Experience from clinical practice may differ from clinical trials both in patient (pt) selection and outcomes. Xigris Evaluation in the United States (XEUS) is a prospective observational study of drotrecogin alfa (activated) (DrotAA) use in clinical practice. This is a report on the safety of DrotAA in XEUS.
Between April 2003 and March 2004, data were prospectively collected from a convenience sample of pts receiving DrotAA at 61 acute care hospitals in the United States. Data included: baseline characteristics, platelet count, recent surgery (RS), and serious bleeding events (SBE). Bleeding was an SBE if it was (1) life threatening; (2) intracranial hemorrhage (ICH); or (3) required transfusion of 3 units of RBCs/day for 2 consecutive days. Pts were followed until hospital discharge or up to 28 inpatient days, whichever came first (HD-28).
484 records were available for review. There were 16 SBEs (3.3%, 95% CI 1.9-5.8) with one ICH (0.2%). These results were similar to the 28-day SBE rate (3.5%) and ICH rate (0.2%) for DrotAA pts in PROWESS. SBEs occurred in 4.7% (CI 2.0 –9.1) of pts with RS and in 2.5% (CI 1.1-5.2) of non-surgical pts. The number of SBEs in RS pts was small (N=8), and there was no apparent association between the time of RS (<24 hours, 24-72 hours, 4-7 days, 8-30 days) and the rate of SBE (3.8%, 6.4%, 2.9%, 3.2%, respectively)(p= 0.8508). Almost one quarter (N=118) of pts had chronic liver disease, active cancer, or a platelet count < 30,000; these groups were underrepresented in PROWESS. 3.4% of these pts had SBE.
The incidence of SBE in XEUS was similar to PROWESS. The timing of RS had no apparent association with the rate of SBE. In XEUS, pts that would have been excluded from PROWESS had an SBE rate similar to other patients.
The safety profile of DrotAA in clinical practice appears to be similar to that documented in randomized clinical trials (PROWESS).
J. Steingrub, None.