Rabe Klaus F, Timmer Wolfgang, Sagkriotis Alexandros, Viel Klaus
Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands.
Boehringer Ingelheim Pharma, Ingelheim, Germany.
Chest. 2008 Aug;134(2):255-262. doi: 10.1378/chest.07-2138. Epub 2008 Apr 10.
A 6-week, multicenter, randomized, double-blind, parallel-group study was conducted in patients with COPD to compare lung function improvements of tiotropium, 18 microg qd, plus formoterol, 12 microg bid, to salmeterol, 50 microg bid, plus fluticasone, 500 microg bid.
Following a screening visit, subjects entered a run-in period in which they received regular ipratropium. At randomization, patients were assigned to either tiotropium plus formoterol or salmeterol plus fluticasone. After 6 weeks of treatment, a 12-h lung function profile was obtained. The coprimary end points were FEV(1) area under the curve for the time period 0 to 12 h (AUC(0-12)) and peak FEV(1).
A total of 729 patients were screened, and 605 patients were randomized and treated. A total of 592 patients (baseline FEV(1), 1.32 +/- 0.43 L/min [+/-SD]) were included in the analysis. After 6 weeks, the 12-h lung function profiles in the group receiving tiotropium plus formoterol were superior to those in the group receiving salmeterol plus fluticasone (mean difference in FEV(1) AUC(0-12), 78 mL [p = 0.0006]; mean difference in FVC AUC(0-12), 173 mL, p < 0.0001). Also, peak responses were in favor of tiotropium plus formoterol (difference in peak FEV(1), 103 mL [p < 0.0001]; difference in peak FVC, 214 mL [p < 0.0001]), as were FEV(1) and FVC at each individual time point after dose (p < 0.05). Predose FVC was significantly higher with the bronchodilator combination, while predose FEV(1) and rescue medication use did not differ significantly between groups. Both treatments were well tolerated.
Tiotropium plus formoterol was superior in lung function over the day compared to salmeterol plus fluticasone in patients with moderate COPD. Long-term studies in patients with severe COPD are warranted to assess the relative efficacy of different treatment combinations.
Clinicaltrials.gov Identifier: NCT00239421.
开展了一项为期6周的多中心、随机、双盲、平行组研究，以比较噻托溴铵（每日18微克）联合福莫特罗（每日两次，每次12微克）与沙美特罗（每日两次，每次50微克）联合氟替卡松（每日两次，每次500微克）对慢性阻塞性肺疾病（COPD）患者肺功能的改善情况。
在筛选访视后，受试者进入导入期，在此期间他们接受常规异丙托溴铵治疗。随机分组时，患者被分配至噻托溴铵联合福莫特罗组或沙美特罗联合氟替卡松组。治疗6周后，获取12小时肺功能曲线。共同主要终点为0至12小时时间段内第1秒用力呼气容积（FEV₁）曲线下面积（AUC₀₋₁₂）和FEV₁峰值。
共筛选了729例患者，605例患者被随机分组并接受治疗。共有592例患者（基线FEV₁为1.32±0.43升/分钟[±标准差]）纳入分析。6周后，接受噻托溴铵联合福莫特罗组的12小时肺功能曲线优于接受沙美特罗联合氟替卡松组（FEV₁ AUC₀₋₁₂的平均差值为78毫升[p = 0.0006]；用力肺活量（FVC）AUC₀₋₁₂的平均差值为173毫升，p < 0.0001）。此外，峰值反应也有利于噻托溴铵联合福莫特罗组（FEV₁峰值差值为103毫升[p < 0.0001]；FVC峰值差值为214毫升[p < 0.0001]），给药后各时间点的FEV₁和FVC也是如此（p < 0.05）。支气管扩张剂联合治疗组的给药前FVC显著更高，而给药前FEV₁和急救药物使用在两组间无显著差异。两种治疗耐受性均良好。
在中度COPD患者中，与沙美特罗联合氟替卡松相比，噻托溴铵联合福莫特罗在日间肺功能方面更优。有必要对重度COPD患者进行长期研究，以评估不同治疗组合的相对疗效。
Clinicaltrials.gov标识符：NCT00239421。
