Early treatment with Drotrecogin alfa (activated) was associated with reduced hospital resource use in adult severe sepsis patients with two or more organ dysfunctions at baseline: results from ENHANCE

Background

In a phase 3 trial (PROWESS, n = 1690), 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, met three or four criteria defining systemic inflammatory response syndrome and one or more acute sepsis-induced (< 48 hour duration) organ dysfunctions. Days in the ICU, days in the hospital, and days of ventilator use were monitored, starting from time of DrotAA infusion. Patients were classified with respect to the time interval from the first documented organ dysfunction to administration of DrotAA in the intent-to-treat population with two or more organ dysfunctions at baseline that had received DrotAA within 24 hours after the first organ dysfunction (time 0–24 hours, n = 894) vs more than 24 hours after first organ dysfunction (time 24–48 hours, n = 1110).

Results

Table 1 describes patients with two or more organ dysfunctions at baseline. Administration of DrotAA within 24 hours of the first organ dysfunction was associated with reductions in days in the ICU, hospital length of stay, and mechanical ventilator use, relative to patients receiving DrotAA from 24–48 hours after first organ dysfunction.

Table 1 Table

Conclusion

Earlier treatment with DrotAA was associated with reduced hospital resource use and decreased length of stay in patients with two or more organ dysfunctions at baseline. These data suggest that the timely administration of DrotAA may have important clinical and economic value.