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: “Randomization was performed by a central computer system whereby stratification occurred according to the number of patients to be assigned to the two study arms.”
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Some concerns |
Quote: “Masking: Single (investigator)(registry)”
Comment: Partially blinded study (investigator) Deviations from intended intervention arising because of the study context: No participant cross-over. Administration of biologics, antivirals and corticosteroids reported. Use of corticosteroids was not balanced between groups (intervention = 50.0%, SC = 72.7%). This deviation was not balanced and could affect the outcome. Nevertheless, this domain was rated as some concern as it is impossible to distinguish deviation because of trial context and deviation because of intervention effect. 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 outcomes: Mortality (D28). Adverse events. |
| Missing outcome data |
Low |
Comment: 96 participants randomized; 92 participants analyzed.
Data available for nearly all participants randomized. Risk assessed to be low concerns for the outcomes: Mortality (D28). Adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Registered as a single-blind (investigator), but no report of blinding in the article. MORTALITY Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcome: Mortality (D28). ADVERSE EVENTS The authors reported on adverse events that may contain both clinically- and laboratory-detected events, which can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcomes: Adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The trial registry was available. Although not prospectively registered (study start 1 April 2020, registry 14 May 2020), no changes were made subsequently and enrolment was mainly carried out in the second Italian wave of COVID-19 pandemics (September and October 2020).
Mortality outcome was not pre-specified in the registry, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. Risk assessed to be low for the outcome: Mortality (D28). Results not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Adverse event were not included in the registry. No information on whether results were 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: Adverse events. |
| Overall risk of bias |
Some concerns |