2.8. Definition of Endpoints
death
ADVERSE EVENTS, EVENTS, EVENT, SECONDARY
The primary endpoints were evaluated in the intention-to-treat (ITT) population to assess the effect of oral bovine lactoferrin in modifying at least one of the following: (1) a decrease in the proportion of a composite event rate consisting of one of two events, whichever occurred first: hospitalization in ICU (due to any cause) or in-hospital death, and (2) an increase in the proportion of a composite event rate consisting of one of two events, whichever occurred first: discharge from hospital within 14 days from enrollment or a National Early Warning Score 2 (NEWS2) ≤ 2 for at least 24 h within 14 days from enrollment. The secondary endpoints were defined as differences in outcomes between the treatment and the placebo groups as follows: (i) variations, either improvements or worsening, in the NEWS2 score from baseline values to those measured at 7, 14, and 21 days; (ii) the need for oxygen supplementation and, if so, its duration; (iii) the need for non-invasive ventilation (NIV), including a high-flow nasal cannula (HFNC) and a properly defined NIV, encompassing either continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BiPAP) using a non-invasive interface; (iv) the need for invasive mechanical ventilation; (v) variations in in-hospital mortality rates at 14 and 28 days from enrollment; (vi) variations in C-reactive protein (CRP), interleukin 6 (IL-6), and ferritin plasma levels during hospitalization; and (vii) adverse events related to the treatments. The primary endpoints were also evaluated in two different age subgroups (<65 years vs. ≥65 years) and in relation to gender.