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 independent statistician prepared an electronically generated randomization list with 14 blocks of 30 participants per block, generated via R software version 3.6.1 (Blockrand package). The list was accessible only to non-blinded pharmacists in the study. Participants were randomized by the study pharmacist to their designated treatment regimen at the time of inclusion and were subsequently identified throughout the study only by their allocated study number".
Comment: Allocation sequence random. Allocation sequence concealed . Any imbalance in the baseline characteristics appears to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: "double-blind, placebo-controlled"
Comment: Blinded study (participants and personnel/carers). Data for the binary 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). Participants were analyzed according to their randomized groups for the time to death outcome. Of note, 15 vs 8 participants were excluded from the analysis post-randomization for reasons unrelated to missing data, before starting treatment. This method was considered inappropriate to estimate the effect of assignment to intervention for this time-to-event outcome. There was probably no substantial impact of failure to analyze participants according to their randomized groups. Risk assessed to be some concerns for the outcome: Time to death. Participants were analyzed according to their randomized groups for the viral negative conversion outcome. Of note, several participants were excluded from the analysis post-randomization for unclear reasons. This method was considered to be probably 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. Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion (D7). |
| Missing outcome data |
High |
Comment: 416 participants randomized, 416 participants analyzed for mortality.
Data available for all participants randomized. Risk assessed to be low for the outcome: Mortality (D28). Comment: 416 participants randomized, 393 participants analyzed for time to death. Data not available for all or nearly participants randomized. No evidence that the result is not biased. Reasons for missing data: excluded before treatment (14 vs 5) which is not due to missing data and is accounted for in domain 2; excluded after treatment (1 vs 3) due to consent withdrawal which is not related to the true value of the outcome. Risk assessed to be low for the outcome: Time to death. Comment: 416 participants randomized, 212 participants analyzed for viral negative conversion. Data not available for all or nearly participants randomized. No evidence that the result is not biased. Reasons for missing data: unknown; at baseline 161 vs 157 were PCR+, denominator at day 7 is 117 vs 95. No information on whether missingness could or is likely to depend on the true value of the outcome. Risk assessed to be high 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 outcome: Mortality (D28). Time to death. Incidence of viral negative conversion (D7). |
| Selection of the reported results |
Some concerns |
Comment: Protocol, trial registry and statistical plan were available.
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). Incidence of viral negative conversion (D7). Time to death is not pre-specified. 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 death. |
| Overall risk of bias |
High |