The international PROGRESS registry of patients with severe sepsis: drotrecogin alfa (activated) use and patient outcomes.

INTRODUCTION: Since the launch of drotrecogin alfa activated (DrotAA), institutions and individual countries have published data on its use in clinical practice, based on audit or registry data. These studies were limited in size and geographic locale and included patients with greater disease severity and higher mortality than those in clinical trials. The purpose of this study was to compare baseline characteristics and clinical outcomes (using appropriate statistical adjustments) of patients treated or not treated with DrotAA from the international PROGRESS (Promoting Global Research Excellence in Severe Sepsis) cohort study of severe sepsis.

METHODS: PROGRESS was a global, non-interventional, multi-center, prospective, observational study of patients having a diagnosis of severe sepsis treated in intensive care units at a participating institution. All treatment modalities were as per standard of care at the participating institutions. Baseline characteristics and hospital mortality were analyzed and regression techniques used to develop propensity and outcome models adjusted for baseline imbalances between groups.

RESULTS: Overall, 14,543 patients from 37 countries were enrolled and 12,492 had complete data for analysis. Germany was the highest enrolling country (1,810; 14.5%) and the US had the most DrotAA patients (206, 23.3%); 882 (7%) overall received DrotAA therapy. DrotAA-treated patients were younger (median age 58 vs. 61 years), had greater organ dysfunction (cardiovascular: 90% vs. 74%; respiratory: 90% vs. 81%; renal: 60% vs. 45%; metabolic: 63% versus 42%; 3 or more organ dysfunctions: 84% vs. 67%) and had a higher median APACHE II score (26 vs. 23, all with P < 0.001). Although in-hospital mortality was similar for DrotAA and non-DrotAA-treated patients (49.6% vs. 49.7%, respectively), after adjusting for imbalances, patients receiving DrotAA had a 28% (0.60 to 0.86, 95% Confidence Intervals) reduction in the odds of death and a relative risk reduction of 17% (P = 0.0003).

CONCLUSIONS: In the PROGRESS registry, DrotAA-treated patients were younger, more severely ill, and had fewer co-morbidities than patients not treated with DrotAA. After adjustment for group differences, a significant reduction in the odds of death was observed for patients that received DrotAA compared with those that did not.