| 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: randomization process described, Allocation sequence random and 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: staff delivering and assessing the intervention are aware of the treatment allocation. Participants were analyzed according to their assigned intervention. No information on administration of co-interventions of interest: corticosteroids, antivirals and biologics. |
| Missing outcome data |
Low |
Quote: "Two
patients (one in the HDIVC group and one in the placebo group) were excluded due to the treatment
period of less than three days due to death."
Comment: 56 randomized, 54 analyzed. All missing data occurred due to documented reasons related to the outcome, Mortality. However data is available for >95% of population. Risk assessed to be low for outcomes: Mortality. Time to death. |
| Measurement of the outcome |
Low |
Comment: Unblinded study. Appropriate method of outcome measurement.
Mortality is an observer-reported outcome not involving judgement. Measurement of outcome does not differ between groups. Risk assessed to be low for outcomes: Mortality. Time to death. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan and prospective registry were available.
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. Time to death. |
| Overall risk of bias |
Some concerns |