT04480632
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Introduction: The SARS-CoV-2 outbreak has left more than two million infected worldwide in
      the first four months of COVID-19 epidemic. To date, there is no specific treatment for the
      disease and in critically ill patients there is an additional challenge in controlling the
      systemic inflammatory response, which is characterized by cytokine storm, alteration in
      coagulation and endothelial activation in addition to infection. Strategies used in previous
      viral epidemics, such as convalescent plasma, are therapeutic options to rescue, especially
      in individuals with a critical presentation of the disease.

      Aim: To establish clinical response of critically ill patients with COVID-19 who received
      convalescent plasma from subjects recovered from SARS-CoV-2 during their stay in Intensive
      Care Unit at Fundación Cardiovascular de Colombia (Hospital Internacional de Colombia).

      Methodology: Quasi-experimental study (no randomization will be performed). Adult patients
      who meet selection criteria will receive 500 ml of ABO compatible convalescent plasma,
      obtained by apheresis from patients recovered from SARS-CoV-2 infection. The main outcome
      will be in-hospital mortality at 30 days, while indication for ventilatory support
      (intubation) and adverse events at thirty days will be evaluated as secondary outcomes,
      compared to subjects receiving usual treatment for clinical sign and symptoms given the
      absence of ABO compatible plasma units. A survival analysis will be performed using
      Kaplan-Meier method and association strength will be reported using HR and 95% CI crude and
      adjusted for confounding variables.

      Expected results: It is expected to know the clinical and paraclinical response of patients
      receiving convalescent plasma in our institution, as well as to establish their probability
      of survival and its associated factors.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Quasi-experimental and open-label intervention study. In this study, the application of convalescent plasma is considered as an intervention, but randomization will not be performed by investigators; one arm will be patients who received ABO compatible convalescent plasma and the comparison group will be those patients with intervention indication but without compatible ABO plasma units within the institution.
primary purpose: Treatment
masking: None (Open Label)
measure: In-hospital mortality
time frame: 30 days
description: In-hospital mortality after administration of ABO compatible convalescent plasma or indication (but not plasmapheresis for absence of compatible convalescent plasma) for comparison group
measure: Incidence of renal replacement therapy
time frame: 30 days
description: Number of patients with medical indication of hemodialysis or peritoneal dialysis for acute renal failure
measure: Incidece of adverse events
time frame: During tranfusion until 24 hours after.
description: Number of patients with Alergic reaction, Anaphylaxis, Severe thrombotic events, Transfusion-related acute lung injury (TRALI)], Transfusion-associated circulatory overload (TACO)], Antibody-Dependent Enhancement (ADE)]
arm group label: ABO compatible convalescent plasma
arm group type: Experimental
description: A 500 ml dose of convalescent plasma (from a single donor or two 250 ml units from one or two donations) collected by apheresis will be administered. In case of plasma storage, plasma unit will be thawed following parameters of blood bank. Administration will take place slowly and over the course of four hours. When two 250 ml units are administered, second unit must be administered after the first unit in a period not exceeding 12 hours.
arm group label: Usual care
arm group type: No Intervention
description: Usual medical care for critically ill patients at ICU
intervention type: Biological
intervention name: Convalescent plasma
description: ABO compatible convalescent plasma obtained from from recovered COVID-19 patients
arm group label: ABO compatible convalescent plasma
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Norma Serrano, MD
role: Principal Investigator
affiliation: Research, development and innovation director
last name: Norma Serrano, MD
phone: 3102740099
email: normaserrano@fcv.org
last name: Claudia Colmenares, MD
phone: 3002090822
email: claudiacolmenares@fcv.org
facility: 
country: Colombia
citation: Cheng Y, Wong R, Soo YO, Wong WS, Lee CK, Ng MH, Chan P, Wong KC, Leung CB, Cheng G. Use of convalescent plasma therapy in SARS patients in Hong Kong. Eur J Clin Microbiol Infect Dis. 2005 Jan;24(1):44-6. doi: 10.1007/s10096-004-1271-9.
PMID: 15616839
citation: Hui DS. Severe acute respiratory syndrome (SARS): lessons learnt in Hong Kong. J Thorac Dis. 2013 Aug;5 Suppl 2(Suppl 2):S122-6. doi: 10.3978/j.issn.2072-1439.2013.06.18.
PMID: 23977432
citation: Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR; Convalescent Plasma Study Group. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis. 2015 Jan 1;211(1):80-90. doi: 10.1093/infdis/jiu396. Epub 2014 Jul 16.
PMID: 25030060
citation: Keith P, Day M, Perkins L, Moyer L, Hewitt K, Wells A. A novel treatment approach to the novel coronavirus: an argument for the use of therapeutic plasma exchange for fulminant COVID-19. Crit Care. 2020 Apr 2;24(1):128. doi: 10.1186/s13054-020-2836-4. No abstract available.
PMID: 32241301
citation: Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma. JAMA. 2020 Apr 28;323(16):1582-1589. doi: 10.1001/jama.2020.4783.
PMID: 32219428
citation: Zhang B, Liu S, Tan T, Huang W, Dong Y, Chen L, Chen Q, Zhang L, Zhong Q, Zhang X, Zou Y, Zhang S. Treatment With Convalescent Plasma for Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Chest. 2020 Jul;158(1):e9-e13. doi: 10.1016/j.chest.2020.03.039. Epub 2020 Mar 31.
PMID: 32243945
citation: Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, Zhou M, Chen L, Meng S, Hu Y, Peng C, Yuan M, Huang J, Wang Z, Yu J, Gao X, Wang D, Yu X, Li L, Zhang J, Wu X, Li B, Xu Y, Chen W, Peng Y, Hu Y, Lin L, Liu X, Huang S, Zhou Z, Zhang L, Wang Y, Zhang Z, Deng K, Xia Z, Gong Q, Zhang W, Zheng X, Liu Y, Yang H, Zhou D, Yu D, Hou J, Shi Z, Chen S, Chen Z, Zhang X, Yang X. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A. 2020 Apr 28;117(17):9490-9496. doi: 10.1073/pnas.2004168117. Epub 2020 Apr 6.
PMID: 32253318
citation: Ahn JY, Sohn Y, Lee SH, Cho Y, Hyun JH, Baek YJ, Jeong SJ, Kim JH, Ku NS, Yeom JS, Roh J, Ahn MY, Chin BS, Kim YS, Lee H, Yong D, Kim HO, Kim S, Choi JY. Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea. J Korean Med Sci. 2020 Apr 13;35(14):e149. doi: 10.3346/jkms.2020.35.e149.
PMID: 32281317
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: No