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 |
Some concerns |
Quote: "Randomization was performed with an allocation ratio of 1:1 and a block size of eight. Randomization allocation was obtained via a centralized web-based system. Due to the nature of the intervention, the patient, the treating physician, care providers, data collectors and outcome assessors were aware of the allocation."
Comment: Allocation sequence random. Unclear allocation concealment (fixed block in open label trial). |
| Deviations from intervention |
Some concerns |
Quote: "the patient, the treating physician, care providers, data collectors and outcome assessors were aware of the allocation."
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No information on administration of co-interventions of interest reported: antivirals, biologics and corticosteroids. No information on participant cross-over but probable since in the control group "APP was not encouraged but could be prescribed by the attending clinician at his/her discretion" and "APP was increasingly considered standard of care in COVID-19 related hypoxic respiratory failure attenuating the difference in duration of APP between groups". This deviation could affect the outcome. Nevertheless, this domain was rated as some concern as it is impossible to distinguish deviation because of trial context and deviation because of intervention effect. Data for the outcome were analyzed using intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be some concerns for the outcomes: Mortality (D28). Time to death. |
| Missing outcome data |
Low |
Comment: 75 participants randomized; 75 participants analyzed.
Data available for all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. |
| Measurement of the outcome |
Low |
Quote: "the patient, the treating physician, care providers, data collectors and outcome assessors were aware of the allocation."
Comment: Method of measuring the outcome probably appropriate. Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor) Mortality is an observer-reported outcome not involving judgement. Risk assessed to be low for the outcome: Mortality (D28). Time to death. |
| Selection of the reported results |
Low |
Comment: The prospective protocol (dated 15th May 2020) and registry (dated 15th June 2020) were available. The statistical analysis plan was not available.
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 outcomes: Mortality (D28). Time to death. |
| Overall risk of bias |
Some concerns |