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Convalescent Plasma for Severe COVID-19 Patients (PLACOVID)

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ClinicalTrials.gov Identifier: NCT04547660
Recruitment Status : Completed
First Posted : September 14, 2020
Last Update Posted : February 9, 2021
Sponsor:
Collaborators:
Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil
Instituto Cultural Floresta
Information provided by (Responsible Party):
Hospital de Clinicas de Porto Alegre

Tracking Information
First Submitted Date  ICMJE September 9, 2020
First Posted Date  ICMJE September 14, 2020
Last Update Posted Date February 9, 2021
Actual Study Start Date  ICMJE July 16, 2020
Actual Primary Completion Date January 7, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 11, 2020)
Clinical improvement [ Time Frame: 28 days ]
Improvement of 2 points from randomization in a 6-point ordinal severity scale (6 points, death; 5 points, hospitalization plus extracorporeal membrane oxygenation (ECMO) or invasive mechanical ventilation; 4 points, hospitalization plus noninvasive ventilation or high-flow supplemental oxygen; 3 points, hospitalization plus supplemental oxygen (not high-flow or noninvasive ventilation); 2 points, hospitalization with no supplemental oxygen; 1 point, hospital discharge)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2020)
  • 6-point ordinal scale proportion at 14 days [ Time Frame: 14 days from randomization ]
    Proportions of individuals classified in each 6-point ordinal scale strata
  • 6-point ordinal scale proportion at 28 days [ Time Frame: 28 days from randomization ]
    Proportions of individuals classified in each 6-point ordinal scale strata
  • Overall mortality [ Time Frame: 14 days ]
    Death from any cause after randomization
  • Overall mortality [ Time Frame: 28 days ]
    Death from any cause after randomization
  • Days alive and free of respiratory support (DAFOR28) [ Time Frame: 28 days ]
    Days free of respiratory support during follow up
  • Mechanical ventilation [ Time Frame: 28 days ]
    Duration of invasive ventilatory support (for those who received mechanical ventilation)
  • PaO2/FiO2 ratio [ Time Frame: At the 7th day of randomization ]
    PaO2/FiO2 ratio at 7 days of follow up
  • Hospital stay [ Time Frame: 28 days ]
    Time from randomization to hospital discharge (for 28-day survivors)
  • Lactate Dehydrogenase [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    LDH (U/L)
  • Troponin I [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    Troponin I (pg/mL)
  • C Reactive Protein [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    CRP (mg/L)
  • D-Dimers [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    D-Dimers (mcg/mL)
  • Fibrinogen [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    Fibrinogen (mg/dL)
  • Prothrombin Time (PT) [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    PT (seconds)
  • Activated Partial Thromboplastin Time (APTT) [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    APTT (seconds)
  • Tumor Necrosis Factor Alfa (TNF-Alfa) [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    TNF-Alfa (pg/mL)
  • Interleukin-6 (IL-6) [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    IL-6 (pg/mL)
  • RT-PCR [ Time Frame: At the 7th day of randomization (or at hospital discharge if earlier than 7 days) ]
    Nasal and Oropharyngeal Swab RT-PCR
  • Sequential Organ Failure Assessment (SOFA) score [ Time Frame: At the 7th day of randomization ]
    SOFA score at 7 days of randomization (ranges from 0 to 24, prognosis worsens with higher score values)
  • National Early Warning Score 2 (NEWS) 2 [ Time Frame: 7 and 14 days of randomization ]
    Change in NEWS 2 from randomization at 7 days and 14 days (ranges from 0 to 20, prognosis worsens with higher score values)
  • Safety and Adverse Events [ Time Frame: 28 days ]
    CTCAE grade 3-4 events during follow up
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Convalescent Plasma for Severe COVID-19 Patients
Official Title  ICMJE Convalescent Plasma for Severe COVID-19 Patients: a Randomized, Open-label, Phase 3 Trial
Brief Summary Plasma, the supernatant part of blood, contains a variety of different proteins, including immunoglobulins. These proteins, also called antibodies, are directed to previous foreign infecting organisms, such as virus, bacteria or parasites. Patients recovering from SARS-Cov-2 infection may develop protective antibodies which can prevent reinfection with the same agent or similar organisms with shared molecular structures. Those antibodies may be transferred to other patients through collection of such convalescent plasma from recovered donors and its transfusion to ill patients. In this research, the primary hypothesis is that those antibodies can exert passive immunization and help ameliorate symptoms from COVID-19 (Coronavirus Disease 2019), resulting in higher clinical improvement rates at day 28, especially when administered early in the infection course.
Detailed Description This is a randomized, open-label, phase 3 clinical trial on the use of convalescent plasma for severe COVID-19 patients. In this research, we are going to assess efficacy and safety of convalescent plasma in the treatment of severely compromised COVID-19 patients. Convalescent plasma will be collected from recovered COVID-19 patients, who will be recruited as plasma donors and will be submitted to apheresis (with minimum interval of 14 days) to obtain two aliquots of 300 ml of convalescent plasma, which will be frozen at -80 and stored at -20 to -30 degrees Celsius. Enrolled patients will be randomized based on a concealed sequential allocation list by an independent researcher which will not be aware of patients characteristics, and stratified by COVID-19 severity (severe or life-threatening). There will be two arms of study, intervention or control group, and patients will be followed up for the next 28 days for clinical and laboratory outcomes such as improvement of disease status (measured by a 6-point ordinal severity scale); mechanical ventilation, intensive care unit (ICU) and total hospital stay period; cytokine levels (IL-6 and TNF-alfa) and several inflammatory, cellular injury and coagulation parameters. Intervention was conceived as two infusions of 300 ml of convalescent plasma, 2 days apart. Control group will receive full supportive treatment but will not be allowed to receive other investigational drugs. Sample size was calculated to a total of 160 patients, with a 1:1 randomization proportion between groups. This amount would be capable to detect an 18% or higher difference in the proportion of clinical improvement at 28 days of enrollment between intervention and control groups, with an alfa error of 0.05 and a statistical power of 0.8.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized, open-label, phase 3, comparing best supportive care (BSC, no investigational drugs allowed) and convalescent plasma, along BSC.
Masking: Single (Outcomes Assessor)
Masking Description:
Outcomes will be analyzed by blinded investigators. Group allocation will not be disclosed during statistical analysis.
Primary Purpose: Treatment
Condition  ICMJE Covid19
Intervention  ICMJE
  • Biological: Convalescent Plasma
    Fresh frozen plasma collected by apheresis from recovered COVID-19 patients added to best supportive care.
  • Other: Best Supportive Care
    Any form of ventilatory support, extracorporeal membrane oxygenation, steroids, antibiotics and other supportive measures except for investigational interventions.
    Other Name: Standard Treatment
Study Arms  ICMJE
  • Experimental: Convalescent Plasma
    Transfusion of 2 aliquots of 300 ml of frozen convalescent plasma, 2 days apart, thawed at 37 degrees Celsius before infusion. Best supportive care except for investigational interventions.
    Interventions:
    • Biological: Convalescent Plasma
    • Other: Best Supportive Care
  • Active Comparator: Best Supportive Care
    Any form of ventilatory support, extracorporeal membrane oxygenation, steroids, antibiotics and other supportive measures except for investigational interventions.
    Intervention: Other: Best Supportive Care
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 11, 2020)
160
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE January 7, 2021
Actual Primary Completion Date January 7, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Age equal to or greater than 18 yers;
  2. Diagnosis of SARS-CoV-2 infection through nasal cavity or oropharynx swab RT-PCR;
  3. Severe COVID-19 defined by the presence of at least 1 of the following:

