Convalescent Plasma and Placebo for the Treatment of COVID-19 Severe Pneumonia

Study Overview
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Brief Summary
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A multicenter randomized, double-blind, placebo-controlled clinical trial of Convalescent SARS COVID-19 plasma versus Placebo to evaluate the effect between arms on an ordinal score of six mutually exclusive categories of clinical status at day 30 after study initiation.

Detailed Description
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Introduction The use of convalescent plasma in the treatment of infectious diseases has been empirically performed for more than a century. It is based upon the assumption that providing exogenous neutralizing antibodies may provide protection while affected patients mount their own immune response. This therapeutic approach appears of particular interest in the context of the current pandemic, in which there is no specific vaccine available nor adequately proven effective pharmacological treatments. Study purpose, hypothesis and general design Purpose of the study: evaluate the effectiveness and safety of convalescent plasma in the treatment of SARS-CoV-2 pneumonia (Covid-19) Hypothesis: Convalescent plasma significantly improves the clinical outcome in patients with Covid-19 pneumonia and severity criteria. Multicenter randomized, double-blind, placebo.controlled clinical trial. Placebo will be a saline solution. 3. Methodological sustain for including a control arm with placebo Quality evidence about the effectiveness of convalescent plasma in the treatment of Covid-19 pneumonia is not yet available. Although case series and anecdotal reports appear encouraging, the implementation of its use in routine clinical practice requires the validation through controlled clinical trials. In addition the collection, administration and control of plasma is technically demanding and needs a clear support before broadly recommending it. Different scientific institutions and international organisms had clearly suggested to prioritize the application of novel therapeutic techniques with yet unproven efficacy within the context of clinical studies over its empirical use. On the other hand, for the present study, intervention strategy is proposed in add-on modality over the antiviral treatment that each participant may be already receiving, since they represent completely different therapeutic approaches. As such, participation in the present study will not condition the possibility of the participants to receive other treatments, either in intervention or control arms. 4. Study objectives Primary objective Analyze the difference between arms on an ordinal score of six mutually exclusive categories at day 30 after study initiation. This score includes the following categories

Official Title
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Randomized, Double-blind, Placebo-controlled Clinical Trial of Convalescent Plasma for the Treatment of COVID-19 Pneumonia With Severity Criteria

Conditions
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SARS Virus, SARS-CoV-2, COVID-19

Intervention / Treatment
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* Other: Convalescent SARS COVID-19 plasma
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of Covid-19 through qualitative polymerase-reverse transcriptase (qRT-PCR -GeneDX Co, Ltd o similar). Imagining-diagnosed pneumonia (Rx or CT scan). MSOFA score (Modified SOFA) of 2 or more (modified organic failure assessment) Informed consent. Exclusion Criteria: Pregnant women Women at reproductive age not willing to avoid unprotected sexual intercourse up to Day 30 after study initiation. Women in the breastfeeding period Patients receiving experimental treatments under development within 30 days prior to study initiation. Patients with a previous history of allergic reactions to blood or blood-components transfusion. Diagnosis or clinical suspicion of an alternative microbiological cause for pneumonia besides COVID-19 Use of systemic corticosteroids within 15 days prior to entering the study.

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
Interventional Model Description: Multicenter randomized (2:1, 222 plasma 111 placebo), double-blind, placebo-controlled clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Convalescent SARS COVID-19 plasma<br>Convalescent SARS COVID-19 plasma from a pool of 10 donor plasma, in addition to standard care. | Other: Convalescent SARS COVID-19 plasma<br>* Convalescent SARS COVID-19 plasma from a pool of 10 donor plasma. The calculation of the volume to be transfused will be from 10 to 15 ml / kg adjusting the volume to the body weight of each patient, at a suggested infusion rate of 5 to 10 ml / kg / h with an intravenous infusion pump. The infusion rate will be adjusted according to the clinical stability of the patient according to the treating physician.<br>|
| Placebo Comparator: Placebo<br>Single infusion of saline solution, in addition to standard care. | Other: Placebo<br>* Single infusion of saline solution, in addition to standard care. The calculation of the volume to be transfused will be from 10 to 15 ml / kg adjusting the volume to the body weight of each patient, at a suggested infusion rate of 5 to 10 ml / kg / h with an intravenous infusion pump. The infusion rate will be adjusted according to the clinical stability of the patient according to the treating physician.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical status during follow-up at 30th day | Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities. | 30th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical status during follow-up at 7th day | Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities. | 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) | 
| Clinical status during follow-up at 14th day | Ordinal outcome with six mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) death; (2) in intensive care; (3) hospitalised but requiring supplemental oxygen; (4) hospitalised and not requiring supplemental oxygen; (5) discharged but unable to resume normal activities; or (6) discharged with full resumption of normal activities. | 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) | 
| Time until hospital discharge (days). | Hospital discharge or intrahospital death | Whenever the patient is discharge from the hospital or die without discharge, through study completion, an average of 14 days from admission | 
| Time until discharge from ICU (days) | ICU discharge or ICU death | Whenever the patient is discharge from ICU or die in ICU, through study completion, an average of 10 days from admission | 
| Time to death | Death and time to death | In a 30 days follow up period | 
| Time until complete functional recovery | Time until complete functional recovery (according to basal status). | Whenever the patient returns to basal functional status until 1 month from discharge | 
| Percentage of participants with adverse events / serious adverse events | Percentage of participants with adverse events / serious adverse events | In a 30 days follow up period | 
| Percentage of patients with negative SARS-CoV-3 PCR at Day 14th | Percentage of patients with negative SARS-CoV-3 PCR | 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) | 
| D Dimer plasma concentration at Day 14th | D Dimer plasma concentration | 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) | 
| Ferritin plasma concentration at Day 13th | Ferritin plasma concentration | 13th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) | 
| Plasma concentration of neutralizing antibodies at Day 2nd | Plasma concentration of neutralizing antibodies | 2nd Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) | 
| Plasma concentration of neutralizing antibodies at Day 7th | Plasma concentration of neutralizing antibodies | 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) | 
| Post-transfusion adverse reactions | Post-transfusion adverse reactions between study groups | In a 30 days follow up period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS Virus, SARS-CoV-2, COVID-19, Blood Plasma