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: “Patients were randomized to either APRV or LTV within 48 hours of endotracheal intubation.” [Report] Patients will be randomly allocated to either LTV or APRV group at 1:1 ratio. Such randomization will be performed by permuted blocks with length of 4; numbers will be generated by computer and patients will be sequentially numbered. Investigators assistants will recruit patients, will assign allocation groups, and will obtain informed consent from participants.” [Protocol]
Comment: Allocation sequence random. No information on allocation concealment. |
| Deviations from intervention |
Some concerns |
Quote: “None (Open Label) [Registry]; Due to logistic reasons and the nature of the intervention, only investigators and data analysts will be blinded.” [Protocol]
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: Patients were excluded from analysis because they died within 48 hours of randomization (APRV 3/51, 5.9%; LTV 3/50, 6.0%), were extubated within 48 hours of randomization (2/51, 3.9%; 2/50, 4.0%) or were lost to follow up (1/51, 2.0%; 0/50, 0.0%). Three patients on APRV and two on LTV were crossed over due to intractable hypoxemia, but were analyzed according to randomization. No information on administration of co-interventions of interest: antivirals and biologics. Corticosteroids were reported and balanced between groups. 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 some concerns for the outcomes: Mortality (D28). Time to Death. |
| Missing outcome data |
Low |
Comment: 101 participants randomized; 90 participants analyzed.
Data not available for all or nearly all participants randomized. Evidence that the result is not biased. Reasons: Non-differential missing data (similar proportion of and similar reasons for missing data in compared groups): Patients were excluded from analysis because they died within 48 hours of randomization (APRV 3/51, 5.9%; LTV 3/50, 6.0%), were extubated within 48 hours of randomization (2/51, 3.9%; 2/50, 4.0%) or were lost to follow up (1/51, 2.0%; 0/50, 0.0%). Risk assessed to be low for the outcomes: Mortality (D28). Time to death. |
| Measurement of the outcome |
Low |
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. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, supplementary appendices and registry (dated January 9, 2020) were available.
Outcome 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). Time to death. |
| Overall risk of bias |
Some concerns |