Objective: To monitor the use of drotrecogin alfa activated (DrotAA) in Italy and its effects on patients' health.
Design: Prospective pharmaco-surveillance program with a parallel non-randomized control group.
Setting: The Ministry of Health required all intensive care units (ICUs) using DrotAA to participate in the pharmaco-surveillance program. Our control group was formed of patients eligible for treatment with DrotAA but who had not received it.
Patients and participants: The data we collected included basic demographic characteristics, indications, modalities of use, adverse events, and ICU mortality. We identified potentially non-collaborating centres on the basis of data on DrotAA purchasing by hospitals.
Measurements and results: From 2003 to 2006, 668 cases of treatment with DrotAA were reported. We estimate that 79.3% of all patients treated in Italy in this period were recruited. Off-label use was common. Delayed start was the main reason for off-label prescription. Bleeding during infusion occurred in 73 patients (10.9%). The ICU mortality was higher in patients with bleeding (57.5 vs. 44.9%; p=0.041). Crude ICU mortality was lower in patients receiving DrotAA than in controls (46.4 vs. 54.9%; p=0.0004); however, multivariate analysis, which adjusted for certain relevant differences, showed that DrotAA treatment was associated with higher mortality after scheduled surgery.
Conclusions: These results question the way in which the drug is used in everyday clinical practice and its efficacy in a selected subgroup, and reinforce the need for a new, independent, confirmatory trial to reassess the risk-to-benefit ratio of DrotAA.