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: "Randomisation was performed by a computerised random number generator, and allocation was concealed in sealed opaque paper envelopes. While the attending medical team recruited patients, obtained consent and documented the clinical data, a separate trial team administered the inhaled nitric oxide and trial allocation envelopes were opened by the latter."
Comment: Allocation sequence random. Allocation sequence probably concealed. |
| Deviations from intervention |
Some concerns |
Quote: "Open-label"
Comment: Unblinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. No information on administration of co-interventions of interest: Biologics, antivirals. All participants received corticosteroids. Hence, no information on whether deviations arose because of the trial context. Data for the outcome were analyzed using 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: Mortality (D28). Incidence of viral negative conversion (D7). Clinical improvement (D28). |
| Missing outcome data |
High |
Comment: 29 participants randomized; 25 participants analyzed.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons: 4 patients in the control group withdrew consent. Missingness could depend on the true value of the outcome. Likely that missingness depended on the true value of the outcome (imbalance of missing data between arms). Risk assessed to be high for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). 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) MORTALITY, VIRAL NEGATIVE CONVERSION Mortality and viral negative conversion are observer-reported outcomes not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Incidence of viral negative conversion (D7). CLINICAL IMPROVEMENT Clinical improvement (defined as improvement of ≥2 points on the WHO Ordinal Scale) requires clinical judgement and could be affected by knowledge of intervention receipt, but it 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 trial registry was retrospective (dated March 11th, 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: Mortality (D28). Incidence of viral negative conversion (D7). Clinical improvement (D28). |
| Overall risk of bias |
High |