经Respimat(R)吸入小剂量噻托溴铵溶液治疗慢性阻塞性肺疾病的有效性与安全性

摘要

目的 评价经Respimat(R)吸入5μg噻托溴铵溶液治疗慢性阻塞性肺疾病(COPD)患者48周的有效性与安全性.方法 随机、双盲、安慰剂对照平行临床研究.入选的338例COPD患者随机分为噻托溴铵组和安慰剂组,噻托溴铵组每天经Respimat(R)吸入噻托溴铵溶液5μg(2×2.5 μg/喷),安慰剂组每天经Respimat(R)吸入安慰剂2喷,研究周期48周,主要观察终点为治疗4周、24周、48周后的第1秒用力呼气容积(FEV1)谷值及首次出现COPD急性加重时间.结果 295例患者完成临床研究,噻托溴铵组151例,安慰剂组144例.与安慰剂组比,第4周、24周、48周噻托溴铵组FEV1谷值和FVC谷值有明显改善,两组差异有统计学意义(P ＜0.000 1).首次出现COPD急性加重时间噻托溴铵组157 d,对照组85 d,两组比较差异有统计学意义(P=0.0027).COPD急性加重次数噻托溴铵组为90例次,安慰剂组为128例次;急性加重发生率噻托溴铵组为0.67次/人年,安慰剂组为0.98次/人年,两组差异有统计学意义(RR=0.69,95％ CI0.50～ 0.93,P=0.0164).2组患者治疗48周后,噻托溴铵组圣乔治呼吸问卷总评分、症状评分、活动评分改善优于安慰剂组(P=0.036 7).与药物相关的不良反应噻托溴铵组12例,安慰剂组11例.结论 噻托溴铵能显著改善COPD患者的肺功能和生活质量,延缓首次急性加重时间,减少急性加重次数,具有较好的耐受性.%Objective To compare the efficacy and safety of long-term treatment (48 weeks) with tiotropium bromide (5 μg) via Respimat(R) with placebo in patients with chronic obstructive pulmonary disease (COPD).Methods A total of 338 patients were randomized in this double-blind,placebo controlled,parallel study.All patients received either tiotropium bromide or placebo.Tiotropium bromide solution 5 μg (2 × 2.5 μg/puff) or matching placebo was delivered via Respimat(R) at a dosage of once daily for 48 weeks.Co-primary endpoints were trough forced expiratory volume in one second (FEV1) and the time to first exacerbation.Results Statistically significant improvements of both trough FEV1 and trough forced vital capacity (FVC) in the tiotropium group were achieved at weeks 4,24,and 48 compared with those in the placebo group(P ＜ 0.000 1).Tiotropium treatment delayed the time to first exacerbation.The time was 157 days in the tiotropium group and 85 days in the placebo group.A statistically significant difference (P =0.002 7) in favor of tiotropium was also observed.The total numbers of exacerbation during treatment were 90 and 128 in the tiotropium and placebo groups,respectively.The Poisson regression analysis gave a mean exacerbation rate per patient year exposure of 0.67 in the tiotropium group compared to 0.98 in the placebo group with a rate ratio of 0.69 (95％ CI O.50-0.93,P =0.016 4).A much larger improvement from baseline in St.George's respiratory questionnaire (SGRQ) total score was observed for the tiotropium group than in the placebo group(P =0.036 7),SGRQ symptom and activity scores of patients in the tiotropium group were also superior to those of patients receiving placebo.The drugs-related adverse events in the tiotropium and placebo groups were 12 cases and 11 cases,respectively.Conclusions Tiotropium significantly improved lung function and quality of life,delayed the time to first exacerbation,reduced the number of exacerbation.Overall,tiotropium was well tolerated.