Convalescent Plasma and Placebo for the Treatment of COVID-19 Severe Pneumonia (PLASM-AR)

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

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.

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

Multicenter randomized (2:1, 222 plasma 111 placebo), double-blind, placebo-controlled clinical trial

The pharmacist will be unblinded. The study intervention will be covered with an opaque development in order to ensure blinding of the intervention arm.

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.

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.

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.

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.

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.

Whenever the patient is discharge from the hospital or die without discharge, through study completion, an average of 14 days from admission

Whenever the patient is discharge from ICU or die in ICU, through study completion, an average of 10 days from admission

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.

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