| Bias | Author's judgement | Support for judgement |
| Randomization |
Some concerns |
Quote: “Enrolled subjects were randomized 1:1 to study drug or placebo and followed for 30 days. Randomization was stratified by age (>60 years old) and study site.”
Comment: Allocation sequence probably random. No information on allocation concealment. |
| Deviations from intervention |
Some concerns |
Quote: "Subjects and investigators were blinded to the treatment assignment, but in cases of rapid COVID-19 progression meeting our primary endpoint, or at the request of the treating physician, we allowed for subject unblinding."
Comment: Blinded study (patients and investigators), however, unblinding was allowed. No participant cross-over. Administration of co-interventions of interest: antivirals, corticosteroids and biologics were reported but it was unclear whether they were balanced between groups (no information). Considerable proportions of patients received cointerventions as part of other clinical trials. Data were analyzed using intention-to-treat analysis. |
| Missing outcome data |
High |
Comment: 128 patients randomized; 128 patients analyzed.
Viral negative conversion data for 61 patients, 47.7% missing. Reason: no follow-up PCR performed. Due to this and the equal proportion of missing data between the groups, there is evidence that the result was probably not biased. Risk assessed to be low for the outcome: Incidence of viral negative conversion. Mortality, Clinical improvement, WHO score 6 and above and WHO score 7 and above data for 11 patients (9%) missing on day 14. Mortality data for 25 patients (19.5%) missing on day 30. Adverse events data for 18 patients (14.1%) were missing. Reason given for missingness at day 30: lost to follow-up. No information on reason for missing adverse events data nor missing data for the other outcomes at day 14. Therefore, there is no evidence that the result was not biased, no information on whether missingness could depend on the true value of the outcome and no information on whether or not it was likely to. Risk assessed to be high for the outcomes: Mortality. Incidence of clinical improvement. WHO score 6 and above. WHO score 7 and above. Adverse events. |
| Measurement of the outcome |
Low |
Comment: Blinded study (outcome assessor). Risk assessed to be low for the outcomes: Mortality. Incidence of viral negative conversion. Incidence of clinical improvement. Incidence of WHO score 6 and above. Incidence of WHO score 7 and above. Adverse events. |
| Selection of the reported results |
Low |
Comment: Neither the protocol nor the statistical analysis plan was available. The registry would have been prospective "but due to administrative delays during COVID-19, the NYU Office of Science and Research submitted the registration to Clinicaltrials.gov on April 27, 2020." For the purpose of selective reporting and due to reasons given, we considered the data presented in the registry.
Result was not selected from multiple outcome measurements nor multiple analyses of the data. Trial was analyzed as pre-specified. Risk assessed to be low for the outcomes: Mortality. Incidence of viral negative conversion. Incidence of clinical improvement. WHO score 6 and above. WHO score 7 and above. Adverse events. |
| Overall risk of bias |
High |