Treatment with drotrecogin alfa (activated) [DrotAA] and standard supportive care in a phase 3 clinical trial conducted at 164 sites in 11 countries was found to be associated with a significant mortality reduction and favorable benefit-risk profile compared to placebo and standard supportive care in adult patients with severe sepsis (PROWESS; DrotAA n = 850; placebo n = 840). We now report baseline characteristics and mortality from a global, single-arm, open-label trial of DrotAA in adult patients with severe sepsis conducted at 400 sites in 25 countries (ENHANCE, n=2378).
Inclusion and exclusion criteria were virtually identical to PROWESS. All-cause mortality was assessed at study day 28. Patients eligible for participation had known or suspected infection, 3 or 4 of the criteria defining the systemic inflammatory response syndrome, and 1 or more acute (<48 hr duration) organ dysfunctions. Patients at high risk for bleeding were excluded from participation.
VariableENHANCE (DrotAA) (N = 2378)PROWESS (DrotAA) (n = 850)PROWESS (Placebo) (n = 840)Baseline CharacteristicsAge (years; mean (SD))59 (17)60 (17)61(16)Males (%)585658APACHE II (mean (SD))22.0 (7.4)24.6 (7.6)25.0 (7.8)Acute Physiology Score (mean (SD))18.6 (7.1)20.2 (7.1)20.5 (7.1)Organ Dysfunctions (mean (SD))2.7 (1.1)2.4 (1.1)2.4 (1.1)≥2 Organ Dysfunctions (%)84.374.675.9≥3 Organ Dysfunctions (%)54.642.843.4Ventilator Support (%)82.073.377.6Vasopressor Support (%)73.771.875.528-Day MortalityOverall (%)25.324.730.8Only countries in both studies* (%)23.4 (n=1478)24.7 (n=814)31.7 (n=805)*
Results for countries in common to both ENHANCE and PROWESSCONCLUSIONS: DrotAA patients in ENHANCE tended to have lower APACHE scores but more organ dysfunctions at baseline compared with placebo patients in PROWESS. Overall mortality was similar for DrotAA-treated patients in ENHANCE and PROWESS and lower than for patients receiving placebo. These data indicate that the treatment effect associated with DrotAA remains robust despite the increase in number of countries and investigative sites participating in clinical studies.
An increase in survival can be expected with the use of drotrecogin alfa (activated) in adult patients with severe sepsis.
A.P. Wheeler, None. Eli Lilly and Company (Indianapolis, IN) provided support for this research.