|Bias||Author's judgement||Support for judgement|
|Quote: "Patients were registered, after giving informed consent to participate, in a web-based eCRF (ORACLE clinical), their baseline clinical data collected and then randomly assigned 1:1 to the investigational treatment, stratified by study site" Comment: No information on allocation concealment|
|Deviations from intervention||
|Comment: Unblinded study.
1 patient did not receive the intervention due to absence of AB0 blood group compatible plasma, therefore not due to the trial context.
Receipt of co-interventions of interest (antivirals, corticosteroids and biologics) were balanced between the two arms.
Outcome data were analyzed by using intention-to-treat analysis.
|Missing outcome data||
|Comment: 81 randomized/81 analyzed for all outomes.
The flow chart of the study shows 4 patients who did not reach end of study (day 29) at the time of database freeze for final analysis (1 experimental arm, 3 control arm), plus 1 patient lost for day 29 follow-up due to consent withdrawal at discharge (control arm)
Missingness unrelated to the true value
Risk assessed to be low for outcomes: Mortality. Time to clinical improvement. WHO score 6 and above. WHO score 7 and above. Serious adverse events.
|Measurement of the outcome||
|Comment: Appropriate method of outcome measurement.
Measurement of outcome does not differ between groups.
Mortality is an observer-reported outcome not involving judgement. For the outcome WHO score 7 and above, we consider that the assessment cannot possibly be influenced by knowledge of the intervention assignment.
Risk assessed to be low for outcomes: Mortality. WHO score 7 and above.
Clinical improvement (defined as improvement of one category on the ordinal scale) and WHO score 6 and above reflects decisions made by the intervention provider. Furthermore, serious adverse events reported contain both clinically- and laboratory-detected events. Assessment of these outcomes could possibly be influenced by knowledge of the intervention assignment but we did not consider this likely to have happened in the context of a pandemic.
Risk assessed to be some concerns for the outcomes: Time to clinical improvement. WHO score 6 and above. Serious adverse events
|Selection of the reported results||
|Comment: Neither the protocol nor the statistical analysis plan was available. Though the authors stated the protocol was included as supplementary material, it could not be found. The registry was available and utilized.
All outcomes, except time to clinical improvement, are listed in the registry and reported in the paper as such.
Results were not selected from multiple outcome measurements or analyses of the data.
Trial analyzed as pre-specified.
Risk assessed to be low for the outcomes: Mortality. WHO score 6 and above. WHO score 7 and above. Serious adverse events.
Time to clinical improvement was not an outcome specified in the registry but was reported in the paper.
No information on whether the results were selected from multiple outcome measurements or analyses of the data.
Risk assessed to be some concerns for the outcome: Time to clinical improvement.
|Overall risk of bias||