Trial NCT04373460
Publication Sullivan D, N Engl J Med (2022) (published paper)
Primary outcome on the report: Covid-19–related hospitalization within 28 days after transfusion, assessed as the cumulative incidence in the convalescent- plasma group as compared with the control-plasma group. Although death before hospitalization was part of the protocol-specified primary outcome, it did not occur in the trial. Hence, the primary outcome is equivalent to Covid-19–related hospitalization.

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
Low 		Quote: "Participants from all sites were randomized by a central web-based system.."
Comment: Allocation sequence random. Allocation sequence concealed.
Imbalances in baseline characteristics appear to be compatible with chance.
Deviations from intervention
Low 		Quote: “Double-blind”
Comment: Blinded study (participants and personnel/carers)
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). Mortality (D60 or more). WHO score 7 and above (D28). or death. Adverse events. Serious adverse events.
Missing outcome data
Low 		Comment: 1225 participants randomized; 1181 participants analyzed.
Of note, 26 vs 18 participants did not receive allocated intervention.
Quote from contact with authors: no missing outcome data for hospitalization. We did have missed day 90 visits outside of primary endpoint""
Data available for all or nearly all participants randomized.
Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Hospitalization or death. WHO score 7 and above (D28). Adverse events. Serious adverse events.
Measurement of the outcome
Low 		Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups.
Blinded study (outcome assessor).
Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Hospitalization or death. WHO score 7 and above (D28). Adverse events. Serious adverse events.
Selection of the reported results
Low 		Comment: The prospective registry (dated April 30 2020) and protocol and SAP (dated May 18 2020) were available

MORTALITY D28, ADVERSE EVENTS, HOSPITALIZATION OR DEATH, WHO SCORE 7 AND ABOVE
Outcomes pre-specified as elements of composite outcomes.
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: Hospitalization or death. WHO score 7 and above (D28). Mortality (D28). Adverse events. Serious adverse events.

MORTALITY D60, SERIOUS ADVERSE EVENTS
Outcome data acquired from contact with authors.
Results were probably not selected from multiple outcome measurements or analyses of the data.
Trial analyzed as pre-specified.
Risk assessed to be low for the outcome: Mortality (D60 or more). Serious adverse events.
Overall risk of bias
Low