Assessment of Safety and Efficacy of CCP

Study Overview
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Brief Summary
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Currently there are no proven treatments or vaccines for COVID-19 and care of the COVID patients is largely supportive involving treatment of symptoms such as fever with antipyretics, secondary bacterial chest infection with antibiotics and meticulous management of comorbid conditions. Several repurposed and new drugs have been investigated for treatment of COVID-19, however, none have been confirmed to be efficacious. These drugs include the antimalarials (chloroquine and hydroxychloroquine), antivirals such as remdesivir and favipiravir and antiretroviral combination therapies such lopinavir/ritonavir. There is emerging evidence to support the use of COVID convalescent plasma for the treatment of COVID-19. There is need to leverage the blood transfusion services in countries and this is beginning to happen on the continent.

Detailed Description
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Currently there are no proven treatments for COVID-19 and current standard therapy is supportive care with oxygen supplementation and treatment of symptoms. While treatments are being investigated in the Western world, it is likely that these data will take several months to become available and if proven to be efficacious, access in most of the low-income countries will be limited due to the high global demand and exorbitant costs. In this study, the investigators aim to assess the safety and efficacy of use of CCP for treatment of adults with COVID-19 in Uganda. The investigators hypothesise that administration of CCP to patients with positive SARS-CoV-2 RT PCR leads to earlier time to viral clearance compared to the standard of care. Objectives: General objective The overall objective of this project is to assess the safety and efficacy of COVID-19 convalescent plasma in the treatment of COVID-19 in Uganda. Primary objective 1. To determine the efficacy of COVID-19 Convalescent Plasma, as measured by time to RT-PCR negativity of COVID-19 patients treated with COVID-19 Convalescent Plasma. Secondary objectives To assess the safety of COVID-19 Convalescent Plasma in the treatment of COVID-19 patients in Uganda To document the time to symptom decrease of patients with positive SARS-CoV-2 RT PCR treated with CCP compared to those on standard of care To assess the ability of CCP therapy to stop progression to severe/critical forms of disease This study will be a prospective randomized two arm open label clinical trial. Patients with confirmed COVID-19 who meet the study eligibility criteria will be randomized to receive either CCP in addition to standard of care therapy or standard of care therapy alone.

Official Title
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Assessment of Safety and Efficacy of COVID-19 Convalescent Plasma for Treatment of COVID-19 in Adults in Uganda; A Randomised Controlled Trial

Conditions
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Covid19

Intervention / Treatment
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* Biological: COVID Convalescent Plasma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with documented laboratory RT PCR confirmed SAR-CoV-2 infection Patients able to provide informed consent. In the event that the patient cannot provide consent e.g. they are severely sick, the next of kin or legal surrogate decision make Exclusion Criteria: Prior diagnosis of IgA deficiency Inability to return for post discharge follow up

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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 study will be a prospective randomized two arm open label clinical trial. Patients with confirmed COVID-19 who meet the study eligibility criteria will be randomized to receive either CCP in addition to standard of care therapy or standard of care therapy alone.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention arm<br>The participants will receive COVID Convalescent Plasma in addition to the standard of care received by all COVID 19 patients | Biological: COVID Convalescent Plasma<br>* Plasma collected from recovered COVID 19 individuals<br>|
| No Intervention: Control arm<br>The participants under this arm will receive the COVID 19 standard of care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to viral clearance (RT-PCR negativity) | The primary end point will be time to viral clearance (RT-PCR negativity). | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to symptom resolution | time to symptom resolution (resolution of the major COVID-19 symptoms of fever, cough, and shortness of breath, rhinorrhea and fatigue) | 28 days | 
| Time to severe/critical disease | Time to clinical improvement as evidenced by the modified ordinal scale for clinical improvement which has 8 states (not hospitalised and not on Oxygen therapy, hospitalised and on oxygen therapy, hospitalised no oxygen therapy, oxygen therapy by nasal prongs (<5l/min), oxygen therapy by mask, SFM or NRM (>10l/min), intubation and mechanical ventilation, ventilation plus additional organ support, death | 28 days | 
| Number of participants reporting an adverse event as evidenced by clinical manifestations | Safety of convalescent plasma as determined by clinical manifestations eg Skin or mucous membrane manifestations, respiratory compromise, Decrease in systolic blood pressure to <90 mmHg or >30% decrease from baseline or a diastolic drop of >30% from baseline, Tachycardia with an increase in resting heart rate to >130 bpm; or bradycardia <40 bpm that is associated with dizziness, nausea or feeling faint, Any other symptom which the good clinical judgment of the physician warrants halting the infusion (i.e., rapid onset of gastrointestinal symptoms, etc.) | 28 days |