Plasma Therapy of COVID-19 in Severely Ill Patients
- Conditions
- SARS-CoV-2 Infection
- Interventions
- Biological: Convalescent Plasma (anti-SARS-CoV-2 plasma)Biological: Non-convalescent Plasma (control plasma)
- Registration Number
- NCT04359810
- Lead Sponsor
- Max O'Donnell
- Brief Summary
This randomized blinded multi-center phase 2 trial will assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma among adults with severe COVID-19. Adults ≥18 years of age may participate. A total of 219 eligible subjects will be randomized in a 2:1 ratio to receive either high-titer anti-SARS-CoV-2 plasma or non-convalescent fresh frozen plasma (control plasma).
- Detailed Description
There are few effective therapies for coronavirus disease 2019 (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Exposure to viruses results in an adaptive immune response that commonly include antibodies with neutralization activity. Plasma from subjects who have recovered from viral infections has been used to both prevent or treat disease. Notable examples of the successful use of convalescent plasma (CP) include influenza, measles, Argentine hemorrhagic fever, Middle East respiratory syndrome (MERS), Ebola and severe acute respiratory syndrome (SARS-CoV). Small clinical trials and observational studies of CP therapy in patients with COVID-19 have suggested a possible clinical benefit.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 223
- Willing and able to provide written informed consent prior to performing study procedures or have a legally authorized representative available to do so.
- Age ≥18 years
- Evidence of SARS-CoV-2 infection by PCR test of naso-/oro-pharyngeal swab or tracheal aspirate sample within 14 days of randomization
- Peripheral capillary oxygen saturation (SpO2) ≤ 94% on room air or requiring supplemental oxygen, non-invasive or invasive mechanical ventilation at screening
- Evidence of infiltrates on chest radiography
- Females of childbearing age and males, must be willing to practice an effective contraceptive method or remain abstinent during the study period.
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Participation in another clinical trial of anti-viral agent(s) for COVID-19
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Receipt of any anti-viral agent(s) with possible activity against SARS-CoV-2 <24 hours prior to study drug administration [1]
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Mechanically ventilated (including veno-venous (VV)-ECMO) ≥ 5 days
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Severe multi-organ failure
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History of prior reactions to transfusion blood products meeting definitive case definition criteria, at least severe severity, and probable or definite imputability per National Healthcare Safety Network (NHSN)/Centers for Disease Control and Prevention (CDC) criteria
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Known Immunoglobulin A (IgA) deficiency
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Females who are pregnant
- Use of remdesivir as treatment for COVID-19 is permitted.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Convalescent Plasma (anti-SARS-CoV-2 plasma) Convalescent Plasma (anti-SARS-CoV-2 plasma) Convalescent plasma (1 unit; \~200-250 mL) collected from a volunteer who recovered from COVID-19 disease Non-convalescent Plasma (control plasma) Non-convalescent Plasma (control plasma) Non-convalescent plasma (1 unit; \~200-250 mL) of standard plasma collected prior to December 2019
- Primary Outcome Measures
Name Time Method Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status Up to 28 days Compare the day 28 severity outcome amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups using a 7-point ordinal scale of clinical status. Seven-point ordinal scale for clinical assessment ranges from
1 and 2: Not hospitalized 3: Hospitalized, not requiring supplemental oxygen 4: Hospitalized, requiring supplemental oxygen 5: Hospitalized, requiring high-flow oxygen therapy or noninvasive mechanical ventilation 6: Hospitalized, requiring IMV, ECMO, or both 7: Dead Higher number means worse outcome
- Secondary Outcome Measures
Name Time Method Proportion of SARS-CoV-2 PCR Positivity Up to 14 days Compare the proportion and duration of SARS-CoV-2 PCR positivity (via RT-PCR) amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups at days 0, 7, and 14.
Levels of SARS-CoV-2 RNA Up to 14 days Compare levels of SARS-CoV-2 RNA amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups at days 0, 7, and 14.
Duration of Need for Supplemental Oxygen Up to 28 days Compare duration of need for supplemental oxygen and/or mechanical ventilation amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.
Duration of Hospitalization Up to 28 days Compare duration of hospitalization amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.
28-day Mortality Up to 28 days Compare up to 28-day mortality amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.
Time-to-clinical Improvement In-hospital Up to 28 days Compare time-to-clinical improvement in-hospital amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups, defined as the time to either an improvement of clinical status or alive discharge from the hospital, whichever comes first.
Host Genetic Differences at Day 0 Day 0 To assess for host genetic differences at Day 0 amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.
Host Transcriptomic Differences at Days 0,7,14 Up to 14 days To assess for host transcriptomic differences at Day 0,7,14 amongst the anti-SARS-CoV-2 convalescent plasma and non-convalescent plasma groups.
Trial Locations
- Locations (4)
Columbia University Irving Medical Center/NYP
🇺🇸New York, New York, United States
Hospital Federal dos Servidores do Estado
🇧🇷Rio De Janeiro, Brazil
Hospital Geral de Nova Iguaçu
🇧🇷Rio De Janeiro, Brazil
Instituto Nacional de Infectologia Evandro Chagas
🇧🇷Rio De Janeiro, Brazil
Columbia University Irving Medical Center/NYP🇺🇸New York, New York, United States