Rotrecogin alfa (activated) [DrotAA] significantly reduced mortality and improved organ function in severe sepsis patients (PROWESS Study; n=1690). We now report sequential organ failure assessment (SOFA) scores from 2378 patients enrolled in a global, single-arm, open-label trial of DrotAA in adult patients with severe sepsis (ENHANCE Study).
Inclusion and exclusion criteria were virtually identical to PROWESS. 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. Organ function was assessed daily using a modified SOFA score. Time-averaged SOFA scores for Days 1–28, adjusted for imbalances in SOFA scores at baseline, are reported.
VariableENHANCE (DrotAA) [n = 2378]PROWESS (DrotAA) [n = 850]PROWESS (Placebo) [n = 840]SOFA scores at baseline (mean (SEM))Cardiovascular3.01 (0.03)2.61 (0.05)2.69 (0.05)*Respiratory2.73 (0.02)2.65 (0.04)2.70 (0.04)Hepatic0.65 (0.02)0.60 (0.03)0.58 (0.03)Renal1.26 (0.02)1.12 (0.04)1.11 (0.04)*Hematologic0.83 (0.02)0.70 (0.03)0.67 (0.03)*28-day time-averaged SOFA scores (mean (SEM))Cardiovascular1.40 (0.03)1.36 (0.05)1.52 (0.05)*Respiratory2.18 (0.02)2.12 (0.04)2.23 (0.04)Hepatic1.04 (0.03)1.05 (0.05)1.19 (0.05)*Renal1.17 (0.03)1.18 (0.04)1.31 (0.05)*Hematologic1.00 (0.03)1.03 (0.05)1.18 (0.05)*
SEM = standard error of the mean,*
= P < 0.05 ENHANCE DrotAA vs. PROWESS PlaceboCONCLUSIONS: Patients in ENHANCE had worse organ dysfunction at baseline compared with placebo patients in PROWESS. Despite the imbalance at baseline, administration of DrotAA was associated with statistically significantly lower time averaged cardiovascular, hepatic, renal and hematologic scores consistent with greater improvement in organ function compared with placebo treated patients.
The results of the ENHANCE study confirm the observation in PROWESS that administration of DrotAA is associated with significant improvement in organ function.
J. Vincent, None. Eli Lilly and Company (Indianapolis, IN) provided support for this research.