COVID-19, SARS-CoV-2, SARS Virus
Conditions
Keywords
SARS Virus, SARS-CoV-2, COVID-19, Blood Plasma
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
Interventions
OTHERConvalescent 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.
OTHERPlacebo
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.
Sponsors
Hospital Italiano de Buenos Aires
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The pharmacist will be unblinded. The study intervention will be covered with an opaque development in order to ensure blinding of the intervention arm.
Intervention model description
Multicenter randomized (2:1, 222 plasma 111 placebo), double-blind, placebo-controlled clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical status during follow-up at 30th day | 30th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentration of neutralizing antibodies at Day 7th | 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) | Plasma concentration of neutralizing antibodies |
| Post-transfusion adverse reactions | In a 30 days follow up period | Post-transfusion adverse reactions between study groups |
| Clinical status during follow-up at 7th day | 7th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) | 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. |
| Clinical status during follow-up at 14th day | 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) | 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. |
| Time until hospital discharge (days). | Whenever the patient is discharge from the hospital or die without discharge, through study completion, an average of 14 days from admission | Hospital discharge or intrahospital death |
| Time until discharge from ICU (days) | Whenever the patient is discharge from ICU or die in ICU, through study completion, an average of 10 days from admission | ICU discharge or ICU death |
| Plasma concentration of neutralizing antibodies at Day 2nd | 2nd Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) | Plasma concentration of neutralizing antibodies |
| Time until complete functional recovery | Whenever the patient returns to basal functional status until 1 month from discharge | Time until complete functional recovery (according to basal status). |
| Percentage of participants with adverse events / serious adverse events | In a 30 days follow up period | Percentage of participants with adverse events / serious adverse events |
| Percentage of patients with negative SARS-CoV-3 PCR at Day 14th | 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) | Percentage of patients with negative SARS-CoV-3 PCR |
| D Dimer plasma concentration at Day 14th | 14th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) | D Dimer plasma concentration |
| Ferritin plasma concentration at Day 13th | 13th Day since study preparation infusion (Placebo or Convalescent SARS COVID-19 plasma) | Ferritin plasma concentration |
| Time to death | In a 30 days follow up period | Death and time to death |
Countries
Argentina
Outcome results
None listed