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: “Randomized treatment was open label. Patients were assigned to a serial number by the study coordinator. Each serial number was linked to a computer-generated randomization list assigning the antiviral treatment regimens. The study medications was dispensed by the hospital pharmacy and then to the patients by the medical ward nurses.”
Comment: Allocation sequence random.
No information on allocation concealment.
|Deviations from intervention||
|Quote: “Open label”
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: biologics (other than the intervention). Antivirals and corticosteroids were reported. Corticosteroid administration was lower in the combined therapy group.
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.
MORTALITY.SERIOUS ADVERSE EVENTS
Our analysis for the binary mortality and serious adverse events outcomes 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). Serious adverse events.
TIME TO CLINICAL IMPROVEMENT. TIME TO VIRAL NEGATIVE CONVERSION
Participants were analyzed according to their randomized groups for the time to viral negative conversion and time to clinical improvement.
Risk assessed to be some concerns for the outcomes: Time to clinical imrpovement. Time to viral negative conversion.
|Missing outcome data||
|Comment: 212 participants randomized; 212 participants analyzed.
Data available for all or nearly all participants randomized.
Risk assessed to be low for the outcomes: Mortality (D28). Time to viral negative conversion. Time to clinical improvement. 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.TIME TO VIRAL NEGATIVE CONVERSION
Mortality and viral negative conversion are observer-reported outcomes not involving judgement.
Risk assessed to be low for the outcomes: Mortality (D28). Time to viral negative conversion.
TIME TO CLINICAL IMPROVEMENT
Clinical improvement (Achieve WHO Clinical Progression Scale (WCPS)=1 maintained for 24 hours i.e., asymptomatic) requires clinical judgement and could be affected by knowledge of intervention receipt, but it is not considered likely to in the context of a pandemic.
Risk assessed to be some concerns for the outcomes: Time to clinical improvement.
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 trial registry was available but was retrospective.
Mortality outcome was not pre-specified, 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).
TIME TO VIRAL NEGATIVE CONVERSION. TIME TO CLINICAL IMPROVEMENT. SERIOUS ADVERSE EVENTS
No information on whether time to negative conversion, time to clinical imrpovement and adverse event results were selected from multiple outcome measurements or analyses of the data.
No information on whether the trial was analyzed as pre-specified.
Risk assessed to be some concerns for the outcomes: Time to viral negative conversion. Iime to clinical improvement. Serious adverse events.
|Overall risk of bias||