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: "Patients were randomized in permuted blocks of 4 in a randomization sequence prepared by the unblinded pharmacist in Microsoft Excel version 19.0 who provided masked ivermectin or placebo to a field nurse for home or hospital patient visits. Allocation assignment was concealed from investigators and patients."
Comment: Allocation sequence random. Allocation sequence concealed. Imbalances in baseline characteristics appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Registry: “Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)”
Comment: Blinded study (participants and personnel/carers)
MORTALITY, CLINICAL IMPROVEMENT, WHO SCORE 7 AND ABOVE, AE, SAE 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 low for the outcomes: Mortality (D28). Mortality (D60 or more). Clinical improvement (D28). WHO score 7 and above (D28). WHO score 7 and above (D60 or more). Adverse events. Serious adverse events. TIME TO CLINICAL IMPROVEMENT Participants were analyzed according to their randomized groups for the outcome. Of note, due to a labeling error, 38 participants randomized to placebo were given the study drug. All participants randomized during this time period (n=75) were excluded from the primary analysis. Study authors present as-treated results in supplementary files. 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 clinical improvement. |
| Missing outcome data |
Low |
Comment: 476 participants randomized; 398 participants analyzed.
Data not available for all or nearly all participants randomized. No evidence that the result is not biased. Reasons for missing data: error in labeling, which resulted in 38 placebo group participants receiving treatment. All participants (n=75) randomized during this period were removed from the primary analysis. Furthermore, 3 participants were also excluded from analysis due to meeting exclusion criteria identified post-randomization. Hence, missingness due to documented reasons unrelated to true value of the outcome. Risk assessed to be low for the outcomes: Mortality (D28). Mortality (D60 or more). Clinical improvement (D28). 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). Clinical improvement (D28). 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 |
Some concerns |
Comment: The protocol (dated June 9th, 2020), statistical analysis plan (dated May 12th, 2020), registry (up to the July 20th, 2020 version) were consulted.
MORTALITY (D28), WHO SCORE 7 AND ABOVE (D28), AE, SAE Outcome pre-specified. Results were not selected from multiple outcome measurements or analyses of the data. Primary outcome modified during the conduct of the trial, but reason was provided. Trial analyzed as pre-specified. Risk assessed to be low for the outcome: Mortality (D28). WHO score 7 and above (D28). Adverse events. Serious adverse events. (TIME TO) CLINICAL IMPROVEMENT Outcome not pre-specified (added as an outcome at a later date [retrospective]) No information on whether the result was selected from multiple outcome measurements or analyses of the data. Trial probably not analyzed as pre-specified. Risk assessed to be some concerns for the outcomes: Clinical improvement (D28). Time to clinical improvement. MORTALITY (D60 OR MORE), WHO SCORE 7 AND ABOVE (D60 OR MORE) 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: Mortality (D60 or more). WHO score 7 and above (D60 or more). |
| Overall risk of bias |
Some concerns |