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Crit Care Med. 2005 Oct;33(10):2266-77.

Drotrecogin alfa (activated) treatment in severe sepsis from the global open-label trial ENHANCE: further evidence for survival and safety and implications for early treatment.

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1
Department of Intensive Care, Erasme University Hospital and University of Brussels, Brussels, Belgium.

Abstract

OBJECTIVE:

To provide further evidence for the efficacy and safety of drotrecogin alfa (activated) treatment in severe sepsis.

DESIGN:

Single-arm, open-label, trial of drotrecogin alfa (activated) treatment in severe sepsis patients. Enrollment began in March 2001 and day-28 follow-up completed in January 2003.

SETTING:

ENHANCE took place in 25 countries at 361 sites.

PATIENTS:

Patients with known or suspected infection, three or four systemic inflammatory response syndrome criteria, and one or more sepsis-induced organ dysfunctions. Of 2,434 adults entered, 2,378 received drotrecogin alfa (activated), and of these, 2,375 completed the protocol.

INTERVENTIONS:

Drotrecogin alfa (activated) was infused at a dose of 24 mug/kg/hr for 96 hrs.

MEASUREMENTS AND MAIN RESULTS:

The 28-day all-cause mortality approximated that observed in PROWESS (25.3% vs. 24.7%). Although patients in ENHANCE had increased serious bleeding rates compared with patients in the drotrecogin alfa (activated) arm of PROWESS (during infusion, 3.6% vs. 2.4%; postinfusion, 3.2% vs. 1.2%; 28-day, 6.5% vs. 3.5%), increased postinfusion bleeding suggested a higher background bleeding rate. Intracranial hemorrhage was more common in ENHANCE than PROWESS (during infusion, 0.6% vs. 0.2%; 28-day, 1.5% vs. 0.2%). The incidence of fatal intracranial hemorrhage was the same during infusion (0.2%) and higher at 28 days (0.5% vs. 0.2%). ENHANCE patients treated within 0-24 hrs from their first sepsis-induced organ dysfunction had lower observed mortality rate than those treated after 24 hrs (22.9% vs. 27.4%, p = .01).

CONCLUSIONS:

ENHANCE provides supportive evidence for the favorable benefit/risk ratio observed in PROWESS and suggests that more effective use of drotrecogin alfa (activated) might be obtained by initiating therapy earlier.

PMID:
16215381
[Indexed for MEDLINE]
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