Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Convalescent Plasma for Severe COVID-19 Patients (PLACOVID)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

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.

Condition or disease Intervention/treatment Phase
Covid19 Biological: Convalescent Plasma Other: Best Supportive Care Phase 3

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 160 participants
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
Official Title: Convalescent Plasma for Severe COVID-19 Patients: a Randomized, Open-label, Phase 3 Trial
Actual Study Start Date : July 16, 2020
Actual Primary Completion Date : January 7, 2021
Actual Study Completion Date : January 7, 2021

Arm Intervention/treatment
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.
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

Active Comparator: Best Supportive Care
Any form of ventilatory support, extracorporeal membrane oxygenation, steroids, antibiotics and other supportive measures except for investigational interventions.
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




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Overall mortality [ Time Frame: 14 days ]
    Death from any cause after randomization

  4. Overall mortality [ Time Frame: 28 days ]
    Death from any cause after randomization

  5. Days alive and free of respiratory support (DAFOR28) [ Time Frame: 28 days ]
    Days free of respiratory support during follow up

  6. Mechanical ventilation [ Time Frame: 28 days ]
    Duration of invasive ventilatory support (for those who received mechanical ventilation)

  7. PaO2/FiO2 ratio [ Time Frame: At the 7th day of randomization ]
    PaO2/FiO2 ratio at 7 days of follow up

  8. Hospital stay [ Time Frame: 28 days ]
    Time from randomization to hospital discharge (for 28-day survivors)

  9. Lactate Dehydrogenase [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    LDH (U/L)

  10. Troponin I [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    Troponin I (pg/mL)

  11. C Reactive Protein [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    CRP (mg/L)

  12. D-Dimers [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    D-Dimers (mcg/mL)

  13. Fibrinogen [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    Fibrinogen (mg/dL)

  14. Prothrombin Time (PT) [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    PT (seconds)

  15. Activated Partial Thromboplastin Time (APTT) [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    APTT (seconds)

  16. Tumor Necrosis Factor Alfa (TNF-Alfa) [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    TNF-Alfa (pg/mL)

  17. Interleukin-6 (IL-6) [ Time Frame: Randomization day, Day 3, Day 7 and Day 14 ]
    IL-6 (pg/mL)

  18. 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

  19. 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)

  20. 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)

  21. Safety and Adverse Events [ Time Frame: 28 days ]
    CTCAE grade 3-4 events during follow up



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04547660


Locations
Layout table for location information
Brazil
Hospital de Clínicas de Porto Alegre
Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
Sponsors and Collaborators
Hospital de Clinicas de Porto Alegre
Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil
Instituto Cultural Floresta
Investigators
Layout table for investigator information
Principal Investigator: Leo Sekine, PhD Hospital de Clínicas de Porto Alegre
Study Director: Alexandre P Zavascki, PhD Federal University of Rio Grande do Sul
Publications:

Layout table for additonal information
Responsible Party: Hospital de Clinicas de Porto Alegre
ClinicalTrials.gov Identifier: NCT04547660    
Other Study ID Numbers: 2020-0158
First Posted: September 14, 2020    Key Record Dates
Last Update Posted: February 9, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases