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: “Randomization will be performed by an online web-based central using a pre-prepared randomization list, stratified by center and by the time of IMV on randomization: less than 12 hours, between 12 and
24 hours, and between 24 and 36 hours, balanced by randomly variable block size (2 and 4). The group treatment is disclosed to the investigator only after all information regarding patient enrolment is recorded in the online system.”
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: “Double-blind. Trial participants, care providers, and outcome assessors were masked to patient assignment. The double-blinding was provided by each hospital pharmacy, using opaque sleeves and tubing to conceal the product administered. To preserve the masking, research nurses supervised the administration and were asked not to disclose whether IVIG or placebo was infused. Masking was removed in the event of an adverse effect that could be attributed to IVIG or placebo and upon the responsible investigator's approval. The statisticians who analysed the data were masked to group assignment.”
Of note, three adverse events led to unmasking in the placebo group. Comment: Probably partially blinded study (participants and personnel/carers) Deviations from intended intervention arising because of the study context: No participant cross-over. Administration of co-interventions of interest: antivirals, biologics and corticosteroids balanced between groups. Hence, deviations did not arise because of the trial context. Our analysis for the outcome is an intention-to-treat analysis. This method was considered appropriate to estimate the effect of assignment to intervention. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Clinical improvement (D28). Clinical improvement (D60 or more). Time to clinical improvement. WHO score 7 and above (D28). WHO score 7 and above (D60 or more). Adverse events. Serious adverse events. |
| Missing outcome data |
Low |
Comment: 146 participants randomized; 144 participants analyzed.
Data available for all or nearly all participants randomized. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Clinical improvement (D28). Clinical improvement (D60 or more). Time to clinical improvement. WHO score 7 and above (D28). WHO score 7 and above (D60 or more). Adverse events. Serious adverse events. |
| Measurement of the outcome |
Low |
Comment: Method of measuring the outcome probably appropriate.
Measurement or ascertainment of outcome probably does not differ between groups. Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Time to death. Clinical improvement (D28). Clinical improvement (D60 or more). Time to clinical improvement. WHO score 7 and above (D28). WHO score 7 and above (D60 or more). Adverse events. Serious adverse events. |
| Selection of the reported results |
Low |
Comment: The protocol, statistical analysis plan, registry were available. Registration posted in EudraCT on April 6th 2020, only 2 days into a 6-month recruitment period
MORTALITY. ADVERSE AND SERIOUS ADVERSE EVENTS. Outcomes 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). Mortality (D60 or more). Adverse events. Serious adverse events. CLINICAL IMPROVEMENT, TIME TO CLINICAL IMPROVEMENT, TIME TO DEATH, WHO SCORE 7 AND ABOVE Outcome data acquired from contact with authors. Results were probably not selected from multiple outcome measurements or analyses of the data. Trial analyzed as pre-specified. Risk assessed to be low for the outcome: Time to death. Clinical improvement (D28). Clinical improvement (D60 or more). Time to clinical improvement. WHO score 7 and above (D28). WHO score 7 and above (D60 or more). |
| Overall risk of bias |
Low |