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: "This is a randomized, double-blind study...the study site will obtain the
patient's identification number and treatment assignment from an interactive voice or web-based response system (IxRS)."
Comment: Allocation sequence random. Allocation sequence probably concealed. |
| Deviations from intervention |
Some concerns |
Quote: “Double (Participant, Investigator)”
Comment: Blinded study (participants and personnel/carers) MORTALITY. ADVERSE AND SERIOUS ADVERSE EVENTS 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. (TIME TO) VIRAL NEGATIVE CONVERSION Participants were analyzed according to their randomized groups for the outcome. Of note, 4 participants were excluded from the analysis post-randomization because they did not receive any amount of study drug. This method was considered inappropriate to estimate the effect of assignment to intervention for this outcome. There was probably no substantial impact of failure to analyze participants according to their randomized groups. Of note, 1 vs 1 were excluded for unknown reason, this will accounted for in domain 3 as missing data. Risk assessed to be some concerns for the outcomes: Incidence of viral negative conversion (D7). Time to viral negative conversion. |
| Missing outcome data |
Low |
Comment: 104 participants randomized; 100 participants analyzed mortality, AE and SAE, 98 analyzed for viral negative conversion.
Data available for nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Time to viral negative conversion. Adverse events. Serious adverse events. |
| Measurement of the outcome |
Low |
Quote: "Double-Blind, Placebo-Controlled"
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). Incidence of viral negative conversion (D7). Time to viral negative conversion. Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol (first version dated November 23, 2020), statistical analysis plan and registry were available (dated January 13, 2021).
(TIME TO) VIRAL NEGATIVE CONVERSION. ADVERSE AND SERIOUS ADVERSE EVENTS. Outcome pre-specified in the registry/protocol. 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: Incidence of viral negative conversion (D7). Time to viral negative conversion. Adverse events. Serious adverse events. MORTALITY Mortality outcome was not pre-specified in the registrY, 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. Trial analyzed as pre-specified. Risk assessed to be low for the outcome: Mortality (D28). |
| Overall risk of bias |
Some concerns |