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: "The randomization schedule was prepared by a masked statistician and provided to site-level pharmacists." (publication) "We will use a centralized random allocation schedule, generated by computer and implemented using an online remote access system." (trial registry)
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: "Patients, investigators, health care practitioners, and sponsors were masked to the study drug assignment"
Comment: 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 (D60 or more). Incidence of viral negative conversion (D7). Time to clinical improvement. Adverse events. Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 685 participants randomized; 685 participants analyzed for mortality and time to clinical improvement; 581 participants analyzed for viral negative conversion; 659 participants analyzed for safety.
MORTALITY, CLINICAL IMPROVEMENT AND SAFETY Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D60 or more). Time to clinical improvement. Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons for missing data were not reported. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome (proportions of missing data between arms were similar: 29 (14%) vs 43 (18%) vs 32 (14%)). Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion (D7). |
| 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 (D60 or more). Incidence of viral negative conversion (D7). Time to clinical improvement. Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The prospective versions of the protocol and statistical analysis plan (dated May 19th, 2020) and the registry (dated May 23rd, 2020) were available.
MORTALITY, VIRAL NEGATIVE CONVERSION, AE, SAE 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 (D60 or more). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events. TIME TO CLINICAL IMPROVEMENT Outcome not pre-specified (including the same definition as reported in the paper). No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Time to clinical improvement. |
| Overall risk of bias |
Some concerns |