Convalescent Plasma as Adjunctive Therapy for Hospitalized Patients With COVID-19

Study Overview
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Brief Summary
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This protocol provides access to investigational convalescent plasma for hospitalized patients with COVID-19. Following provision of informed consent, patients will be administered around 500 mL of convalescent plasma obtained from an individual who has recovered from a documented SARS-CoV-2 infection. The study aims to evaluate the efficacy and safety of anti-SARS-CoV-2 convalescent plasma as adjunctive therapy in preventing disease progression (prevention of ICU admission) among hospitalized patients with COVID-19. Safety outcomes include serious adverse events judged to be related to convalescent plasma. Other information which will be collected includes patient demographics and clinical data which includes quick SOFA scores, ventilator-free days, ICU-free days, dialysis-free days and 28-day mortality.

Detailed Description
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This is a phase 3, randomized, non-placebo controlled, open-label, single-center clinical trial which will assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma given from the 3rd to 14th day of illness after the onset of symptoms in preventing ICU admission among hospitalized COVID-19 patients compared to standard of care. Consecutive patients with COVID-19 admitted to the UP Philippine General Hospital will be offered participation into the study. Patients in the intervention group will receive one dose of type-specific anti-SARS-CoV-2 convalescent plasma (500 mL collected by whole blood donation or standard pheresis at the UP-PGH blood bank from a volunteer who recovered from COVID-19). The primary safety endpoints include serious adverse events judged to be related to convalescent plasma. The study also aims to compare anti-SARS-CoV-2 antibody titers and rates, levels, and duration of SARS-CoV-2 RNA in nasopharyngeal swabs using RT-PCR between the intervention and control groups.

Official Title
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A Randomized, Open-Label, Single Center Clinical Trial to Assess the Efficacy and Safety of Convalescent Plasma to Hospitalized Adult COVID-19 Patients as Adjunctive Therapy to Reduce the Need for ICU Admission: Co-CLARITY Trial

Conditions
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Covid19

Intervention / Treatment
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* Drug: Anti-SARS-CoV-2 convalescent plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must be 19 years of age or older Hospitalized with COVID-19 and confirmed via SARS-CoV-2 RT-PCR testing Patient is willing and able to provide written consent and comply with all protocol requirements Patient agrees to storage of specimens for future testing Exclusion Criteria: Female subjects with positive pregnancy test, are breastfeeding or planning to become pregnant/breastfeed during the study period Symptomatic illness exceeding 14 days from onset of illness at time of enrollment ICU admission on initial presentation at the hospital (includes patients with clinical indications for ICU admission as follows: Respiratory distress with requirement of O2 >6 lpm to maintain O2 sat >92% Rapid escalation of O2 requirement/significant work of breathing Hemodynamic instability: SBP <90, MAP <65 Receipt of any blood products including pooled immunoglobulin or intravenous immunoglobulin (IVIg) in the past 30 days prior to enrolment Known IgA deficiency Presence of any contraindication to transfusion (or history of prior severe reactions to transfusion of blood products)

Ages Eligible for Study
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Minimum Age: 19 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
Interventional Model Description: This is a phase 3, randomized, non-placebo controlled, open-label, non-blinded, single-center clinical trial which will assess the efficacy and safety of anti-SARS-CoV-2 convalescent plasma given from the 3rd to 14th day of illness after the onset of symptoms in preventing ICU admission among COVID-19 patients compared to standard of care. Consequently enrolled patients will be randomized using the REDCap randomization module
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anti-SARS-CoV-2 convalescent plasma<br>About 500 mL of type-specific anti-SARS-CoV-2 convalescent plasma collected by whole blood donation or standard pheresis from a volunteer who recovered from COVID-19 transfused intravenously as 2 aliquots of 250 mL | Drug: Anti-SARS-CoV-2 convalescent plasma<br>* convalescent plasma derived from whole blood donors or standard pheresis from a volunteer who recovered from COVID-19<br>|
| No Intervention: Standard of care<br>Patients in the control group are those will only receive local standard of care as deemed appropriate by the primary attending physicians and guided by institutional pathways | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of serious adverse events | Cumulative incidence of serious adverse events (transfusion-related acute lung injury, transfusion associated circulatory overload, transfusion related infection and anaphylaxis/severe allergic reactions) during the study period | 28 days from enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quick SOFA (qSOFA) score | Quick Sequential Organ Failure Assessment (qSOFA) scores of study participants within 28 days from enrollment. The qSOFA score is a rapid bedside clinical score used to identify patients with suspected infection that are at a greater risk for a poor outcome. Minimum score is 0 and maximum score is 3. A higher score is associated with higher risk for in-hospital mortality. | 28 days from enrollment | 
| Cardiopulmonary arrest | Total number of patients experiencing cardiopulmonary arrest | 28 days from enrollment | 
| ICU mortality | Total number of deaths among patients admitted to the ICU | 28 days from enrollment | 
| ICU length of stay | Total number of days patients were admitted to the ICU | 28 days from enrollment | 
| Hospital mortality | Total number of deaths among study participants | 28 days from enrollment | 
| Hospital length of stay | Total number of days patients were admitted to the hospital | 28 days from enrollment | 
| Dialysis-free days | Days without dialysis within 28 days from enrollment | 28 days from enrollment | 
| Vasopressor-free days | Days without vasopressors within 28 days from enrollment | 28 days from enrollment | 
| ICU-free days | Days without need for ICU admission within 28 days from enrollment | 28 days from enrollment | 
| 28-day mortality | Total number of patient deaths within 28 days from enrollment | 28 days from enrollment | 
| Anti-SARS-CoV-2 antibody titers | Anti-SARS-CoV-2 IgG antibody titers | days 0, 1, 7 and 14 of enrollment | 
| SARS-CoV-2 RNA by RT-PCR | Levels of SARS-CoV-2 RNA in nasopharyngeal swabs (or other specimen types as available) using RT-PCR | days 0, 1, 7 and 14 of enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Convalescent plasma