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: "Subjects enrolled in the study will be randomized to receive study drug vs. control using a web-based randomization platform that will pre-generate all treatment assignments in a 2:1 ratio using random permuted blocks of random block sizes. The assignment list is maintained by designated staff at the DCC, independent from the study, and then sent to the Principal Investigator/research team for each participant that is deemed eligible" Comments: Allocation sequence random. Allocation sequence concealed. |
Deviations from intervention |
Low |
Report: "The clinical teams directly managing patients and the trial
clinicians who adjudicated clinical status and determined 28-day outcomes were blinded to
treatment allocation. The hospital blood bank at each site and the clinical research teams who
completed case record forms and performed other study specific procedures were not blinded;
this was done to prevent errors in treatment allocation."
Registry: "Double (Participant, Outcomes Assessor)" Comment: Probably blinded study (participants and personnel/carers) Data for the outcome were analyzed using 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). Time to clinical improvement. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
Missing outcome data |
Low |
Comment: 223 participants randomized; 219 participants analyzed.
Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Time to clinical improvement. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
Measurement of the outcome |
Low |
Quote: "The clinical teams directly managing patients and the trial clinicians who adjudicated clinical status and determined 28-day outcomes were blinded to treatment allocation."
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). Time to clinical improvement. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, and study registry were available.
Outcomes were presented as pre-specified in the May 8th version of the protocol and in the April 21st and 24th, 2020 versions of the registry which was considered to be before unblinded data were available for analysis. WHO score 7 and above had not been pre-specified in these documents at this point. Quote: "The initial primary outcome was time-to-clinical-improvement. However, it became clear that this primary outcome would not reflect instances when patients’ clinical status subsequently worsened after improvement. Thus, the primary outcome of the study was amended to clinical status at day 28, and time-to-clinical-improvement became a secondary outcome. This change was made on August 8th, 2020 (at which point 31% [70/223] of the trial population was enrolled) without any knowledge of outcome data, and the protocol was updated accordingly with approval of the data safety and monitoring board" Hence, specification of this outcome was also considered to be before unblinded data were available for analysis. 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). Time to clinical improvement. WHO score 7 and above (D28). Adverse events. Serious adverse events. |
Overall risk of bias |
Low |