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: "...randomise participants into the 4 arms 1:1:1:1 using a centralised concealed online process to assign participants to a medication kit number."
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: “Double-blind (investigators and participants).”
Comment: Blinded study (participants and personnel/carers) HOSPITALIZATION OR DEATH. MORTALITY. WHO SCORE 7 AND ABOVE. ADVERSE AND SERIOUS ADVERSE EVENTS. 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). WHO score 7 and above (D28). Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION Participants were analyzed according to their randomized groups for the outcome. Of note, 32 participants were excluded from the analysis post-randomization because of undectable viral loads at both Day 1 and Day 5. Nevertheless, this method was considered appropriate to estimate the effect of assignment to intervention for this outcome. Risk assessed to be low for the outcome:Incidence of viral negative conversion (D7). |
| Missing outcome data |
Some concerns |
Comment: 240 participants randomized; 227 participants analyzed for Hospitalization or death / WHO score 7 and above / Mortality / SAE; 224 participants analyzed for negative conversion.
Data not available for all participants randomized. No evidence that the result is not biased. Reasons: 16/1/14/0 withdrawn due to toxicity; 2/0/1/1 stopped investigational product; 0/0/1/0 lost to follow up; 1/1/1/0 withdrawn due to SAE. 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: Hospitalization or death. Mortality (D28). WHO score 7 and above (D28). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Blinded study (outcome assessor). 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. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, and prospective registry were available (dated Aug 5, 2020).
HOSPITALIZATION OR DEATH. MORTALITY. VIRAL NEGATIVE CONVERSION. ADVERSE AND SERIOUS ADVERSE EVENTS. Outcome 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). Adverse events. Serious adverse events. WHO SCORE 7 AND ABOVE Outcome data acquired from direct contact with authors. Analysis performed by the COVID-NMA. Risk assessed to be low for the outcome: WHO score 7 and above (D28). |
| Overall risk of bias |
Some concerns |