Trial NCT04803370
Publication Bargay-Lleonart J, J Clin Med (2022) (published paper)
Primary outcome on the report: Time to recover or achieve clinical improvement, where recovery is defined as the first day on which the subject satisfies one of the following three categories from the ordinal scale: (1) Not hospitalized, no limitations on activities (Point = 8); (2) not hospitalized, limitation on activities, and/or requiring home oxygen (Point = 7); (3) hospitalized, not requiring supplemental oxygen—no longer requires ongoing medical care (Point = 6)

Note: The risk of bias by domain corresponds to the highest risk of bias among outcomes by domain.
The overall risk of bias corresponds to the overall highest risk of bias assessed among outcomes.

Bias Author's judgement Support for judgement
Randomization
Some concerns 		Quote: "A random number computer system (Microsoft Excel® specific matrix for randomization) generated a randomization sequence with a balanced permuted block design (block size 2). Randomization was performed in a proportion of 2:1 (plasma group:control group)."
Comment: Allocation sequence random
No information on allocation concealment
Deviations from intervention
Low 		Quote:"Open-label"
Comment: Unblinded study (participants and personnel/carers)
Deviations from intended intervention arising because of the study context:
Deviations from intended intervention arising because of the study context:
No participant cross-over.
Co-interventions of interest reported and balanced between groups: antivirals and corticosteroids. Anticoagulants, Antibiotics, Corticosteroids, antivirals were reported.
Hence, deviations did not arise because of the trial context.
Our analysis for the binary outcome is an intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention.
Risk assessed to be low for the outcomes: Mortality (D28). Adverse events. Serious adverse events.
Missing outcome data
Low 		Comment: 55 participants randomized; 54 participants analyzed.
Data available for nearly all participants randomized.
Risk assessed to be low for the outcomes: Mortality (D28). Adverse events. Serious adverse events.
Measurement of the outcome
Some concerns 		Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups.
Unblinded study (outcome assessor)

MORTALITY
Observer-reported outcome not involving judgement.
Risk assessed to be low for the outcomes: Mortality (D28).

ADVERSE and SERIOUS ADVERSE EVENTS
The authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected events, which can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic.
Risk assessed to be some concerns for the outcomes: Adverse events. Serious adverse events.
Selection of the reported results
Some concerns 		Comment: The retrospective registry was available (dated March 2021)
No information on whether the result was selected from multiple outcome measurements or analyses of the data.
No information on whether the trial was analyzed as pre-specified.
Risk assessed to be some concerns for the outcomes: Adverse events. Serious adverse events.
Mortality outcome was not pre-specified as the registry is retrospective, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned.
Results were probably not selected from multiple outcome measurements or analyses of the data.
Risk assessed to be low for the outcome: Mortality (D28).
Overall risk of bias
Some concerns