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 from the protocol: "An electronically generated randomization list was prepared by an independent
statistician, with 110 blocks of 4 participants per block. This randomization list was
generated on R software (Package ‘blockrand’). The list will be accessible only to nonblinded
pharmacists in the study, in an attempt to minimize observation bias. Participants will
be randomized by the study pharmacist to their designated treatment regimen at the time of
inclusion and will be subsequently identified throughout the study only by their allocated
study number, always assigned following chronological order." Quote from the pre-print: "An electronically generated randomization list was prepared by an independent statistician, with four blocks of 110 participants per block. This randomization list associated each patient's study number with an opaque surface hiding the treatment group designation. The list was accessible only to non-blinded pharmacists in the study, in an attempt to minimize observation bias. 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, always assigned following chronological order. Unmasking was available to DSMB members in case of severe adverse events." |
| Deviations from intervention |
Low |
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 some concerns for the outcome: Mortality (D28). |
| Missing outcome data |
Low |
Comment: 81 participants randomized, 81 participants analyzed (see Table 2).
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcome: Mortality (D28). |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Comment: Unblinded study (outcome assessor) Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcome: Mortality (D28). |
| Selection of the reported results |
Low |
Comment: The prospective protocol (dated 23rd March, 2020) and registry (dated March 25th, 2020) were available.
Outcome 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 outcome: Mortality (D28). |
| Overall risk of bias |
Low |