insaf Respiratory Research Institute GmbH, Wiesbaden, Germany.
Respir Res. 2014 Jun 3;15(1):61. doi: 10.1186/1465-9921-15-61.
Tiotropium, a once-daily long-acting anticholinergic bronchodilator, when administered via Respimat® SoftMist™ inhaler (tiotropium Respimat®) significantly reduces the risk of severe exacerbations and improves lung function in patients with severe persistent asthma that is not fully controlled despite using inhaled corticosteroids (ICS) and long-acting β2-agonists. To further explore the dose-response curve in asthma, we investigated the efficacy and safety of three different doses of tiotropium Respimat® as add-on to ICS in symptomatic patients with moderate persistent asthma.
In this randomised, double-blind, placebo-controlled, four-way crossover study, patients were randomised to tiotropium Respimat® 5 μg, 2.5 μg or 1.25 μg or placebo Respimat®, once daily in the evening. Each treatment was administered for 4 weeks, without washout between treatment periods. Eligibility criteria included ≥60% and ≤90% of predicted normal forced expiratory volume in 1 second (FEV1) and seven-question Asthma Control Questionnaire mean score of ≥1.5. Patients were required to continue maintenance treatment with stable medium-dose ICS for at least 4 weeks prior to and during the treatment period. Long-acting β2-agonists were not permitted during the treatment phase. The primary efficacy end point was peak FEV1 measured within 3 hours after dosing (peak FEV1(0-3h)) at the end of each 4-week period, analysed as a response (change from study baseline).
In total, 149 patients were randomised and 141 completed the study. Statistically significant improvements in peak FEV1(0-3h) response were observed with each tiotropium Respimat® dose versus placebo (all P < 0.0001). The largest difference from placebo was with tiotropium Respimat® 5 μg (188 mL). Trough FEV1 and FEV1 area under the curve (AUC)(0-3h) responses were greater with each tiotropium Respimat® dose than with placebo (all P < 0.0001), and both were greatest with 5 μg. Peak forced vital capacity (FVC)(0-3h), trough FVC and FVC AUC(0-3h) responses, versus placebo, were greatest with tiotropium Respimat® 5 μg (P < 0.0001, P = 0.0012 and P < 0.0001, respectively). Incidence of adverse events was comparable between placebo and all tiotropium Respimat® groups.
Once-daily tiotropium Respimat® add-on to medium-dose ICS improves lung function in symptomatic patients with moderate asthma. Overall, improvements were largest with tiotropium Respimat® 5 μg.
ClinicalTrials.gov identifier NCT01233284.
噻托溴铵是一种每日一次的长效抗胆碱能支气管扩张剂，通过 Respimat® SoftMist™吸入器（噻托溴铵 Respimat®）给药，可显著降低严重恶化的风险，并改善未充分控制的重度持续性哮喘患者的肺功能，这些患者即使使用吸入性皮质类固醇（ICS）和长效β2-激动剂也无法得到完全控制。为了进一步探索哮喘的剂量反应曲线，我们研究了噻托溴铵 Respimat®在中度持续性哮喘症状患者中的三种不同剂量与 ICS 联合应用的疗效和安全性。
在这项随机、双盲、安慰剂对照、四向交叉研究中，患者被随机分配至噻托溴铵 Respimat® 5μg、2.5μg 或 1.25μg 或安慰剂 Respimat®，每晚一次。每种治疗持续 4 周，在治疗期间无洗脱期。入选标准包括：预计用力呼气量（FEV1）的 60%至 90%和≥7 项哮喘控制问卷的平均得分≥1.5。患者在治疗期前和治疗期间需要继续使用稳定的中剂量 ICS 维持治疗至少 4 周。在治疗期间不允许使用长效β2-激动剂。主要疗效终点是每个 4 周治疗期结束时测量的峰 FEV1（0-3h）（峰 FEV1（0-3h）），分析为反应（与研究基线相比的变化）。
共有 149 名患者被随机分组，141 名患者完成了研究。与安慰剂相比，噻托溴铵 Respimat®的每个剂量都观察到了峰 FEV1（0-3h）反应的统计学显著改善（均 P<0.0001）。与安慰剂相比，噻托溴铵 Respimat® 5μg 的差异最大（188mL）。与安慰剂相比，每个噻托溴铵 Respimat®剂量的谷 FEV1 和 FEV1 曲线下面积（AUC）（0-3h）反应均更大（均 P<0.0001），5μg 的反应最大。与安慰剂相比，峰用力肺活量（FVC）（0-3h）、谷 FVC 和 FVC AUC（0-3h）反应最大的是噻托溴铵 Respimat® 5μg（P<0.0001、P=0.0012 和 P<0.0001）。安慰剂和所有噻托溴铵 Respimat®组之间不良反应的发生率相当。
噻托溴铵 Respimat®每日一次添加到中剂量 ICS 可改善中度哮喘症状患者的肺功能。总体而言，噻托溴铵 Respimat® 5μg 的改善最大。
ClinicalTrials.gov 标识符 NCT01233284。
