A randomised controlled comparison of tiotropium nd ipratropium in the treatment of chronic obstructive pulmonary disease. The Dutch Tiotropium Study Group.
A randomised controlled comparison of tiotropium nd ipratropium in the treatment of chronic obstructive pulmonary disease. The Dutch Tiotropium Study Group.
复制标题
噻托溴铵和异丙托溴铵治疗慢性阻塞性肺疾病的随机对照比较。
作者：
J. V. van Noord;T. Bantje;M. Eland;L. Korducki;P. Cornelissen
背景
开展了一项研究，以评价和比较噻托溴铵和异丙托溴铵在稳定期慢性阻塞性肺疾病（COPD）患者长期治疗期间的疗效和安全性。
方法
288例平均（SD）年龄65（8）岁、1秒用力呼气量（FEV（1））41（12）%预测值的患者参加了一项14个中心、双盲、双模拟、平行组研究，并在两周的导入期后随机接受噻托溴铵18 μ g，每日一次，通过干粉吸入器吸入（吸乐;三分之二的患者）或异丙托溴铵40 μ g，每日4次，从定量吸入器（三分之一的患者）吸入，持续13周。结果指标为肺功能、每日最大呼气流量（PEF）记录和沙丁胺醇的伴随使用。吸入前1h及吸入前即刻测定FEV 1和用力肺活量（FVC）（试验第1天的两次测量的平均值为基线值，而在所有其他试验日，其被称为FEV（1）和FVC谷值），以及第1、8、50和92天吸入研究药物后0.5、1、2、3、4、5和6小时。
结果
在治疗期间，噻托溴铵对FEV（1）谷值、平均值和峰值水平以及FVC谷值和平均值水平的改善显著大于异丙托溴铵（p<0.05）。第8、50和92天，噻托溴铵组的FEV（1）谷值反应范围为0.15 l（95% CI 0.11 - 0.19）至0.16 l（95% CI 0.12 - 0.20），噻托溴铵组的FEV（1）谷值反应范围为0.01 l（95% CI -0.03至0.05）至0.03 l（95% CI 0.01 - 0.20）。07)异丙托溴铵噻托溴铵组第8、50和92天的FVC谷值反应范围为0.34 l（95% CI 0.28 - 0.40）至0.39 l（95% CI 0.31 - 0.47），异丙托溴铵组为0.08 l（95% CI 0.00 - 0.16）至0.18 l（95% CI 0.08 - 0.28）。在所有试验日，吸入后3小时开始，噻托溴铵对FEV（1）的改善大于异丙托溴铵（p<0.05）。治疗期间，噻托溴铵组每周平均晨间和夜间呼气峰流速（PEF）始终优于异丙托溴铵组，晨间PEF差异显著，直至治疗第10周，夜间PEF差异显著，直至治疗第7周（p<0.05）。噻托溴铵组同时使用沙丁胺醇的比例也较低（p<0.05）。唯一的药物相关不良事件为口干（噻托溴铵组14.7%，异丙托溴铵组10.3%）。
结论
在13周期间，噻托溴铵18 μ g吸乐每日一次吸入治疗在改善谷值、平均值和峰值肺功能方面显著优于异丙托溴铵40 μ g每日四次。噻托溴铵的安全性特征与异丙托溴铵相似。这些数据支持将噻托溴铵用作COPD所致气流阻塞患者的一线长期维持治疗。
BACKGROUND
A study was undertaken to evaluate and compare the efficacy and safety of tiotropium and ipratropium during long term treatment in patients with stable chronic obstructive pulmonary disease (COPD).
METHODS
288 patients of mean (SD) age 65 (8) years and forced expiratory volume in one second (FEV(1)) 41 (12)% predicted participated in a 14 centre, double blind, double dummy, parallel group study and were randomised after a run in period of two weeks to receive either tiotropium 18 microg once daily from a dry powder inhaler (HandiHaler; two thirds of patients) or ipratropium 40 microg four times daily from a metered dose inhaler (one third of patients) for a period of 13 weeks. Outcome measures were lung function, daily records of peak expiratory flow (PEF), and the use of concomitant salbutamol. FEV(1) and forced vital capacity (FVC) were measured one hour before and immediately before inhalation (mean value of the two measurements on test day 1 was the baseline value while on all other test days it was known as the trough FEV(1) and FVC), and 0.5, 1, 2, 3, 4, 5, and 6 hours after inhalation of the study drug on days 1, 8, 50, and 92.
RESULTS
During treatment tiotropium achieved a significantly greater improvement than ipratropium (p<0.05) in trough, average, and peak FEV(1) levels and in trough and average FVC levels. The trough FEV(1) response on days 8, 50, and 92 ranged between 0.15 l (95% CI 0.11 to 0.19) and 0.16 l (95% CI 0.12 to 0.20) for tiotropium and between 0.01 l (95% CI -0.03 to 0.05) and 0.03 l (95% CI 0.01 to 0. 07) for ipratropium. The trough FVC response on days 8, 50, and 92 ranged between 0.34 l (95% CI 0.28 to 0.40) and 0.39 l (95% CI 0.31 to 0.47) for tiotropium and between 0.08 l (95% CI 0.00 to 0.16) and 0.18 l (95% CI 0.08 to 0.28) for ipratropium. On all test days tiotropium produced a greater improvement in FEV(1) than ipratropium starting three hours after inhalation (p<0.05). During treatment weekly mean morning and evening peak expiratory flow (PEF) was consistently better in the tiotropium group than in the ipratropium group, the difference in morning PEF being significant up through week 10 and in evening PEF up through week 7 of treatment (p<0.05). The use of concomitant salbutamol was also lower in the tiotropium group (p<0.05). The only drug related adverse event was dry mouth (tiotropium 14.7%, ipratropium 10.3% of patients).
CONCLUSIONS
Tiotropium in a dose of 18 microg inhaled once daily using the HandiHaler was significantly more effective than 40 microg ipratropium four times daily in improving trough, average, and peak lung function over the 13 week period. The safety profile of tiotropium was similar to ipratropium. These data support the use of tiotropium as first line treatment for the long term maintenance treatment of patients with airflow obstruction due to COPD.