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 |
Some concerns |
Quote: (protocol) "Following consent, those subjects meeting all entry criteria will be randomized in a 1:1 ratio. Randomization will be stratified by age (>=50 and <50 years old) and sex."
Comment: Allocation sequence probably random. No information on allocation concealment. |
| Deviations from intervention |
Low |
Quote: “double blinded”
Comment: Blinded study (participants and personnel/carers) MORTALITY. 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). Serious adverse events. TIME TO NEGATIVE CONVERSION Participants were analyzed according to their randomized groups for the outcome. Of note, 3 vs 0 participants were excluded from the analysis post-randomization for unclear reasons, which will be taken into account in domain 3 as missing data. Nevertheless, we considered the analysis to be probably appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Time to negative conversion. |
| Missing outcome data |
Some concerns |
Comment: 49 participants randomized; 49 participants analyzed for mortality and SAE; 46 analyzed for time to negative conversion.
MORTALITY. SERIOUS ADVERSE EVENTS Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Serious adverse events. TIME TO VIRAL NEGATIVE CONVERSION Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: Unclear (probably participants did not have nasal swab data. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome. Risk assessed to be some concerns for the outcome: Time to viral negative conversion. |
| 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). Time to viral negative conversion. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective protocol and statistical analysis plan were available (dated December 4th, 2020). The trial registry was prospective and consulted up to version dated November 14th, 2020.
MORTALITY. SERIOUS ADVERSE EVENTS Outcome pre-specified in the 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 outcome: Mortality (D28). Serious adverse events. TIME TO VIRAL NEGATIVE CONVERSION Outcome pre-specified in the registry. 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 outcome: Time to viral negative conversion. |
| Overall risk of bias |
Some concerns |