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: “All patients were randomly assigned to each arm of the study via permuted block randomization (each block-sized for three or six patients) in order to minimize allocation bias in each studied group. The sequence of the randomization was generated via “randomizeR” package using R project for statistics computing version 3.6.1. All randomization codes for individuals enrolled to the study, were sealed in unrecognizable opaque envelopes by the responsible statistician for randomization”
Comment: Allocation sequence random. Allocation sequence concealed |
| Deviations from intervention |
Some concerns |
Quote: “Open-label”
Comment: Unblinded study (participants and personnel/carers). No participant cross-over. No information on administration of co-interventions of interest: antivirals, corticosteroids, biologics. Hence, no information on whether deviations arose because of the trial context. 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). Time to clinical improvement. |
| Missing outcome data |
Low |
Comment: 168 patients randomized; 168 patients analyzed.
Data available for all or nearly all participants. Risk assessed to be low for the outcomes: Mortality (D28). Time to clinical improvement. |
| 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. Unblinded study (outcome assessor) MORTALITY Mortality is an observer-reported outcome not involving judgement, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment. Risk assessed to be low for the outcome: Mortality (D28). TIME TO CLINICAL IMPROVEMENT Clinical improvement (defined as discharge or decline of two steps on the seven-step ordinal scale) requires clinical judgement and 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: Time to clinical improvement. |
| Selection of the reported results |
Some concerns |
Comment: The protocol, published protocol summary and prospective registry were available.
Some outcomes reported and the time points for outcomes differ between the published article and the registry and protocol. 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 outcomes: Mortality (D28). Time to clinical improvement. |
| Overall risk of bias |
Some concerns |