Trial NCT04343768
Publication COVIFERON - Darazam IA, Scientific Reports (2021) (published paper)
Primary outcome on the report: Our primary outcome measure was TTCI [time to clinical improvement], defined as the time from enrollment to discharge from the hospital or a decline of two steps on the seven-step ordinal scale. (I) Not hospitalized, and has no activity limitations; (II) Not hospitalized, but has activity limitations; (III) Hospitalized, but does not need any supplemental oxygen; (IV) Hospitalized, and needs supplemental oxygen; (V) Hospitalized, and needs either High-Flow Nasal Cannula (HFNC) or non-invasive ventilation; (VI) Hospitalized, and needs invasive ventilation; and (VII) Dead

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: “The permuted block(three or six patients per block) randomization sequence was generated using Package ‘randomizeR’ in R software version 3·6·1 and placed in individual sealed and opaque envelopes for allocation concealment by an outside statistician.”
Comment: Allocation sequence random. Allocation sequence concealed.
Deviations from intervention
Some concerns 		Quote: “Open-label”
Comment: Unblinded study.
No participant cross-over.
No information on administration of co-interventions of interest: Biologics and corticosteroids. Antivirals were reported and balanced between groups.Hence, no information on whether deviations arose because of the trial context.
Data were analyzed using intention-to-treat analysis.
Risk assessed to be low for the outcomes: Mortality (D28). Time to clinical improvement.
Missing outcome data
Low 		Comment: 60 patients randomized; 60 patients analyzed.
Data available for all or nearly all participants.
Risk assessed to be low for the outcomes: Mortality (D28). Time to clinical improvement.
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
Mortality is an observer-reported outcomes not involving judgement.
Risk assessed to be low for the outcome: Mortality (D28).
Clinical improvement (defined as the time from enrollment to discharge from the hospital or a decline of two steps on the seven-step ordinal scale) requires clinical judgement and could be affected by knowledge of intervention receipt.
Risk assessed to be some concerns for the outcome: Time to clinical improvement.
Selection of the reported results
Low 		Comment: The protocol and retrospective registry were available.
Results were not selected from multiple outcome measurements or analyses of the data.
Trial analyzed as pre-specified.
Risk assessed to be low for the outcomes: Mortality (D28). Time to clinical improvement
Overall risk of bias
Some concerns