Early treatment with Drotrecogin alfa (activated) was associated with reduced hospital resource use in adult severe sepsis patients with an APACHE II score of 25 or greater at baseline: results from ENHANCE

Background

In a phase 3 clinical trial (PROWESS, n = 1690 patients), Drotrecogin alfa (activated) (DrotAA) was associated with a significant survival improvement and favorable benefit–risk profile compared with placebo in adult patients with severe sepsis receiving standard supportive care. A global, single-arm, open-label trial of DrotAA in adult patients with severe sepsis (ENHANCE, n = 2378) was subsequently conducted at 361 sites in 25 countries, and hospital resource usage was assessed with respect to the timing of DrotAA administration.

Methods

Inclusion and exclusion criteria were similar to PROWESS. Patients eligible for participation had a known or suspected infection, three or four of the criteria defining the systemic inflammatory response syndrome, and one or more acute sepsis-induced (< 48 hour duration) organ dysfunctions. Days in the ICU, days in the hospital, days of ventilator use, and days of vasopressor use were monitored, starting from the time of DrotAA infusion. Patients were subclassified with respect to the time interval from the first documented organ dysfunction to administration of DrotAA (time-to-treatment). Time-to-treatment was considered in the intent-to-treat population with an APACHE II score of 25 or more at baseline that had received DrotAA within 24 hours of the first organ dysfunction (n = 430) vs those that received the drug more than 24 hours after first organ dysfunction (n = 432).

Results

Data presented are from severe sepsis patients with an APACHE II score of 25 or more at baseline. The administration of DrotAA within 24 hours of the first observed organ dysfunction was associated with significant reductions in days in the ICU (median ICU days = 10 for time: 0–24 hours, 14 for time: 24–48 hours; P = 0.006), mechanical ventilator use (median ventilator days = 7 for time: 0–24 hours, 10 for time: 24–48 hours; P < 0.001), and vasopressor use (median vasopressor days = 2 for time: 0–24 hours, 3 for time: 24–48 hours; P = 0.003), relative to patients receiving DrotAA after more than 24 hours from first organ dysfunction. Median days in the hospital were lower in patients receiving DrotAA within 24 hours of first organ dysfunction, but the difference was not statistically significant (median hospital days = 18.5 for time: 0–24 hours, 22 for time: 24–48 hours; P = 0.103).

Conclusion

Earlier treatment with DrotAA was associated with reduced hospital resource use in patients with an APACHE II score of 25 or more at baseline. These data suggest that the timely administration of DrotAA may have important clinical and economic value.