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: “Participants who meet all the inclusion criteria and none of the exclusion criteria are randomly
assigned 1:1 to one of the trial arms, using a secure on-line system. The randomisation list has
balanced blocks of fixed size and is stratified by study region.”
Comment: Allocation sequence random Allocation sequence concealed |
Deviations from intervention |
Low |
Quote: “Open label. The allocated treatment is not masked from participants or investigators.”
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. In the outpatient setting, we consider no important cointerventions of interest. Hence, no deviation 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 low for the outcomes: Hospitalization or death. Mortality (D28). Incidence of viral negative conversion (D7). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
Missing outcome data |
Some concerns |
Comment: 217 participants randomized; 215 participants analyzed for WHO score 7 or above, 204 participants analyzed for hospitalization or death, mortality, 107 participants analyzed for viral negative conversion, 201 analyzed for adverse events, 217 participants analyzed for serious adverse events (according to data from authors)
Of note, participants were lost to follow up (4 vs 1) and discontinued intervention (10 vs 14). HOSPITALIZATION OR DEATH, MORTALITY, WHO SCORE 7 AND ABOVE, AE, SAE Data not available for all or nearly all participants randomized No evidence that the result is not biased. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome due to similar proportions of missing data between arms. Risk assessed to be some concerns for the outcomes: Hospitalization or death. Mortality (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION In total, 100 participants were not analyzed for reasons stated above and unknown reasons for the remainder. Data not available for all or nearly all participants randomized No evidence that the result is not biased. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome Risk assessed to be some concerns for the outcomes: Incidence of viral negative conversion (D7). |
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, 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). HOSPITALIZATION OR DEATH, WHO SCORE 7 AND ABOVE For this outcome, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment. Risk assessed to be low for the outcomes: Hospitalization or death. WHO score 7 and above (D28). ADVERSE EVENTS and SERIOUS ADVERSE EVENTS The authors reported on adverse events and 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: Adverse events. Serious adverse events. |
Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, and prospective registry (dated April 22, 2020) were available.
HOSPITALIZATION OR DEATH. MORTALITY (D28). INCIDENCE OF VIRAL NEGATIVE CONVERION (D7). WHO SCORE 7 AND ABOVE (D28).ADVERSE EVENTS Outcomes pre-specified. Results were not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcome: Hospitalization or death. Mortality (D28). Incidence of viral negative conversion (D7). WHO score 7 and above (D28). Adverse events. SERIOUS ADVERSE EVENTS Outcome data acquired from direct contact with authors. Analysis performed by the COVID-NMA. Risk assessed to be low for the outcome: Serious adverse events. |
Overall risk of bias |
Some concerns |