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: "All patients were centrally randomized to the study using an interactive web response system, which linked a sequential patient randomization number to the treatment codes. The randomization numbers were blocked, and within each block the
prespecified ratio of patients was allocated to each group."
Comment: Allocation sequence random Allocation sequence concealed Imbalances in baseline characteristics appear to be compatible with chance |
| Deviations from intervention |
Some concerns |
Quote: “This study will be double-blind, and will remain blinded to the investigator, all designated study staff (with the exception of the unblinded study pharmacists or unblinded staffs designated to prepare the study drug for infusion and predefined unblinded teams in the sponsor and CRO), and patients until the final CSR is generated [FROM PROTOCOL].”
Comment: Blinded study (participants and personnel/carers) HOSPITALIZATION OR DEATH. MORTALITY. 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). Mortality (D60 or more). Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION Participants were analyzed according to their randomized groups for the outcome viral negative conversion. Of note, 44 vs 41 participants were excluded from the analysis post-randomization because they were diagnosed with COVID-19 by sponsor-supplied rapid antigen kit rather than quantitative RT-PCR at day 1 (40 vs 32) or did not receive the study drug (4 vs 9). This method was considered inappropriate to estimate the effect of assignment to intervention for this outcome. There was probably no substantial impact of failure to analyze participants according to their randomized groups. Risk assessed to be some concerns for the outcome: Incidence of viral negative conversion (D7). |
| Missing outcome data |
Low |
Comment: 1315 participants randomized; 1315 participants analyzed for mortality; 1302 participants analyzed for safety (<1% missing data) ; 1230 participants analyzed for negative conversion (1% missing data).
HOSPITALIZATION OR DEATH. MORTALITY. ADVSERSE AND SERIOUS ADVERSE EVENTS. Data available for all or nearly all participants randomized for mortality and safety. Risk assessed to be low for the outcomes: Hospitalization or death. Mortality (D28). Mortality (D60 or more). Adverse events. Serious adverse events. VIRAL NEGATIVE CONVERSION Data not available for all or nearly all participants randomized for negative conversion. No evidence that the result is not biased. Reasons: 4 vs 9 did not receive the drug. This was accounted for in domain 2. Risk assessed to be low for the outcomes: Incidence of viral negative conversion (D7). |
| 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). Mortality (D60 or more). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, registry were available (dated October 26, 2020)
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). Mortality (D60 or more). Incidence of viral negative conversion (D7). Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |