| Bias | Author's judgement | Support for judgement |
| Randomization |
Some concerns |
Quote: "Randomization was centrally done using computer-generated sequences" “Initial dosing was done for first five patients in a staggered manner wherein after a patient was dosed, safety was monitored for 24-48 hours prior to dosing of the next patient. Once all five patients were dosed in this staggered manner, subsequent patients were enrolled such that study had patients randomized in a 2:1 ratio. Patients who were randomized, but did not receive the full infusion, were considered unevaluable and the same randomization code was used for allocation of the next patient enrolled by the study site."
Comment: Unclear whether allocation sequence was random for all patients included. 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. Antivirals and corticosteroids were sometimes given as part of the standard care treatment; it was not reported how many patients received these drugs. Hence no information on deviations that arose due to the trial context. To measure the effect of assignment to intervention, the method of analysis used was considered inappropriate; data were analyzed per protocol, excluding those who had not received at least one dose of the drug. There was not a substantial impact of the failure to analyze participants in their randomized groups (<10% difference) |
| Missing outcome data |
Low |
Comment: 32 patients randomized; 32 patients analyzed for mortality and safety; 30 patients analyzed for clinical improvement, WHO score 6 and above, and WHO score 7 and above.
Two patients were excluded from analysis of clinical improvement, WHO score 6 and above, and WHO score 7 and above due to non-receipt of drug; missingness is unlikely to be related to these outcomes. Risk assessed to be low for the outcomes: Mortality. Clinical improvement. WHO score 6 and above. WHO score 7 and above. Adverse events. Serious adverse events. |
| Measurement of the outcome |
Some concerns |
Comment: Appropriate method of measuring the outcomes.
Measurement or ascertainment of outcomes do not differ. Unblinded study (outcome assessor) Mortality is an observer-reported outcome not involving judgement. For WHO score 7 and above, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment. Risk assessed to be low for the outcomes: Mortality. WHO score 7 and above. Clinical improvement (defined as discharge) and WHO score 6 and above require clinical judgement and could be affected by knowledge of intervention receipt. Also, the authors reported on adverse events and serious adverse events that may contain both clinically- and laboratory-detected outcomes. All these outcomes 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: Clinical improvement. WHO score 6 and above. Adverse events. Serious adverse events. |
| Selection of the reported results |
Some concerns |
Comment: Neither the protocol nor the statistical analysis plan was available. The prospective trial registry was available. Data analyzed and presented as pre-specified.
Results for mortality, clinical improvement, WHO score 6 and above, and WHO score 7 and above 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. Clinical improvement. WHO score 6 and above. WHO score 7 and above. Adverse events and Serious adverse events were not pre-specified. No information on whether the results were selected from multiple outcome measurements or analyses of the data. Risk assessed to be some concerns for outcomes: Adverse events. Serious adverse events. |
| Overall risk of bias |
Some concerns |