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.
|Support for judgement
|Quote: “Randomization was centrally performed through a web-based system using computer-generated random numbers with blocks of 2 and 4, unknown to the investigators, and was stratified by study site to ensure allocation concealment.”
Comment: Allocation sequence random.
Allocation sequence concealed.
|Deviations from intervention
Comment: Unblinded study (participants and personnel/carers)
Deviations from intended intervention arising because of the study context:
No participant cross-over: One patient randomized to conventional oxygen therapy received high-flow oxygen therapy according to the decision of the attending physician. This patient was analyzed in the conventional oxygen therapy group.
Information on administration of co-interventions of interest: antivirals, corticosteroids and biologics were reported and balanced.
Hence, deviations did not arise because of the trial context.
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). Time to death. Clinical improvement (D28). Time to clinical improvement.
|Missing outcome data
|Comment: 220 participants randomized; 199 participants analyzed for mortality; 212 participants analyzed for clinical improvement.
Data available for nearly all participants randomized for clinical improvement.
Data not available for all or nearly all participants randomized for mortality.
No evidence that the result is not biased.
Reasons:6/109 and 7/111 transferred to a non-participating hospital; 4/109 and 4/111 withdrew consent.
Missingness could depend on the true value of the outcome.
Not likely that missingness depended on the true value of the outcome due to similar proportions of missing data between arms.
Risk assessed to be some concerns for the outcomes: Mortality (D28). Time to death. Clinical improvement (D28). Time to clinical improvement.
Risk assessed to be low for the outcomes: Clinical improvement (D28). Time to clinical improvement.
|Measurement of the outcome
|Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups.
Unblinded study (outcome assessor)
MORTALITY, TIME TO DEATH
Observer-reported outcome not involving judgement.
Risk assessed to be low for the outcomes: Mortality (D28). Time to death.
(TIME TO) CLINICAL IMPROVEMENT
Clinical improvement (defined as reduction in two or more points in the modified ordinal 7-category scale) requires clinical judgement and could be affected by knowledge of intervention receipt, but it not considered likely to in the context of a pandemic.
Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). Time to clinical improvement.
|Selection of the reported results
|Comment: The prospective protocol (dated July 15, 2020), statistical analysis plan, supplemental appendices and retrospective registry (dated Oct 28, 2020) were available.
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). Time to death. Clinical improvement (D28). Time to clinical improvement.
|Overall risk of bias