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: "Randomization was performed centrally. After the investigator entered the eligibility screening data, the central electronic system generated a unique subject identifer (subject ID) and a unique investigational product (IP) lot number."
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: "The investigator and patients were blinded to the treatment allocation. LVL and placebo were provided in identical primary and secondary packages with identical labels." (report) "Masking: Double (Participant, Investigator)" (registry)
Comment: Blinded study (participants and investigators). Our analysis for the binary outcomes are intention-to-treat analyses. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Clinical improvement (D28). Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 206 participants randomized; 206 participants analyzed for clinical improvement, 204 participants analyzed for the adverse events and mortality.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Clinical improvement (D28). Adverse events. Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Clinical improvement (D28). Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The registry was retrospective (dated May 21, 2020).
No information on whether the result was selected from multiple outcome measurements or analyses of the data. No information on whether the trial was analyzed as pre-specified. Risk assessed to be some concerns for the outcomes: Mortality (D28). Clinical improvement (D28). Adverse events. Serious adverse events. Mortality outcome was not pre-specified in the registry, however, we do not consider the reporting of this outcome at the end of follow-up to be selective since mortality should be reported even if not planned. Results were probably not selected from multiple outcome measurements or analyses of the data. Risk assessed to be low for the outcome: Mortality (D60 or more). |
| Overall risk of bias |
Some concerns |