Trial NCT04350593
Publication Kosiborod M, Lancet Diabetes Endo, 2021
Primary outcome on the report: 1) A composite of time to new or worsened respiratory, cardiovascular, or kidney organ dysfunction during the index hospitalisation, or death from any cause at any time during the 30 day treatment period. 2) A hierarchical composite that ranked patients into categories using the severity and timing of events experienced during the 30 day treatment period: death, organ dysfunction during the index hospitalisation, supplemental oxygen requirement for patients hospitalised at day 30 without organ dysfunction, and hospital discharge before day 30.

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: "Individuals who met the eligibility criteria were randomly assigned (1:1) to either dapagliflozin 10 mg once daily or to matching placebo with the use of balanced blocks, and randomisation was stratified by country...Participants and trial personnel were unaware of the treatment assignments"
Comment: Allocation sequence random.
Allocation sequence concealed.
Imbalances in baseline characteristics appear to be compatible with chance
Deviations from intervention
Low 		Quote: “Double-blind. Participants and trial personnel were unaware of the treatment assignments.”
Comment: Blinded study (participants and personnel/carers)
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), Time to death (D28). Clinical improvement (D28). Serious adverse events.
Missing outcome data
Low 		Comment: 1250 participants randomized; 1237 participants analyzed.
Data available for all or nearly all participants randomized.
Risk assessed to be low for the outcomes: Mortality (D28), Time to death (D28). Clinical improvement (D28). Serious 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 (D28).Time to death. Clinical improvement (D28).Serious adverse events.
Selection of the reported results
Low 		Comment: The protocol, statistical analysis plan, registry 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 outcomes: Mortality (D28).Time to death. Clinical improvement (D28).Serious adverse events.
Overall risk of bias
Low