Trial NCT04516811
Publication PROTECT-Patient - van den Berg K, Sci Rep (2022) (published paper)
Primary outcome on the report: Successful treatment at Day 28 post-randomization, defined as acute care hospital discharge or clinical improvement of ≥ 2 points on an ordinal scale recommended by the World Health Organization

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: “An electronic randomisation application (REDCap) hosted by SANBS20, was used to generate the treatment allocation.”
Comment: Allocation sequence random. Allocation sequence concealed.
Deviations from intervention
Low 		Quote: “Triple (Participant, Care Provider, Investigator). To mask treatment allocation, investigational product (IP) was covered in opaque paper wrapping prior to dispatch from the blood bank.”
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). Clinical improvement (D28). Adverse events. Serious adverse events.
Missing outcome data
Low 		Comment: 103 participants randomized; 97 participants analyzed.
Data not available for all or nearly all participants randomized.
Evidence that the result is not biased.
Reasons: 5 losses to follow up in the transfusion arm and 1 in the placebo arm for clinical improvement on the ordinal scale (not contactable following discharge or transfer).
The authors report that sensitivity analysis taking losses into account did not alter the study findings.
Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (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). Clinical improvement (D28). Adverse events. Serious adverse events.
Selection of the reported results
Low 		Comment: The prospective registry was available (dated August 18, 2020).
Outcomes pre-specified.
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 (D28). Clinical improvement (D28). Adverse events. Serious adverse events.
Overall risk of bias
Low