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: "Randomisation was centralized through REDCap Cloud, and patients were randomised in a 1:1:1
allocation ratio to a single infusion of canakinumab 600 mg intravenous (IV), canakinumab 300 mg IV, and
placebo with stratification by hospital and whether or not the patient was intubated at the time of enrollment."
Comment: Allocation sequence random. Allocation sequence probably concealed |
| Deviations from intervention |
Low |
Quote: "double-blind" (report) "Subjects, investigator staff, persons performing the assessments, and the clinical trial team will be blinded to treatment. Only the Research Pharmacist and members of the Data Safety Monitoring Board will have access to the treatment assignments" (protocol)
Comment: Blinded study (participants and personnel/carers). Our analysis for the 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). Mortality (D60 or more). Time to death. Clinical improvement (D28). WHO score 7 and above (D28). Serious adverse events. |
| Missing outcome data |
Low |
Comment: 45 participants randomized; 45 participants analyzed.
Data available for all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Clinical improvement (D28). WHO score 7 and above (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). Mortality (D60 or more). Time to death. Clinical improvement (D28). WHO score 7 and above (D28). Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol (dated May 11th, 2020), statistical analysis plan, registry (earliest version dated April 24th, 2020) were available.
MORTALITY, TIME TO DEATH, WHO SCORE 7 AND ABOVE, SERIOUS ADVERSE EVENTS Outcomes were 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). Mortality (D60 or more). Time to death. WHO score 7 and above (D28). Serious adverse events. CLINICAL IMPROVEMENT Outcome 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: Clinical improvement (D28). |
| Overall risk of bias |
Some concerns |