吸入噻托溴铵干粉与异丙托溴铵定量气雾剂治疗慢性阻塞性肺疾病的疗效与安全性比较

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

目的比较噻托溴铵干粉吸入剂与异丙托溴铵定量气雾剂治疗慢性阻塞性肺疾病(COPD)4周的疗效与安全性。方法采用多中心、随机、双盲、双模拟、平行对照研究方法,对221例筛选合格的稳定期中重度COPD患者给予吸入噻托溴铵干粉剂(18μg,每日1次)或异丙托溴铵定量气雾剂(2喷/次,每日4次)治疗4周。在治疗前,治疗后2周及4周,给药前5min,给药后30、60、120及180min分别测定肺功能。结果首要疗效指标第一秒用力呼气容积(FEV1)谷值反应。治疗4周后噻托溴铵组FEV1谷值反应显著优于异丙托溴铵组[(0.063±0.024)L,95%CI为0.016～0.111L,t=2.63,P=0.009],显示噻托溴铵组患者的通气功能得到持续改善;噻托溴铵组的用力肺活量(FVC)谷值反应在治疗4周时较异丙托溴铵组增高(0.133±0.047)L,t=2.83,P=0.005;与基线相比,给药后0～3h平均FEV1的变化(FEV1AUC0～3h)及平均FVC变化(FVCAUC0～3h)在两组比较差异均无统计学意义;缓解喘息应急药物的使用量在两组间比较差异无统计学意义(t=0.60,P=0.548)。本研究中噻托溴铵组有12例(10.9%)、异丙托溴铵组有18例(16.2%)发生不良事件,两组比较差异无统计学意义(χ2=1.326,P=0.249)。噻托溴铵的常见不良反应为口干(5例,4.5%),无心血管系统异常和心电图异常报告。结论每日1次吸入噻托溴铵18μg较每日4次异丙托溴铵治疗,对COPD患者具有更强的支气管扩张作用。噻托溴铵耐受性良好,与异丙托溴铵具有相似的安全性。

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 μg once per day ann or ipratropium 2 puffs qid. ann 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 （FEVl ） trough response, the primary endpoint, was significantly higher in the tiotropium ann 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 FEVt 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 occured in 12 （ 10. 9% ） patients in the tiotropium arm and 18 （ 16. 2% ） in the ipmtropium arm, without statistical difference （ χ^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 18μg once per day is more potent than ipratropium qid. in bronchodilation to COPD patients with the similar tolerance of ipratropium.