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: “Computer-generated randomization lists were used, with permutation blocks of varying sizes elaborated by an independent statistician. The randomization lists were implemented in the electronic case report form to ensure appropriate allocation concealment.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “The DXM intervention, placebo (normal saline) or dexamethasone phosphate (p-DXM), was administered intravenously. The blinding was maintained throughout the study. All analyses were conducted blinded to treatment assignment.”
Comment: Blinded study (participants and personnel/carers). MORTALITY. 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 (D60 or more). Adverse events. TIME TO DEATH Participants were analyzed according to their randomized groups for the outcome. Of note, 37/276 participants in the low-dose arm were randomized prior to a protocol amendment and did not receive low-dose dexamethasone as a trial intervention because the pre-amendment comparison was high-dose dexamethasone versus placebo. Nevertheless, we considered the analysis to be probably appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcome: Time to death. |
| Missing outcome data |
Low |
Comment: 550 participants randomized; 546 participants analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D60 or more). Time to death. Adverse events. |
| 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). Time to death. Adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan and prospective registry were available.
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). Time to death. Adverse events. |
| Overall risk of bias |
Some concerns |