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: Eligible patients were randomized centrally, utilizing a dedicated software (http://www.randomization.com) and the results were utilized to label flasks containing 20 tablets (200 mg each) of the experimental drug and the identically appearing and packed sucrose placebo.
Comment: Allocation sequence random. Allocation sequence concealed. |
| Deviations from intervention |
Low |
Quote: "double-blinding"
Comment: Blinded study (physicians and outcome assessors) Data 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 outcome: Symptomatic confirmed COVID-19. Hospital admissions or death. ICU admissions or death. Mortality. Adverse events. |
| Missing outcome data |
Some concerns |
Comment: 130 participants randomized; 127 participants analyzed.
Of note, participants did not receive intervention due to positice basal PCR for SARS-CoV2 (3 vs 0), subjects were lost to follow up (14 vs 11), discontinued intervention: due to adverse reaction (4 vs 4), due to forgetfulness (0 vs 1), due to presenting COVID-19 (1 vs 6). Data not available for all participants randomized. No evidence that the result is not biased. Missingness could depend on the true value of the outcome Not likely that missingness depended on the true value of the outcome (equal proportion of missingness in both arms) Risk assessed to be some concerns for the outcome: Symptomatic confirmed COVID-19. Hospital admissions or death. ICU admissions or death. Mortality. 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: Symptomatic confirmed COVID-19. Hospital admissions or death. ICU admissions or death. Mortality. Adverse events. |
| Selection of the reported results |
Some concerns |
Comment: The prospective trial registry was available (up to version dated April 15th, 2020).
SYMPTOMATIC CONFIRMED COVID 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 outcomes: Symptomatic confirmed COVID-19. ADVERSE EVENTS Outcome not pre-specified. 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: Adverse events. |
| Overall risk of bias |
Some concerns |