|Bias||Author's judgement||Support for judgement|
|Quote: "Randomisation was performed in an electronic case report form system (RedCap Database), 1:1 with random block sizes of 4, 6, or 8 subjects using tables generated from STATA (v16·1)"
Comment: Allocation sequence random. No information on allocation concealment.
|Deviations from intervention||
|Quote: “Open label”
"Patients, investigators, and health-care providers were not masked to study drug assignment."
Comment: Unblinded study.
9 control patients were treated with progesterone due to clinical deterioration prior to Day 7 (n = 6, 27%) or absence of clinical improvement by Day 7 (n = 3, 14%). No information on whether this deviation was consistent with the trial protocol since the protocol was not available.
Administration of co-interventions of interest (antivirals, biologics, and corticosteroids) were reported. Slightly more patients in the control group received antivirals and corticosteroids (9/18 vs 15/22) and biologics (Tocilizumab: 1/18 vs 4/22; Convalescent plasma: 0/18 vs 2/22). Hence there were deviations that arose because of the trial context but they were not considered to have affected the outcome.
Data were analyzed using intention-to-treat analysis. The participants in the control group that received progesterone were analyzed with imputation (last observation carried forward) in the group they were randomized to.
|Missing outcome data||
|Comment: 42 patients randomized; 40 patients analyzed.
Data available for > 95% of population.
Risk assessed to be low for the outcomes : Mortality. WHO score 6 and above. WHO score 7 and above. Serious adverse events.
|Measurement of the outcome||
|Comment: Appropriate method of measuring the outcomes.
Measurement or ascertainment of outcomes do not differ between groups.
Mortality is an observer-reported outcome not involving judgement. For WHO score 7 and above, we consider that the assessment cannot possibly be influenced by knowledge of intervention assignment.
WHO score 6 and above requires clinical judgement and could be affected by knowledge of intervention receipt, but is not likely in the context of the pandemic.
Risk assessed to be some concerns for the outcome: WHO score 6 and above.
|Selection of the reported results||
|Comment: The trial registry was available. The protocol and statistical analysis plan were not.
Results for COVID-19 clinical severity scores were pre-specified as reported.
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: WHO score 6 and above. WHO score 7 and above.
Mortality at day 7 (as part of the Change in clinical status outcome) was pre-specified as reported but for day 15, the outcome was listed in the registry as being "on Day 15 [Time Frame: 29 days]", hence, conflicting information. Furthermore, adverse events and serious adverse events were not pre-specified in the registry. The trial only reported on Grade 3 and 4 non-serious adverse events and serious adverse events without a definition.
No information on whether the results for mortality, adverse events and serious adverse events were selected from multiple outcome measurements or analyses of the data.
Trial not analyzed as pre-specified.
Risk assessed to be some concerns for the outcomes: Mortality. Serious adverse events.
|Overall risk of bias||