Canadian ENHANCE data support the efficacy and safety of drotrecogin alfa (activated) despite higher disease severity than the global ENHANCE population

Abstract

The ENHANCE trial was an open-label, multi-national (25 countries) study of drotrecogin alfa (activated) (DrotAA) in 2378 patients with severe sepsis (systemic inflammatory response due to acute infection and ≥ 1 sepsis-induced organ dysfunction of ≤ 48 hours duration). In Canada, 305 patients were enrolled at 18 sites. DrotAA was infused for 96 hours at 24 mg/kg/hour. Patients continued to receive supportive care. Table 1 presents baseline characteristics, bleeding events, and 28-day all-cause mortality for Canadian and Global ENHANCE populations. Canadian patients demonstrated higher disease severity at baseline by organ dysfunction and APACHE II, yet had numerically lower mortality and fewer infusion period serious bleeds than the Global ENHANCE overall population. Comparison of laboratory and severity variables between survivors and non-survivors using the Wilcoxon two-sample test suggests that possible predictors of survival in Canadian ENHANCE patients were: first day change in creatinine; number of organ failures at baseline; pre-infusion APACHE II score; and enrollment at PROWESS study sites. In conclusion, differences were observed in disease severity and outcomes in Canadian ENHANCE patients compared with the overall trial sample. Table 1 Baseline characteristics and outcomes Canadian ENHANCE (n = 305) Global ENHANCE (n = 2378) Mean age, years (SD) 56.9 (17.2) 59.1 (16.9) APACHE II ICU (SD) 25.3 (7.8) 22.0 (7.4) # Organ failure (SD) 3.1 (1.2) 2.7 (1.1) Baseline SOFA (SD) 10.9 (3.6) 9.7 (3.5) Vasopressor use (%) 82% 74% Mechanical ventilation (%) 90% 82% Infusion serious bleed (%) 2.0% 3.6% 28-Day serious bleed (%) 3.9% 6.5% Infusion ICH (%) 0.3% 0.6% 28-Day mortality (%) 22.6% 25.3% SD, standard deviation.