Convalescent Plasma Trial in COVID -19 Patients

Study Overview
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Brief Summary
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Plasma therapy using convalescent plasma has been shown to be effective in severe acute respiratory syndrome, Ebola virus infection and in H1N1 influenza. More recently there has been a report of the use of convalescent plasma in the treatment of 5 ventilated COVID-19 patients with the suggestion of expedited recovery as the patients improved 1 week after the transfusion. However, this was not a clinical trial and the patients were on other antiviral medication.; therefore, there is a need to undertake such a trial to see if deploying plasma with SARS-CoV-2 neutralizing antibody has utility in managing patients infected with COVID-19 in respiratory distress. The objective of this pilot study is to compare plasma therapy using convalescent plasma with antibody against SARS-CoV-2 to usual supportive therapy in COVID-19 patients with pneumonia and hypoxia, and to determine if the clinical course is improved. The difference between groups will allow an effect size to be determined for a definitive clinical trial.

Detailed Description
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Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has developed into a pandemic with serious global public health and economic sequelae. As of March 30, 2020, over 750,000 cases have been confirmed worldwide leading to over 34,000 deaths (https://coronavirus.jhu.edu/map.html). There is no current vaccine available, but there have been a number of reports of medication such as hydroxychloroquine having antiviral properties with efficacy against SARS-CoV-2. Plasma therapy using convalescent plasma has been shown to be effective in severe acute respiratory syndrome, Ebola virus infection and in H1N1 influenza. More recently there has been a report of the use of convalescent plasma in the treatment of 5 ventilated COVID-19 patients with the suggestion of expedited recovery as the patients improved 1 week after the transfusion. However, this was not a clinical trial and the patients were on other antiviral medication; therefore, there is a need to undertake such a trial to see if deploying plasma with SARS-CoV-2 neutralizing antibody has utility in managing patients infected with COVID-19 in respiratory distress. The objective of this pilot study is to compare plasma therapy using convalescent plasma with antibody against SARS-CoV-2 to usual supportive therapy in COVID-19 patients with pneumonia and hypoxia, and to determine if the clinical course is improved. The difference between groups will allow an effect size to be determined for a definitive clinical trial Could using convalescent plasma transfusion, from recovered COVID19 patients with antibody against COVID-19 be beneficial in treatment of COVID19 patients with hypoxia and pneumonia, in order to avoid or delay the need for invasive ventilation? This is a prospective, interventional and randomized open label trial involving 40 patients with COVID-19 who are in respiratory distress, with the criteria that all require oxygen therapy and have radiological evidence of pneumonia, 20 of whom will receive a single transfusion of convalescent patient plasma plus routine care, compared to 20 COVID-19 patients who will receive routine care alone.

Official Title
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Use of Convalescent Plasma Therapy for COVID-19 Patients With Hypoxia: a Prospective Randomized Trial

Conditions
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SARS-CoV 2, COVID-19

Intervention / Treatment
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* Other: plasma therapy using convalescent plasma with antibody against SARS-CoV-2
* Other: Routine care for COVID-19 patients


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COVID-19 diagnosis Hypoxia, (Oxygen saturation of less than or equal 92% or PO2 < 60mmHg on arterial blood gas analysis) and patient requiring oxygen therapy Evidence of infiltrates on Chest Xray or CT scan Able to give informed consent Patients between the ages of 21 and above with no upper age. Exclusion Criteria: Patients with mild disease not requiring oxygen therapy Patients with normal CXR & CT scan Patients requiring ventilatory support Patients with a history of allergy to plasma, sodium citrate or methylene blue Patients with a history of autoimmune disease or selective IGA deficiency.

Ages Eligible for Study
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Minimum Age: 21 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 prospective, interventional and randomized open label trial involving 40 patients with COVID-19 who are in respiratory distress, with the criteria that all require oxygen therapy and have radiological evidence of pneumonia, 20 of whom will receive a transfusion of convalescent patient plasma plus routine care, compared to 20 COVID-19 patients who will receive routine care alone.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control group<br>local standard of care which include antivirals and supportive care | Other: Routine care for COVID-19 patients<br>* local standard of care which include antivirals and supportive care<br>|
| Experimental: Intervention group<br>convalescent patient plasma 400ml given as 200ml over 2 hours in 2 consecutive days, plus routine local standard of care | Other: plasma therapy using convalescent plasma with antibody against SARS-CoV-2<br>* convalescent patient plasma plus routine local standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Requirement for invasive ventilation | Could the plasma therapy avoid or delay the need for invasive ventilation | through study completion up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in viral clearance | Through the use of CT values | through study completion up to 28 days | 
| Radiological change | Chest Xray | through study completion up to 28 days | 
| Change in white cell count | As a measure of a change in inflammation | through study completion up to 28 days | 
| C reactive protein measurement | A change in C reactive protein as a measure of a change in inflammation | through study completion up to 28 days | 
| lactate dehydrogenase measurement | A change in lactate dehydrogenase as a measure of an improvement in the severity of the disease process | through study completion up to 28 days | 
| Procalcitonin measurement | A change in procalcitonin as a measure of an improvement in the severity of the disease process | through study completion up to 28 days | 
| D Dimer measurement | A change in D Dimer as a measure of an improvement in the severity of the disease process | through study completion up to 28 days | 
| Ferritin measurement | A change in Ferritin as a measure of an improvement in the severity of the disease process | through study completion up to 28 days | 
| Troponin T measurement | A change in troponin T as a measure of an improvement in the severity of the disease process | through study completion up to 28 days | 
| Brain naturetic peptide measurement | A change in brain naturetic peptide as a measure of an improvement in the severity of the disease process | through study completion up to 28 days | 
| Mortality rate | Mortality rate due to COVID-19 | Up to 28 days of the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plasma Therapy, COVID-19