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.
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Tags
- Administration
- Adult,
- Aged,
- Agents,
- C,
- Drug
- Female,
- Hemorrhages,
- Humans,
- Intracranial
- Male,
- Middle
- Outcome
- Protein
- Proteins,
- Rate,
- Recombinant
- Schedule,
- Sepsis,
- Studies,
- Survival
- Treatment
- {Anti-Infective}
- {Follow-Up}