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: "Each ICU was assigned with an independent random numeric table generated by Microsoft Excel 2019 by
the primary investigator alone. Each table had equal numbers of 1 and 2, which represented the placebo
group (bacteriostatic water infusion) and treatment group (HDIVC), respectively. The generated random
list was stored by the principal investigator who was not involved in the treatment of patients and hidden
to the other investigators. When a patient was transferred to the ICU and met the enrolment criteria, the
clinician on duty would inform the principal investigator and obtain a number from the list. Then,
participants were enrolled in the corresponding group according to the chronological order of ICU
recruitment. The grouping and intervention were unknown to the participants and investigators who were
responsible for data collection and statistical analysis"
Comment: Allocation sequence random. Allocation sequence probably concealed. |
| Deviations from intervention |
Some concerns |
Quote: "The study is unblinded for dosing nurses, attending physicians and investigators in charge of enrolling participants, but blinding will be maintained for patients and all other members of the clinical and research team, such as statistical staff, to minimise bias."
Comment: Participants blinded. Personnel/carers unblinded. Deviations from intended intervention arising because of the study context: No participant cross over. No information on administration of co-interventions of interest: corticosteroids, antivirals and biologics. Hence, no information on whether deviations arose because of the trial context. 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: 56 participants randomized, 56 participants analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for 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 is an observer-reported outcome not involving judgement. Risk assessed to be low for outcomes: Mortality (D28). Time to death. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan and registry were available. The original February 8th, 2020 version of the registry was utilized as this was considered to be acceptable for assessing pre-specification of outcomes and selection of reported result (study start date February 2nd, 2020).
Mortality outcome was pre-specified. Result was 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 was not pre-specified. No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified. Risk assessed to be some concerns for the outcome: Time to death. |
| Overall risk of bias |
Some concerns |