长效β2受体激动剂维兰特罗治疗持续性哮喘的疗效和最佳给药间隔：随机临床试验
2012/07/06
摘要
背景：维兰特罗（VI）是一个新的长效β2受体激动剂，每天仅需给药1次，药效能持续24 h。本试验旨在评价VI每天1次、连续3天给药和每天两次、1天给药，联合ICS在治疗成人（≥18岁）持续哮喘中的疗效。同时评价治疗的安全性。
方法：本试验为多中心、随机、双盲、安慰剂-对照、5年期交叉临床研究，由7天治疗期间隔7天洗脱期组成。75名采用ICS维持治疗的患者入选，接受VI 6.25、12.5和25 mcg每天1次（晚上）、VI 6.25 mcg每天2次（早上/晚上）及安慰剂治疗。主要终点为第7天时的第1秒用力呼气体积（FEV1）最低值（晚上用药后23 h和24 h平均值）；次要终点为第7天时一系列FEV1的加权平均值。
结果：与安慰组相比，所有VI治疗组的FEV1最低值均显著增加（P< 0.001）。与安慰剂组相比，各VI组的24-h FEV1加权平均值显著增加（P< 0.001）。每日1次VI治疗对FEV1最低值和24-h FEV1加权平均值的影响呈现剂量依赖性。各VI治疗组，副作用的发生率很低，也非剂量依赖性（5-9%；安慰剂= 18%）。未见非药物相关副作用或严重副作用。
结论：每日1次VI治疗能很好耐受，能改善肺功能。VI 6.25 mcg每日2次对FEV1最低值的影响最大，但VI 12.5 mcg每日1次治疗对24-h FEV1加权平均值影响最大。虽然我们研究并未证实每日1次和每日2次VI治疗的非劣效性，但数据显示，在总剂量一定的情况下，每日2次VI治疗与每日1次治疗相比，并未显示其优势。临床试验注册号：NCT00980200。
（刘国梁 审校）
Respir Med. 2012 Apr 18. [Epub ahead of print]
Respir Med. 2012 Apr 18. [Epub ahead of print]
Source
Carolina Research, Respiratory Medicine, Orangeburg, SC 29118-2040, USA.
Abstract
BACKGROUND: Vilanterol (VI) is a novel once-daily long-acting beta(2) agonist with inherent 24-h activity. The aim of this study was to evaluate the efficacy of three once-daily doses and one twice-daily dose of VI used concurrently with ICS in adult patients (≥18 years) with persistent asthma. Safety was also assessed.
METHODS: Multicentre, randomised, double-blind, placebo-controlled, five-period crossover study consisting of 7-day treatment periods separated by 7-day wash-out periods. Seventy-five patients, maintained on ICS, received VI 6.25, 12.5 and 25 mcg once-daily (evening), VI 6.25 mcg twice-daily (morning/evening), and placebo. The primary endpoint was trough forced expiratory volume in 1 s (FEV(1)) (mean of 23 h and 24 h post evening dose) on Day 7; secondary endpoint was weighted mean 24-h serial FEV(1) on Day 7.
RESULTS: All VI groups demonstrated statistically significant increases in trough FEV(1) versus placebo (p < 0.001). There was a statistically significant increase in weighted mean 24-h FEV(1) for each VI group versus placebo (p < 0.001). The effects of once-daily VI on trough FEV(1) and weighted mean 24-h FEV(1) were dose dependent. The incidence of adverse events (AEs) was low in each VI treatment group and was not dose dependent (5-9%; placebo = 18%); no drug-related AEs or serious AEs were reported.
CONCLUSION: Once-daily treatment with VI was well tolerated and associated with improvements in lung function. The VI 6.25 mcg twice-daily dose showed the greatest change in trough FEV(1), however, similar changes in weighted mean 24-h FEV(1) with VI 12.5 mcg once-daily were observed. Although our study was not powered to demonstrate non-inferiority of once- versus twice-daily dosing of VI, the data suggest no advantage over a 24-h period of twice-daily over once-daily dosing for the same total daily dose. ClinicalTrials.gov: NCT00980200.
Respir Med. 2012 Apr 18. [Epub ahead of print]
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