Clinical trial NCT04359810: Plasma Therapy of COVID-19 in Severely Ill Patients
Official title: A Phase 2, Multi-Center, Randomized Clinical Trial to Evaluate the Efficacy and Safety of Human Anti-SARS-CoV-2 Convalescent Plasma in Severely Ill Adults With COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: SARS-CoV-2 Infection
Keywords: COVID-19
COVID
Coronavirus
Convalescent plasma
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: New York Blood Center
name: Amazon, Inc.
First posted: 2020-04-24
Enrollment: 223
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A total of 219 eligible subjects will be randomized in a 2:1 ratio to receive either convalescent plasma qualitatively positive for SARS-CoV-2 antibody (anti-SARS-CoV-2 plasma) or non-convalescent fresh frozen plasma (control plasma).
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* Participation in another clinical trial of anti-viral agent(s) for COVID-19
* Receipt of any anti-viral agent(s) with possible activity against SARS-CoV-2 \<24 hours prior to study drug administration \[1\]
* Mechanically ventilated (including veno-venous (VV)-ECMO) ≥ 5 days
* Severe multi-organ failure
* 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
* Known Immunoglobulin A (IgA) deficiency
* Females who are pregnant

  1. Use of remdesivir as treatment for COVID-19 is permitted.

Primary outcomes:
measure: Number of Participants With Day 28 Severity Outcomes Using a 7-point Ordinal Scale of Clinical Status
timeFrame: Up to 28 days
Secondary outcomes:
measure: Proportion of SARS-CoV-2 PCR Positivity
timeFrame: Up to 14 days
measure: Levels of SARS-CoV-2 RNA
timeFrame: Up to 14 days
measure: Duration of Need for Supplemental Oxygen
timeFrame: Up to 28 days
measure: Duration of Hospitalization
timeFrame: Up to 28 days
measure: 28-day Mortality
timeFrame: Up to 28 days
measure: Time-to-clinical Improvement In-hospital
timeFrame: Up to 28 days
measure: Host Genetic Differences at Day 0
timeFrame: Day 0
measure: Host Transcriptomic Differences at Days 0,7,14
timeFrame: Up to 14 days
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Irving Medical Center/NYP
state: New York
city: Rio De Janeiro
country: Brazil
facility: Hospital Federal dos Servidores do Estado
city: Rio De Janeiro
country: Brazil
facility: Hospital Geral de Nova Iguaçu
city: Rio De Janeiro
country: Brazil
facility: Instituto Nacional de Infectologia Evandro Chagas
Study officials:
affiliation: Columbia University
name: Max O'Donnell, MD
role: PRINCIPAL_INVESTIGATOR
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