| Bias | Author's judgement | Support for judgement |
| Randomization |
Low |
Quote: "Patients were randomly assigned (1:1) to either
azithromycin plus standard of care or standard of
care alone. Randomisation in blocks of variable size
(4, 6, and 8) was performed in an electronic case report
form system and stratified by site, age (≥60 years vs
<60 years), and respiratory status (use of oxygen at more
than 4 L/min, high-flow nasal cannula, non-invasive
positive-pressure ventilation, or mechanical ventilation).
Allocation was done by a centralised, web-based, automated randomisation system."
Comment: Allocation sequence random. Allocation sequence concealed. Baseline characteristics between intervention groups were comparable; any differences appear to be compatible with chance. |
| Deviations from intervention |
Some concerns |
Quote: "Patients, investigators,
and health-care providers were not masked to study drug
assignment."
Comment: Unblinded study.
4 patients in the intervention arm did not receive the assigned treatment and 2 in the control arm did not receive the assigned treatment and 7 received a macrolide during the study. Deviations in <10% of population No information on co-interventions of interest: antivirals, glucocorticoids, biologics and anticoagulants. |
| Missing outcome data |
Low |
Quote: "Two of the
447 patients were lost to follow-up (both after 15 days)
and one patient who did not have confirmed COVID-19
withdrew consent."
Comment: 447 patients randomized; 447 patients analyzed. Missingness due to documented reasons unrelated to the outcome. Risk assessed to be low for outcomes: Mortality. Time to death. Incidence of clinical improvement. Incidence of WHO score 6 and above. Incidence of WHO score 7 and above. Serious adverse events |
| Measurement of the outcome |
Some concerns |
Comment: Appropriate method of outcome measurement
Measurement of outcome does not differ between groups. Unblinded study Mortality is an obser-reported outcome not involving judgement. For the incidence of 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 outcomes: Mortality. Time to death. Incidence of WHO score 7 and above. Clinical improvement (defined as patients not hospitalized) and incidence of WHO score 6 and above reflects decisions made by the intervention provider. Furthermore. serious adverse events reported contain both clinically- and laboratory-detected events. Assessment of these outcomes could possibly be influenced by knowledge of the intervention assignment but we did not consider this likely to have happened in the context of a pandemic. Risk assessed to be some concerns for the outcomes: Incidence of clinical improvement. Incidence of WHO score 6 and above. Serious adverse events |
| Selection of the reported results |
Low |
Comment: The protocol and statistical analysis plan were available. Outcomes reported as prespecified.
Risk assessed to be low for the outcomes: Mortality. Time to death. Incidence of clinical improvement. Incidence of WHO score 6 and above. Incidence of WHO score 7 and above. Serious adverse events |
| Overall risk of bias |
Some concerns |