Clinical trial NCT04383535: Convalescent Plasma and Placebo for the Treatment of COVID-19 Severe Pneumonia
Official title: Randomized, Double-blind, Placebo-controlled Clinical Trial of Convalescent Plasma for the Treatment of COVID-19 Pneumonia With Severity Criteria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: SARS Virus
SARS-CoV-2
COVID-19
Keywords: SARS Virus
SARS-CoV-2
COVID-19
Blood Plasma
Lead sponsor: Hospital Italiano de Buenos Aires
Sponsor class: OTHER
First posted: 2020-05-12
Enrollment: 333
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter randomized (2:1, 222 plasma 111 placebo), double-blind, placebo-controlled clinical trial
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical status during follow-up at 30th day
timeFrame: 30th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
Secondary outcomes:
measure: Clinical status during follow-up at 7th day
timeFrame: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
measure: Clinical status during follow-up at 14th day
timeFrame: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
measure: Time until hospital discharge (days).
timeFrame: Whenever the patient is discharge from the hospital or die without discharge, through study completion, an average of 14 days from admission
measure: Time until discharge from ICU (days)
timeFrame: Whenever the patient is discharge from ICU or die in ICU, through study completion, an average of 10 days from admission
measure: Time to death
timeFrame: In a 30 days follow up period
measure: Time until complete functional recovery
timeFrame: Whenever the patient returns to basal functional status until 1 month from discharge
measure: Percentage of participants with adverse events / serious adverse events
timeFrame: In a 30 days follow up period
measure: Percentage of patients with negative SARS-CoV-3 PCR at Day 14th
timeFrame: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
measure: D Dimer plasma concentration at Day 14th
timeFrame: 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
measure: Ferritin plasma concentration at Day 13th
timeFrame: 13th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
measure: Plasma concentration of neutralizing antibodies at Day 2nd
timeFrame: 2nd Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
measure: Plasma concentration of neutralizing antibodies at Day 7th
timeFrame: 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma)
measure: Post-transfusion adverse reactions
timeFrame: In a 30 days follow up period
Other outcomes:
Locations:
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Hospital Italiano de Buenos Aires
state: Ciudad Autonoma De Buenos Aires
Study officials:
affiliation: Hospital Privado de la Comunidad de Mar del Plata
name: Nora A Fuentes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Italiano de la Plata
name: Florencia Otermin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sanatorio Britanico Rosario, pcia Santa Fe
name: Esteban Nannini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Suiza Argentina
name: Karina Rainiero, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinica Zabala
name: Erica Miyazaki, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sanatorio Agote
name: Gabriela Vidiella, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Austral University, Argentina
name: Wanda Cornistein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Italiano de Buenos Aires
name: Leandro Burgos, MD
role: PRINCIPAL_INVESTIGATOR
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