    A. Respiratory rate> 30 breaths per minute in room air; B. Oxygen saturation (O2) ≤93% in room air; C. PaO2 / FiO2 ratio ≤300; D. Need for supplemental O2 to maintain O2 saturation> 95%; E. Need for therapy with supplemental O2 by high flow catheter or non-invasive ventilation or invasive mechanical ventilation;

  4. Onset of symptoms in a period not exceeding 14 days.

Exclusion Criteria:

  1. Impossibility for any reason to perform the first plasma infusion within 14 days of the onset of symptoms;
  2. Use of immunosuppressants for other underlying diseases, except corticosteroids for the SARS-CoV-2, in the last 30 days before enrollment;
  3. Pregnancy;
  4. History of serious adverse reactions such as transfusion anaphylaxis;
  5. Participation in another interventional clinical trial;
  6. Disagreement of attending physician;
  7. Disagreement of the patient or legal representative to participate in the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04547660
Other Study ID Numbers  ICMJE 2020-0158
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Hospital de Clinicas de Porto Alegre
Study Sponsor  ICMJE Hospital de Clinicas de Porto Alegre
Collaborators  ICMJE
  • Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil
  • Instituto Cultural Floresta
Investigators  ICMJE
Principal Investigator: Leo Sekine, PhD Hospital de Clínicas de Porto Alegre
Study Director: Alexandre P Zavascki, PhD Federal University of Rio Grande do Sul
PRS Account Hospital de Clinicas de Porto Alegre
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP