Neutrophil elastase inhibition in acute lung injury: Results of the STRIVE study
Neutrophil elastase inhibition in acute lung injury: Results of the STRIVE study
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DOI：
10.1097/01.ccm.0000133332.48386.85
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发表时间：
2004-08-01
影响因子：
8.8
通讯作者：
Bernard, G
中科院分区：
文献类型：
--
作者：
Zeiher, BG;Artigas, A;Bernard, G
目的：神经弹性蛋白酶被认为是急性肺损伤的重要介质。西维来司他（ONO-5046，Elaspol）是一种中性粒细胞弹性蛋白酶的小分子量抑制剂。本研究的主要目的是确定西维来司是否会降低28天全因死亡率或增加无呼吸机天数（从第1天到第28天无机械通气的存活天数）与安慰剂相比。设计：一项多中心、双盲、安慰剂对照试验，以0.16 mg剂量连续输注西维来司他（.）kg（-1.）hr（-1）.设置：美国、加拿大、比利时、西班牙、澳大利亚和新西兰的105家机构。患者：共492例急性肺损伤机械通气患者。患者以1：1的比例随机接受西维来司他或安慰剂治疗。研究药物在机械通气持续时间加24小时内连续输注给药，最长持续14天。所有患者均采用低潮气量机械ventilation.Measurements和主要结果：该研究被提前停止的建议，外部数据和安全监测委员会，指出长期死亡率的负趋势。最终分析显示西维来司对无呼吸机天数（第1天-第28天）或28天全因死亡率的主要终点无影响。在28天的研究期间，每个治疗组有64例死亡，西维来司和安慰剂治疗组的平均无呼吸机天数分别为11.4和11.9（p = 0.536）。没有证据表明对肺功能指标有影响，包括Pao（2）/Fi 0（2）、静态肺顺应性和达到撤机标准的时间。治疗组之间的不良事件或严重不良事件无差异。Kaplan-Meier 180天生存曲线的比较显示治疗组间无差异（p = 0.102），但西维来司治疗组的180天全因死亡率较安慰剂组增加（p = .006）.结论：静脉注射西维来司他对28天全因死亡率或呼吸机-采用低潮气量机械通气治疗的异质性急性肺损伤患者人群的无通气天数
Objective: Neutrophil elastase is believed to be an important mediator of acute lung injury. Sivelestat (ONO-5046, Elaspol) is a small molecular weight inhibitor of neutrophil elastase. The primary objectives of this study were to determine whether sivelestat would reduce 28-day all-cause mortality or increase the number of ventilator-free days (days alive and free from mechanical ventilation from day 1 to day 28) compared with placebo in mechanically ventilated patients with acute lung injury.Design: Multiple-center, double-blind, placebo-controlled trial administering a continuous infusion of sivelestat at a dose of 0.16 mg(.)kg(-1.)hr(-1).Setting: One hundred and five institutions in the United States, Canada, Belgium, Spain, Australia, and New Zealand.Patients: A total of 492 mechanically ventilated patients with acute lung injury.Interventions. Patients were randomized in a 1:1 fashion to sivelestat or placebo. Study drug was administered as a continuous infusion for the duration of mechanical ventilation plus 24 hrs for a maximum of 14 days. All patients were managed using low tidal volume mechanical ventilation.Measurements and Main Results: The study was stopped prematurely at the recommendation of an external Data and Safety Monitoring Board, which noted a negative trend in long-term mortality rate. Final analysis revealed no effect of sivelestat on the primary end points of ventilator-free days (day 1-day 28) or 28-day all-cause mortality. There were 64 deaths in each treatment group within the 28-day study period, and the mean number of ventilator-free days was 11.4 and 11.9 in the sivelestat and placebo treatment groups, respectively (p = .536). There was no evidence of effect on measures of pulmonary function, including Pao(2)/Fi0(2), static lung compliance, and time to meeting weaning criteria. There was no difference in adverse events or serious adverse events between treatment groups. A comparison of the Kaplan-Meier 180-day survival curves showed no difference between treatment groups (p = .102), but there was an increase in 180-day all-cause mortality in the sivelestat treatment group compared with the placebo group (p = .006).Conclusions: Intravenous sivelestat had no effect on 28-day all-cause mortality or ventilator-free days in a heterogeneous acute lung injury patient population managed with low tidal volume mechanical ventilation.