噻托溴铵吸入胶囊与异丙托溴铵定量气雾剂治疗慢性阻塞性肺疾病的随机、双盲、双模拟疗效和安全性研究比较

[Comparison of tiotropium inhalation capsules and ipratropium metered dose inhaler in a randomized, double-blind, double-dummy, efficacy and safety study in patients with chronic obstructive pulmonary disease].

作者信息

Zheng Jin-ping, Kang Jian, Cai Bai-qiang, Zhou Xin, Cao Zhao-long, Bai Chun-xue, Zhong Nan-shan

机构信息

Guangzhou Institute of Respiratory Disease, First Hospital Affiliated, Guangzhou Medical College, Guangzhou 510120, China.

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2006 Jun;29(6):363-7.

PMID:17045014

Abstract

OBJECTIVE

To compare the efficacy and safety between tiotropium capsule and ipratropium MDI in a 4 week treatment in patients with chronic obstructive pulmonary disease (COPD).

METHODS

A multi-center, randomized, double blind, double dummy and parallel comparison clinical trial was conducted in 221 stable moderate to severe patients with COPD. They were randomized into tiotropium 18 microg once per day arm or ipratropium 2 puffs qid. arm for four weeks. The spirometry was conducted at 5 minutes pre-medication; and 30, 60, 120, and 180 minutes post-medication before; 2 weeks and 4 weeks after treatment.

RESULTS

The forced expiratory volume in one second (FEV(1)) trough response, the primary endpoint, was significantly higher in the tiotropium arm than that of the ipratropium with (0.063 +/- 0.024) L (95% CI 0.016 - 0.111 L, t = 2.63, P = 0.009) after 4 weeks of treatment. Meanwhile the clinical evidences indicated the continuous improvement of bronchodilation in the tiotropium arm. Forced vital capacity (FVC) trough response was also significantly higher in the tiotropium arm 4 weeks after treatment with (0.133 +/- 0.047) L (t = 2.83, P = 0.005). By comparison with baseline, no significant differences were found between these two arms in the average change of FEV(1) as well as FVC 0 - 3 hours after inhalation (all P > 0.05). There was no significant difference in rescue medication consumptions (t = 0.60, P = 0.548). Adverse events occurred in 12 (10.9%) patients in the tiotropium arm and 18 (16.2%) in the ipratropium arm, without statistical difference (chi(2) = 1.326, P = 0.249). The major adverse event in the tiotropium group was dry mouth (5, 4.5%). No cardiac disorder or abnormal electrocardiogram was reported.

CONCLUSION

The results indicated that tiotropium 18 microg once per day is more potent than ipratropium qid. in bronchodilation to COPD patients with the similar tolerance of ipratropium.

摘要

目的

比较噻托溴铵胶囊与异丙托溴铵气雾剂治疗慢性阻塞性肺疾病（COPD）患者4周的疗效与安全性。

方法

对221例病情稳定的中重度COPD患者进行一项多中心、随机、双盲、双模拟和平行对照临床试验。将他们随机分为噻托溴铵18μg每日1次组或异丙托溴铵每次2喷每日4次组，治疗4周。在用药前5分钟、用药后30、60、120和180分钟、治疗前、治疗2周和4周时进行肺功能测定。

结果

治疗4周后，主要终点指标1秒用力呼气容积（FEV(1)）谷值反应在噻托溴铵组显著高于异丙托溴铵组，为（0.063±0.024）L（95%CI 0.016 - 0.111 L，t = 2.63，P = 0.009）。同时临床证据表明噻托溴铵组支气管扩张作用持续改善。治疗4周后噻托溴铵组用力肺活量（FVC）谷值反应也显著更高，为（0.133±0.047）L（t = 2.83，P = 0.005）。与基线相比，两组吸入后0 - 3小时FEV(1)以及FVC的平均变化无显著差异（均P > 0.05）。急救药物消耗量无显著差异（t = 0.60，P = 0.548）。噻托溴铵组12例（10.9%）患者发生不良事件，异丙托溴铵组18例（16.2%），无统计学差异（χ(2) = 1.326，P = 0.249）。噻托溴铵组主要不良事件为口干（5例，4.5%）。未报告心脏疾病或心电图异常。