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|
|Quote:"Randomization was performed in a 1:1 ratio using a central, electronic, automated system with permuted blocks of 4"
Comment: Allocation sequence random
Allocation sequence concealed
|Deviations from intervention||
Comment: Unblinded study (participants and personnel/carers)
Deviations from intended intervention arising because of the study context:
No participant cross-over.
No information on administration of co-interventions of interest after baseline: antivirals, biologics and corticosteroids.
Hence, no information on whether deviations arose because of the trial context.
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 some concerns for the outcomes: Mortality (D28). Incidence of viral conversion (D7). Clinical improvement (D28). Serious adverse events.
|Missing outcome data||
|Comment: 70 participants randomized; 65 participants analyzed.
Data not available for all or nearly all participants randomized.
No evidence that the result is not biased.
Reasons: 6 patients withdrew consent post-randomization or because they did not meet eligibility criteria. 1 patient was transfered to the ICU before starting intervention.
Missingness could depend on the true value of the outcome.
Not clear whether missingness depended on the true value of the outcome because the number of participants missing by arm is not reported: the flow diagram is missing from the Accepted Manuscript PDF.
Risk assessed to be high for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Clinical improvement (D28). Serious adverse events.
|Measurement of the outcome||
|Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups.
Unblinded study (outcome assessor)
MORTALITY, VIRAL NEGATIVE CONVERSION
Observer-reported outcome not involving judgement.
Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7).
Clinical improvement (defined as discharge) requires clinical judgement and could be affected by knowledge of intervention receipt, but it not considered likely to in the context of a pandemic.
Risk assessed to be some concerns for the outcomes: Clinical improvement (D28).
SERIOUS ADVERSE EVENTS
The authors reported on serious 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: Serious adverse events.
|Selection of the reported results||
|Comment: The supplementary files and registry were available (dated 2020 October 27).
Outcome pre-specified. Mortality outcome pre-specified as part of the composite primary outcome.
Results were not selected from multiple outcome measurements or analyses of the data.
Trial analyzed as pre-specified for mortality.
Negative conversion, clinical improvement (discharge) and serious adverse event outcomes 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 low for the outcome: Mortality (D28). Risk assessed to be some concerns for the outcomes: Incidence of viral negative conversion (D7). Clinical improvement (D28). Serious adverse events.
|Overall risk of bias||