Bertolini Guido, Rossi Carlotta, Anghileri Abramo, Livigni Sergio, Addis Antonio, Poole Daniele
Laboratory of Clinical Epidemiology, GiViTi Coordinating Center, Istituto di Ricerche Farmacologiche "Mario Negri", Centro di Ricerche Cliniche per le Malattie Rare Aldo e Cele Daccò, Villa Camozzi, 24020, Ranica (Bergamo), Italy.
Intensive Care Med. 2007 Mar;33(3):426-34. doi: 10.1007/s00134-007-0554-x. Epub 2007 Feb 15.
To monitor the use of drotrecogin alfa activated (DrotAA) in Italy and its effects on patients' health.
Prospective pharmaco-surveillance program with a parallel non-randomized control group.
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.
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.
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.
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.
监测意大利活化蛋白C（DrotAA）的使用情况及其对患者健康的影响。
采用平行非随机对照组的前瞻性药物监测项目。
卫生部要求所有使用DrotAA的重症监护病房（ICU）参与该药物监测项目。我们的对照组由符合DrotAA治疗条件但未接受该治疗的患者组成。
我们收集的数据包括基本人口统计学特征、适应证、使用方式、不良事件和ICU死亡率。我们根据医院购买DrotAA的数据确定了可能不合作的中心。
2003年至2006年，共报告了668例DrotAA治疗病例。我们估计这一时期意大利所有接受治疗的患者中有79.3%被纳入研究。超说明书用药很常见。开始用药延迟是超说明书处方的主要原因。73例患者（10.9%）在输注过程中出现出血。出血患者的ICU死亡率更高（57.5%对44.9%；p=0.041）。接受DrotAA治疗的患者的ICU粗死亡率低于对照组（46.4%对54.9%；p=0.0004）；然而，在对某些相关差异进行调整的多因素分析中，显示DrotAA治疗与择期手术后较高的死亡率相关。
这些结果对该药物在日常临床实践中的使用方式及其在特定亚组中的疗效提出了质疑，并强化了进行一项新的、独立的验证性试验以重新评估DrotAA风险效益比的必要性。
