Reevaluation of the efficacy and safety of the neutrophil elastase inhibitor, Sivelestat, for the treatment of acute lung injury associated with systemic inflammatory response syndrome; a phase IV study
Reevaluation of the efficacy and safety of the neutrophil elastase inhibitor, Sivelestat, for the treatment of acute lung injury associated with systemic inflammatory response syndrome; a phase IV study
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DOI：
10.1016/j.pupt.2011.03.001
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发表时间：
2011-10-01
影响因子：
3.2
通讯作者：
Kawasaki, Yasushi
中科院分区：
文献类型：
--
作者：
Aikawa, Naoki;Ishizaka, Akitoshi;Kawasaki, Yasushi
Sivelestat是一种中性粒细胞弹性酶抑制剂，已在日本被批准用于治疗急性肺损伤（ALI）合并全身炎症反应综合征（SIRS）患者。药品和医疗器械管理局（PMDA）已下令进行上市后临床研究，以便在日本的实际临床环境中重新评估Sivelestat的有效性和安全性。方法：根据PMDA的指令，我们以无呼吸机天数（VFD）为主要终点，评估西维司他在日本ALI合并SIRS患者中的疗效和安全性。替代终点为呼吸机脱机率、ICU出院率和180天生存率。研究设计为开放标签、非随机、多中心临床试验。西维司他以0.2 mg/kg/h静脉滴注，连续最多14天。采用基于倾向评分的治疗逆概率加权法调整转归值，比较西韦司他组和对照组。结果：纳入西韦司他组患者404例，对照组患者177例。西维司他组和对照组调整后的平均VFD数分别为15.7个和12.1个（P=0.0022）。西维司他组调整后的呼吸机脱机率和ICU出院率均显著高于对照组（P=0.0028和P=0.019）。Sivelestat组调整后的180天生存率明显高于对照组（71.8% vs. 56.3%）。结论：西维司他有助于机械通气的早期脱机，而对SIRS相关的ALI的长期结局没有负面影响。本研究的结果表明西韦司他在该患者群体中的临床应用价值。(C) 2011 Elsevier Ltd.版权所有。
Introduction: Sivelestat, a neutrophil elastase inhibitor, has been approved in Japan for the treatment of patients with acute lung injury (ALI) associated with systemic inflammatory response syndrome (SIRS). The Pharmaceuticals and Medical Devices Agency (PMDA) has ordered to conduct a postmarket clinical study in order to reevaluate the efficacy and safety of Sivelestat in actual clinical settings in Japan.Methods: According to the PMDA's order, we evaluated the efficacy and safety of Sivelestat in Japanese patients with ALI associated with SIRS using ventilator-free days (VFD) as the primary endpoint. The surrogate endpoints are ventilator-weaning rate, ICU discharge rate, and 180-day survival rate. Study design was an open-label, non-randomized, multi-center clinical trial. Sivelestat was intravenously administered at 0.2 mg/kg/h continuously for a maximum of 14 days. Sivelestat group and control group were compared by adjusting the outcome values using an inverse probability of treatment weighted method based on the propensity scores.Results: Four hundred and four Sivelestat group patients and 177 control group patients were enrolled. The adjusted mean number of VFD was 15.7 and 12.1 in the Sivelestat group and control group, respectively (P=0.0022). Both the adjusted ventilator-weaning rate and ICU discharge rate were significantly higher in the Sivelestat group than in the control group (P=0.0028 and P=0.019, respectively). The adjusted 180-day survival rate was significantly higher in the Sivelestat group than in the control group (71.8 percent vs. 56.3 percent).Conclusions: Sivelestat contributed to early weaning from the mechanical ventilation, while showing no negative effect on the long-term outcomes of ALI associated with SIRS. The results of this study suggest the clinical usefulness of Sivelestat in this patient population. (C) 2011 Elsevier Ltd. All rights reserved.