Convalescent Plasma in Outpatients With COVID-19

Study Overview
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Brief Summary
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The overarching goal of this project is to confirm or refute the role of passive immunization as a safe and efficacious therapy in preventing the progression from mild to severe/critical COVID-19 illness and to understand the immunologic kinetics of anti-SARS-CoV-2 antibodies after passive immunization.The primary objective is to determine the efficacy and safety of a single dose of convalescent plasma (CP) for preventing the progression from mild to severe COVID-19 illness. The secondary objective is to characterize the immunologic response to CP administration. This study will enroll adults presenting to the emergency department (ED) with mild, symptomatic, laboratory-confirmed COVID-19 illness, who are at high risk for progression to severe/critical illness, but who are clinically stable for outpatient management at randomization.

Official Title
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Clinical-trial of COVID-19 Convalescent Plasma in Outpatients

Conditions
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Covid19

Intervention / Treatment
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* Biological: Convalescent Plasma
* Biological: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: One or more symptoms of COVID-19 illness and laboratory-confirmed SARS-CoV-2 infection Has at least one study defined risk factor for severe COVID-19 illness Clinical team deems stable for outpatient management without supplemental oxygen CP available at the site at the time of enrollment Duration of symptoms ≤ 7 days at ED presentation Informed consent from subject Exclusion Criteria: Age less than 18 years Prisoner or ward of the state Presumed unable to complete follow-up assessments Prior adverse reaction(s) from blood product transfusion Receipt of any blood product within the past 120 days Treating clinical team unwilling to administer 300 ml fluid Enrollment in another interventional trial for COVID-19 illness

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Convalescent Plasma<br>Participants receive 1 unit of convalescent plasma. | Biological: Convalescent Plasma<br>* SARS-CoV-2 convalescent plasma with neutralizing SARS-CoV2 antibodies titers of ≥1:160 administered via intravenous (IV) infusion.<br>|
| Placebo Comparator: Placebo<br>Participants receive 1 unit of saline with multivitamin. | Biological: Saline<br>* Saline with multivitamin administered via intravenous (IV) infusion..<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Disease Progression (Intention-to-treat Population) | Disease progression defined as death or hospital admission or seeking emergency or urgent care within 15 days of randomization. | 15 days | 
| Number of Patients With Disease Progression (Per-protocol Population) | Disease progression defined as death or hospital admission or seeking emergency or urgent care within 15 days of randomization. | 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Worst Severity Rating on the WHO COVID Ordinal Scale for Clinical Improvement During the 30 Days Following Randomization | This scale was developed by a special World Health Organization (WHO) committee for quantifying COVID-19 illness severity. 1 = Not hospitalized without limitation in activity (no symptoms) 2 = Not hospitalized with limitation in activity (continued symptoms) 3 = Hospitalized not on supplemental oxygen 4 = Hospitalized on supplemental oxygen by mask or nasal prongs 5 = Hospitalized on non-invasive ventilation or high flow nasal cannula 6 = Hospitalized, intubated and mechanically ventilated 7 = Hospitalized, intubated, mechanically ventilated and requiring additional organ support (pressors, renal replacement therapy) 8 = Death | 30 days | 
| Number of Patients With Worsening of Symptoms at Day 15 as a Measure of Time to Disease Progression | Assessed on the COVID Outpatient Ordinal Outcome Scale censored at 15 days after randomization. Scale provides more granular detail for outpatients than the WHO scale (adapted from Harrell and Lindsell, 2020). Worsening of symptoms is defined as any subject admitted to the hospital (level 1), seen in the emergency room (level 2), a patient who reports increased symptoms of 2 levels on the scale over a 24 hour period, or a patient who reports increased symptoms of 1 level observed for a 48 hour period. COVID Outpatient Ordinal Outcomes Scale 1 = patient requires care in the hospital 2 = patient requires care in the emergency department or urgent care 3 = patient at home with symptoms rated as moderate (defined as fever, shortness of breath, abdominal pain) 4 = patient at home with symptoms rated as mild (defined as afebrile, constitutional symptoms (flu-like illness) without shortness 5 = patient in their usual state of health | 15 days | 
| Number of Hospital-free Days During the 30 Days Following Randomization |  | 30 days | 
| All-cause Mortality |  | Assessed at 30 days |