Trial NCT04504032
Publication Ananworanich J, Clin Infect Dis, 2021
Primary outcome on the report: Safety: frequency of adverse events (AEs) including Grades 3 and 4, resulting in discontinuation, serious AEs and hypersensitivity and major bleeding events through Day 35. Efficacy: the proportion of participants who progressed to moderate or severe disease category (Gates MRI scale 3 or higher), through Day 28.

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: “The study was conducted virtually at all study sites (virtual site and outpatient clinics) utilizing a telemedicine platform for screening and study visits (Decentralized Clinical Trial Operating SystemTM). Participants were randomized 1:1, stratified by site and symptom duration.”
Comment: Allocation sequence probably random. Allocation sequence concealed
Imbalances in baseline characteristics appear to be compatible with chance.
Deviations from intervention
Low 		Quote: “Masking: Triple (Participant, Investigator, Outcomes Assessor)”
Comment: Blinded study (participants and personnel/carers)
Our analysis for the binary outcomes 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: Mortality (D28). Hospitalization or death. Adverse events. Serious adverse events.
Missing outcome data
Some concerns 		Comment: 497 participants randomized; 420 participants analyzed (completed the study) for efficacy; 449 participants analyzed for safety/mortality.
Data not available for all or nearly all participants randomized.
No evidence that the result is not biased.
Reasons (efficacy analyses): COVID worsened pre-dosing (6.1% vs 1.2%), participant terminated (3.7% vs 4.4%), lost to follow up (2.4% vs 3.4%), non-compliance (0.8% vs 0%), sponsor terminated (0.4% vs 0.8%), adverse event (0.4% vs 0.8%), COVID worsened day 1 after product (0.4% vs 0%), investigational product arrived late (0.4% vs 0.4%).
Missingness could depend on the true value of the outcome.
Not likely that missingness depended on the true value of the outcome (similar proportion of missingness between arms).
Risk assessed to be some concerns for the outcomes: Mortality (D28). Hospitalization or death. 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: Mortality (D28). Hospitalization or death. Adverse events. Serious adverse events.
Selection of the reported results
Low 		Comment: The protocol, statistical analysis plan, registry (August 7, 2020) were available.
Safety outcomes pre-specified, including mortality.
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). Hospitalization or death. Adverse events. Serious adverse events.
Overall risk of bias
Some concerns