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: “Patients were randomized using a web-based system with a 1:1 allocation ratio. Randomization was stratified
by center”
Comment: Allocation sequence probably random and concealed. |
| Deviations from intervention |
Some concerns |
Quote: "the trial was open label"
Comment: Unblinded study. Deviations from intended intervention arising because of the study context: Cross over: 15 (23%) patients in the standard care arm received the study treatment. For 12 (18%) the studied treatment was administered because of clinical worsening as planned in the protocol. Nevertheless, this decision could have been influenced by the trial context. Administration of co-interventions of interest were reported and not balanced: antivirals (35% vs 47%) and corticosteroids (10% vs 10.6%). These deviations 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 outcome: Mortality (D28). Clinical improvement (D28). Time to clinical improvement. Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 126 patients randomized; 123 patients analyzed.
3 participants in the standard care (control) arm withdrew consent on days 2, 3 and 6. Data available for all or nearly all participants. Risk assessed to be low for the outcome: Mortality (D28). Clinical improvement (D28). Time to clinical improvement. Adverse events. Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Unblinded study
Comment: Method of measuring the outcome probably appropriate. Measurement or ascertainment of outcome probably does not differ between groups. Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcome: Mortality (D28). Clinical improvement requires clinical judgement and could be affected by knowledge of intervention receipt. Also, the authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected outcomes. All these outcomes 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: Clinical improvement (D28).Time to clinical improvement. Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The protocol and statistical analysis plan were available.
Results for the outcomes Mortality (D28), Adverse events and Serious adverse events 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). Adverse events. Serious adverse events The outcomes Clinical improvement (defined as discharge) and time to clinical improvement are not present in the protocol or registry. No information on whether the results for these outcomes were selected from multiple outcome measurements or analyses of the data. Risk assessed to be some concerns for the outcomes: Clinical improvement. Time to clinical improvement. |
| Overall risk of bias |
Some concerns |