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
Other: Convalescent SARS COVID-19 plasma
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.
Other: Placebo
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.
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.
Hospital Italiano de Buenos Aires
Ciudad Autonoma de Buenos Aire, Ciudad Autonoma De Buenos Aires, Argentina