Trial NCT04342663
Publication Lenze E, JAMA (2020) (published paper)
Primary outcome on the report: Clinical deterioration: (1) presence of dyspnea (ie, shortness of breath) or hospitalization for shortness of breath or pneumonia and (2) decrease in O2 saturation (<92%) on room air or supplemental O2 requirement to maintain O2 saturation of >= 92%

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: “Randomization schedules were generated that stratified by age (18-44, 45-54, 55-64, and ≥65 years) and sex. Treatments were randomly allocated using alternating block sizes of 2 and 4. Randomization allocation was conducted via REDCap, which displayed randomization assignment to the laboratory manager (J.S.), who prepared the study materials, including the study drug or placebo”
Comment: Allocation sequence random. Allocation sequence concealed.
Deviations from intervention
Low 		Quote: “double-blind”
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.
Risk assessed to be low for the outcomes: Mortality (D28). Hospitalization or death. WHO score 7 and above (D28). Serious Adverse Events.
Missing outcome data
Some concerns 		Comment: 181 participants randomized; 152 participants analyzed.
Data not available for all or nearly all participants randomized.
No evidence that the result is not biased.
Reasons: could not confirm eligibility at baseline (7 vs 9), oxygen saturation <92% at baseline (2 vs 2), withdrew from study prior to receiving medication (3 vs 6).
Missingness could depend on the true value of the outcome.
Not likely that missingness depended on the true value of the outcome (same reasons for missingness and proportion balanced between arms).
Risk assessed to be some concerns for the outcomes: Mortality (D28). Hospitalization or death. WHO score 7 and above (D28). 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. WHO score 7 and above (D28). Serious adverse events.
Selection of the reported results
Low 		Comment: The prospective protocol (April 9, 2020), statistical analysis plan, registry were available (dated April 13, 2020).
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: Mortality (D28). Hospitalization or death. WHO score 7 and above (D28). Serious Adverse Events.
Overall risk of bias
Some concerns