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Friday, September 04, 2009

Xigris and more...

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

Greg Martin1 , Frank M Brunkhorst2 , Jonathan M Janes3 , Konrad Reinhart2 , David P Sundin3 , Kassandra Garnett4 and Richard Beale5

1Division of Pulmonary, Allergy, and Critical Care, Emory University, 615 Michael Street, Atlanta, Georgia, 30322, USA

2Department of Anesthesiology and Intensive Care, Friedrich Schiller University, Erlanger Allee 101, Jena, 07743, Germany

3Lilly Research Laboratories, Eli Lilly and Co., Lilly Corporate Center, Indianapolis, Indiana, 46285, USA

4 StatProbe, 1001 Winstead Drive, Cary, North Carolina, 27513, USA

5Intensive Care Unit, Guy's and St Thomas' Hospital, Lambeth Palace Road, London, SE1 7EH, UK




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 <>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.