Statistical Analysis
REGRESSION, SECONDARY
Data analysis was performed from April to October 2021. Assuming a confidence level of 0.95, a 2-sided test, and a proportion of 78% of patients not requiring mechanical ventilation in the SoC group, an effective sample size of 90 patients per group (180 patients in total) was required to provide 0.75 power in detecting as significantly different a proportion of 92% of patients not requiring it in the anakinra group. The assumed proportion in the SoC group (78%) was based on an estimation using available data from participating hospitals, and the target difference (14%) was chosen trying to have a trade-off between clinical relevance and feasibility. Analyses of the primary and secondary outcomes and the safety analysis were performed on an intention-to-treat (ITT) basis. Exploratory outcomes were assessed for all patients who had available follow-up data at each time point. No data imputation was done to account for missing data, which accounted for only 5% of the data.The treatment effect size for the primary and secondary end points was measured on the basis of the relative risk ratio (RR). The treatment effect was also expressed using the hazard ratio (HR) with the 95% CI for time to mechanical ventilation and mortality, plotted with Kaplan-Meier survival curves and compared with the log-rank test. Post hoc adjusted Cox regression analyses were performed and included COVID-19 severity (World Health Organization clinical progression scale score >5 vs ≤5) and use of dexamethasone as an important prognostic factor based on the RECOVERY study.