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: "A completely blocked randomized design to
form the allocation list for the two comparison groups.
A computer random number generator was used to build
random permuted blocks with a block size of four and
an equal allocation ratio. The randomization process
was carried out by the designated blinded investigator,
who did not acknowledge the treatment assignment."
Comment: Allocation sequence random Allocation sequence concealed |
| Deviations from intervention |
Some concerns |
Quote: “Single blinding. The randomization process was carried out by the designated blinded investigator, who did not acknowledge the treatment assignment. The
study statistics team was also blinded to elaborate interim analysis and safety reports. Both participants and the clinical research team were unblinded to the treatment
assignment.”
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: corticosteroids. Antivirals and biologics were not allowed. Hence, no information on whether deviations arose because of the trial context. MORTALITY. CLINICAL IMPROVEMENT. ADVERSE AND SERIOUS ADVERSE EVENTS. 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: Mortality (D28). Clinical improvement (D28). Adverse events. Serious adverse events. TIME TO DEATH. TIME TO CLINICAL IMPROVEMENT Participants were analyzed according to their randomized groups for the outcome. Of note, 2/50 and 4/51 participants were excluded from the analysis post-randomization because they did not receive their assigned treatment; 1/50, 0/51 did not meet inclusion criteria; 1/50, 0/51 received non-super donor CP. This method was considered inappropriate to estimate the effect of assignment to intervention for this outcome. There was probably no substantial impact of failure to analyze participants according to their randomized groups. Risk assessed to be some concerns for the outcomes: Time to death. Time to clinical improvement. |
| Missing outcome data |
Some concerns |
Comment: 101 participants randomized; 91 participants analyzed.
MORTALITY. CLINICAL IMPROVEMENT. ADVERSE AND SERIOUS ADVERSE EVENTS Data not available for all participants randomized. No evidence that the result is not biased. Reasons that were not addressed in domain 2: 2/50 and 4/51 participants were excluded from the analysis post-randomization because they did not receive their assigned treatment; 1/50, 0/51 did not meet inclusion criteria; 1/50, 0/51 received non-super donor CP. 0/50 and 2/51 were lost to follow up due to transfer to another facility. Missingness could not depend on the true value of the outcome as the reason is due to outside factors. Risk assessed to be some concerns for the outcomes: Mortality (D28). Clinical improvement (D28). Adverse events. Serious adverse events. TIME TO DEATH. TIME TO CLINICAL IMPROVEMENT Data available for nearly all participants randomized. Of note, 8 of the 10 missing participants were addressed in domain 2; 0 vs 2 were lost to follow up. Risk assessed to be low for the outcomes: Time to death. 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 (outcome assessor) OR Unclear blinding (outcome assessor). MORTALITY, TIME TO DEATH Observer-reported outcome not involving judgement. Risk assessed to be low for the outcomes: Mortality (D28). Time to death. (TIME TO) CLINICAL IMPROVEMENT Clinical improvement (defined as discharge or reduction in 2 points in 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). Time to clinical improvement. ADVERSE and SERIOUS ADVERSE EVENTS The authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected events, which can be influenced by knowledge of the intervention assignment, but is not likely in the context of the pandemic. Risk assessed to be some concerns for the outcomes: Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The prospective registry was available (dated April 3, 2020).
Outcome pre-specified. 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 outcome: Mortality (D28). Time to death. Clinical improvement (D28). Time to clinical improvement. Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |