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: “Block randomization was done using a computer-generated list and a block size of 4. Randomization and preparation of study medication were performed centrally.”
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
Deviations from intervention |
Low |
Quote: "None of the researchers, treating physicians or participants was aware of the participant group allocation throughout the duration of the 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). |
Missing outcome data |
Low |
Comment: 1083 participants randomized; 1083 participants analyzed.
Data available for all or nearly all participants randomized (4% missing data). Of note, 5 vs 4 withdrew consent, 15 vs 6 were self discharged, 3 vs 3 discontinued intervention, 2 vs 1 had nausea, 1 vs 0 had atrial fibrillation, 0 vs 1 had a mycordial infarction and 0 vs 1 had intestinal obstruction. Risk assessed to be low for the outcomes: Mortality (D28). Clinical improvement (D28). |
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). |
Selection of the reported results |
Some concerns |
Comment: The prospective registry was available (dated, July 5th, 2020).
MORTALITY Mortality outcome was not pre-specified in the registry, however, we do not consider the reporting of this outcome to be selective since mortality should be reported even if not planned. Results for mortality were probably not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified for mortality. Risk assessed to be low for the outcome: Mortality (D28). CLINICAL IMPROVEMENT The clinical improvement outcome extracted (hospital discharge) is described as “recovery” in the report and the registry. While discharge is included in definitions of the recovery outcome in the report, in the registry recovery is defined only in terms of symptoms. No information on whether the result on clinical improvement 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). |
Overall risk of bias |
Some concerns |