Randomized trial of zileuton for treatment of COPD exacerbations requiring hospitalization.
Randomized trial of zileuton for treatment of COPD exacerbations requiring hospitalization.
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DOI：
10.3109/15412555.2010.540273
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发表时间：
2011-02
期刊：
影响因子：
2.2
通讯作者：
Copd Clinical Research Network
中科院分区：
文献类型：
--
作者：
Woodruff PG;Albert RK;Bailey WC;Casaburi R;Connett JE;Cooper JA Jr;Criner GJ;Curtis JL;Dransfield MT;Han MK;Harnden SM;Kim V;Marchetti N;Martinez FJ;McEvoy CE;Niewoehner DE;Reilly JJ;Rice K;Scanlon PD;Scharf SM;Sciurba FC;Washko GR;Lazarus SC;Copd Clinical Research Network
白三烯与COPD急性加重的发病机制有关，但尚未研究过将白三烯调节剂作为急性加重的可能治疗方法。我们试图测试在常规治疗中加入口服齐留通（一种5-脂氧合酶抑制剂）治疗需要住院的COPD急性加重的安全性和有效性。一项随机、双盲、安慰剂对照、平行组研究，比较齐留通600 mg口服，每日4次与安慰剂，在因COPD急性加重入院后12小时内开始，持续14天。主要结局指标为住院时间;次要结局指标包括治疗失败和白三烯产生的生物标志物。60名受试者被随机分配到zileuton组，59名被随机分配到安慰剂组（由于招募缓慢，该研究未达到招募目标而停止）。住院时间无差异（齐留通vs.安慰剂为3.75±2.19 vs. 3.86±3.06天，p=0.39）或治疗失败（齐留通与安慰剂的23%对27%，p=0.63），尽管与安慰剂组相比，齐留通治疗组24小时尿LTE 4水平下降（自然对数转换的ng/mg肌酐变化−1.38± 1.19 vs. 0.14±1.51，p<0.0001）和72小时（−1.32±2.08 vs. 0.26±1.93，p<0.006）。两组的不良事件相似。虽然在需要住院的COPD急性加重期间口服齐留通是安全的，并可降低尿LTE 4水平，但我们没有发现证据表明这种干预缩短了住院时间，限制是我们的样本量可能不足以检测到适度但可能有意义的临床改善。
Leukotrienes have been implicated in the pathogenesis of acute exacerbations of COPD, but leukotriene modifiers have not been studied as a possible therapy for exacerbations. We sought to test the safety and efficacy of adding oral zileuton (a 5-lipoxygenase inhibitor) to usual treatment for acute exacerbations of COPD requiring hospitalization. Randomized double-blind, placebo-controlled, parallel group study of zileuton 600 mg orally, 4 times daily versus placebo for 14 days starting within 12 hours of hospital admission for COPD exacerbation. Primary outcome measure was hospital length of stay; secondary outcomes included treatment failure and biomarkers of leukotriene production. Sixty subjects were randomized to zileuton and 59 to placebo (the study was stopped short of enrollment goals because of slow recruitment). There was no difference in hospital length of stay (3.75±2.19 vs. 3.86±3.06 days for zileuton vs. placebo, p=0.39) or treatment failure (23% vs. 27% for zileuton vs. placebo, p=0.63) despite a decline in urinary LTE4 levels in the zileuton-treated group as compared to placebo at 24 hours (change in natural log-transformed ng/mg creatinine −1.38± 1.19 vs. 0.14±1.51, p<0.0001) and 72 hours (−1.32±2.08 vs. 0.26±1.93, p<0.006). Adverse events were similar in both groups. While oral zileuton during COPD exacerbations that require hospital admission is safe and reduces urinary LTE4 levels, we found no evidence suggesting that this intervention shortened hospital stay, with the limitation that our sample size may have been insufficient to detect a modest but potentially meaningful clinical improvement.
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