Trial NCT04435795
Publication CONTAIN - Ezer N, BMJ (2021) (published paper)
Primary outcome on the report: Resolution of self-reported fever and all respiratory symptoms at day 7 of treatment. Respiratory symptoms included cough (wet or dry) or dyspnoea (which included the description of shortness of breath, chest congestion, or chest tightness as synonyms).

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: “Randomisation was done centrally at the research pharmacy of the McGill University Health Centre in Montreal, Canada. The trial statistician generated a permuted block randomisation sequence using variably sized blocks of 2, 4, 6, and 8, with stratification according to sex. An unblinded research assistant sequentially assigned participants. The assignments were concealed from investigators and participants; only pharmacies and a central research assistant had access to the treatment allocation.”
Comment: Allocation sequence random.
Allocation sequence concealed.
Deviations from intervention
Low 		Quote: “double-blinded; Investigators, participants, and statisticians were blinded to treatment allocation.”
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: Hospitalization or death. Mortality (D28). Adverse events. Serious adverse events.
Missing outcome data
Some concerns 		Comment: 215 participants randomized; 203 participants analyzed for hospitalization and death, and 209 participants analyzed for safety.

HOSPITALIZATION OR DEATH. MORTALITY.
Data not available for all or nearly all participants randomized.
No evidence that the result is not biased.
Reasons: discontinuation of treatment (treatment= 1, placebo = 3), lost to follow up (1, 3), withdrew (0, 3), took an off-label inhaled steroid (1, 0).
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).

ADVERSE AND SERIOUS ADVERSE EVENTS.
Data available for all or nearly all participants randomized.
Risk assessed to be low for the outcomes: 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). Adverse events. Serious adverse events.
Selection of the reported results
Low 		Comment: The registry was available (dated June 17, 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: Hospitalization or death. Mortality (D28). Adverse events. Serious adverse events.
Overall risk of bias
Some concerns