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: “Randomised, double-blind, placebo-controlled, multiple-ascending-dose trial.”
Comment: Allocation sequence probably random. No information on allocation concealment. |
Deviations from intervention |
Low |
Quote: “Randomised, double-blind, placebo-controlled, multiple-ascending-dose trial.”
Comment: Blinded study (participants and personnel/carers) 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 low for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
Missing outcome data |
Low |
Comment: 25 participants randomized; 24 participants analyzed for efficacy, 25 for safety.
Data available for all or nearly all of population. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. |
Selection of the reported results |
Some concerns |
Comment: The retrospective versions of the protocol and statistical analysis plan were available. The EU Clinical Trials Register was available as well but retrospective (dated July 29th, 2020). The prospective versions of the registry on clinicaltrials.gov were accessible and consulted however only the Part 2 study outcomes were pre-specified.
CLINICAL IMPROVEMENT. WHO SCORE 7 AND ABOVE. ADVERSE AND SERIOUS ADVERSE EVENTS. Part 1 study outcomes were not pre-specified in the registry. 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: Clinical improvement (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. MORTALITY Mortality outcome was not pre-specified, however, we do not consider the reporting of this outcome 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 (D28). |
Overall risk of bias |
Some concerns |