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: “A centralized electronic system was used to randomly assign enrolled patients to receive CCP or placebo in a 1:1 ratio stratified by enrollment site and risk status using randomization block sizes of 4 and 6 to maintain balanced group sizes. Allocation was concealed.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Low |
Quote: “Patients, treating clinicians, trial personnel, and outcome assessors were blinded to group assignment.”
Comment: Blinded study (participants and personnel/carers) 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. Of note, 1 vs 1 participants were excluded from the analysis post-randomization because they no longer met eligibility criteria and 0 vs 1 participants were excluded due to product dispensing error. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Clinical improvement (D28). WHO score 7 or above (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
Some concerns |
Comment: 941 participants randomized; 941 participants analyzed for safety; 924 participants analyzed for mortality; 728 participants analyzed for negative conversion, clinical improvement and WHO score 7 or above.
MORTALITY. ADVERSE AND SERIOUS ADVERSE EVENTS Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION. CLINICAL IMPROVEMENT. WHO SCORE 7 AND ABOVE. No evidence that the result is not biased. Reasons: Outcome data were not available for all participants for ordinal scale at D28. Missingness could depend on the true value of the outcome. Not likely that missingness depended on the true value of the outcome as the proportions missing are balanced between arms. Risk assessed to be some concerns for the outcomes: Incidence of viral negative conversion (D7). Clinical improvement (D28). WHO score 7 or above (D28). |
| 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: Mortality (D28). Incidence of viral negative conversion (D7). Clinical improvement (D28). WHO score 7 or above (D28). Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, registry were available (dated April 22, 2020).
Outcomes pre-specified in registry and/or protocol. 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 outcomes: Mortality (D28). Incidence of viral negative conversion (D7). Clinical improvement (D28). WHO score 7 or above (D28). Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |