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Severe sepsis and drotrecogin alfa (activated) use: results from the PROGRESS registry


Since the launch of drotrecogin alfa (activated) (DAA) a number of institutions and countries have published data on its use in clinical practice, based on audit or registry data. Such publications have tended to report DAA use in higher disease severity populations together with higher mortality outcomes compared with clinical trials. We utilized the Global PROGRESS (Promoting Global Research Excellence in Severe Sepsis) database to examine the baseline characteristics and outcome of patients with and without DAA treatment.


PROGRESS is a global, noninterventional, multicenter, prospective, observational study of severe sepsis patients treated in ICUs. Patients must have had a diagnosis of severe sepsis and have been treated in an ICU at a participating institution. All treatment modalities were as per standard of care at the participating institutions. We analyzed baseline characteristics and hospital mortality. We also performed an adjusted mortality analysis for DAA patients due to baseline imbalances in patients with and without DAA therapy.


Overall, 12,492 patients with severe sepsis from 37 countries were enrolled and 882 (7%) patients received DAA therapy. The highest rate of use of DAA was seen in the United States at 27% (206/760). Patients who received DAA versus those who did not receive DAA were younger (median age 59 versus 64 years), had greater organ dysfunction (cardiovascular dysfunction (90% versus 74%), respiratory dysfunction (90% versus 81%), renal dysfunction (60% versus 45%), metabolic abnormalities (63% versus 42%), three or more organ dysfunctions (84% versus 67%)) and higher median APACHE II scores (25.0 vs 23.0), all P < 0.001. The mortality rate for patients treated with DAA was 49.6% and for those not treated with DAA was 49.7%. Although imbalances in other baseline characteristics, not collected in PROGRESS, may have also been present, when adjusted for age and number of organ dysfunctions the odds ratio for hospital mortality associated with DAA use was 0.75 (0.63–0.90, P = 0.002).


In a large global registry, patients receiving DAA therapy were younger with higher disease severity than patients not treated with DAA. When adjusted for age and number of organ dysfunctions, DAA was associated with a reduction in the odds of hospital mortality similar to that seen at day 28 in PROWESS. These data are supportive of the effectiveness of DAA in clinical practice.

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Correspondence to R Beale or F Brunkhorst or G Martin or M Williams or D Nelson or J Janes.

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Beale, R., Brunkhorst, F., Martin, G. et al. Severe sepsis and drotrecogin alfa (activated) use: results from the PROGRESS registry. Crit Care 11, P64 (2007).

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  • Severe Sepsis
  • Organ Dysfunction
  • Hospital Mortality
  • Sepsis Patient
  • Drotrecogin Alfa