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: "2:1 (SpiroDex:Dex) randomisation was performed utilising a coin toss method to achieve the desired probability The group allocation was known only to the treating non-trial physician. The patients and the trial investigators were blinded to group allocation."
Comment: Allocation sequence random. No information on allocation concealment. |
| Deviations from intervention |
Some concerns |
Quote: "group allocation was known only to the treating non-trial physician. The patients and the trial investigators were blinded".
Comment: Unblinded study (participants blinded; physician unblinded). Deviations from intended intervention arising because of the study context: No participant cross-over. No information on administration of co-interventions of interest: antivirals and biologics. All received corticosteroids. Hence, no information on whether deviations arose because of the trial context. 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 some concerns for the outcomes: Clinical improvement (D28). |
| Missing outcome data |
High |
Comment: 120 participants randomized; 120 participants analyzed; 30 participants (25%)with missing data.
Data not available for all participants randomized. No evidence that the result is not biased. Reasons: 19% vs 35% total missing in the intervention vs control groups, respectively: 5% vs 20% due to worsening COVID, 7% vs 13% left hospital and transferred to separate facility, 1% vs 2% lost to follow-up, 4% vs 0% consent withdrawn, 1% vs 0% discharged and did not complete day 28 cough score. Missingness could depend on the true value of the outcome. Likely that missingness depended on the true value of the outcome. Risk assessed to be high for the outcomes: Clinical improvement (D28). |
| Measurement of the outcome |
Some concerns |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Unblinded study (outcome assessor). CLINICAL IMPROVEMENT Clinical improvement [defined as Discharge alive by day 28 and without clinical deterioration during the trial (i.e., without reaching WHO ordinal scale >4)] requires clinical judgement and could be affected by knowledge of intervention receipt, but it is not considered likely to in the context of a pandemic. Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). |
| Selection of the reported results |
Some concerns |
Comment: The registry was retrospective (dated March 4, 2021).
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: Clinical improvement (D28). |
| Overall risk of bias |
High |