哮喘联盟

   摘要
   背景：本研究为一项II期、多中心、随机、双盲、安慰剂对照、交叉试验，比较了采用Respimat®给予中重度哮喘患者每天1次（QD）或每天2次（BID）奥达特罗（每日总剂量相同）或安慰剂治疗3周后的24小时1秒用力呼气容积（FEV1）时间分布。
   方法：患者被随机分为两组，分别接受不同顺序的奥达特罗治疗，洗脱期为2周，一组接受总剂量为5ug（5ug QD或2.5ug BID）或安慰剂的治疗，另一组接受总剂量为10ug（10ug QD或5ug BID）或安慰剂的治疗。主要终点为3周后的FEV1 0-24小时曲线下面积(AUC0-24)反应（定义为FEV1自研究基线的变化）。次要终点为FEV1 AUC0-12 和AUC12-24 反应。
   结果：共206例患者接受了治疗。与安慰剂相比，奥达特罗治疗3周后能显著改善患者的FEV1 AUC0-24 反应(p<0.0001)；与安慰剂比较，校正后的平均治疗差异为：奥达特罗2.5 μg BID为0.191L(95%可信区间 [CI] 0.152, 0.229)，5 μg QD为0.150L(95 % CI 0.111, 0.189)，5 μg BID为0.228L(95 % CI 0.190, 0.266)，10μg QD为0.209L(95% CI 0.170, 0.247)。次要终点支持这些结果。奥达特罗5μg QD比2.5μg BID的24小时支气管扩张平均值低(p=0.0465)，奥达特罗10μg QD和5μg QD治疗效果无统计学差异。治疗3周后，在早晨和晚上呼气流速峰值和哮喘控制问卷得分方面，不同剂量和方案无差异。各组间不良反应为轻到中度且程度相当。
   结论：所有的剂量和方案都能提供充足的优于安慰剂的24小时支气管扩张。基于本研究的结果，在以后的试验中给予每天5μg奥达特罗（5μg QD或2.5μg BID，通过Respimat® 吸入器给药）处理是合理的。需要进一步的研究以明确哮喘治疗的最佳给药方案。无安全问题需要指出。
 

（杨冬 审校）
Respir Res. 2015 Jul 16;16(1):87. [Epub ahead of print]

 

Randomised, double-blind, placebo-controlled crossover study to investigate different dosing regimens of olodaterol delivered via Respimat® in patients with moderate to severe persistent asthma.
 

Beeh KM1, LaForce C2, Gahlemann M3, Wenz A4, Toorawa R5, Fležar M6.
 

Abstract
BACKGROUND:A Phase II, multicentre, randomised, double-blind, placebo-controlled, crossover trial comparing the 24-h forced expiratory volume in 1 s (FEV1) time profile after 3 weeks' treatment with once-daily (QD) or twice-daily (BID) olodaterol (at the same total daily dose) versus placebo delivered via Respimat® in patients with moderate to severe asthma.
METHODS:Patients were randomised to different sequences of olodaterol with 2-week washout, either as a total daily dose of 5 μg (5 μg QD [AM] or 2.5 μg BID) or placebo, or 10 μg (10 μg QD [AM] or 5 μg BID) or placebo. Primary end point was FEV1 area under the curve from 0 to 24 h (AUC0-24) response (defined as change from study baseline FEV1) after 3 weeks. Key secondary end points were FEV1 AUC0-12 and AUC12-24 responses.
RESULTS:Two hundred six patients received treatment. All olodaterol treatments demonstrated statistically significant improvements in FEV1 AUC0-24 response at 3 weeks versus placebo (p < 0.0001); adjusted mean treatment difference versus placebo was 0.191 L for olodaterol 2.5 μg BID (95 % confidence interval [CI] 0.152, 0.229), 0.150 L for 5 μg QD (95 % CI 0.111, 0.189), 0.228 L for 5 μg BID (95 % CI 0.190, 0.266) and 0.209 L for 10 μg QD (95 % CI 0.170, 0.247). These results were supported by the key secondary end points. Olodaterol 5 μg QD provided numerically lower mean values for 24-h bronchodilation than olodaterol 2.5 μg BID (p = 0.0465), with no statistically significant difference between treatment with olodaterol 10 μg QD and 5 μg BID. No relevant differences in morning and evening peak expiratory flow or Asthma Control Questionnaire scores at 3 weeks were observed between different doses and regimens. Adverse events were generally mild to moderate and comparable between groups.
CONCLUSIONS:All doses and dose frequencies provided adequate 24-h bronchodilation superior to placebo. Based on the results of this study, it would be reasonable to include both posologies of 5 μg olodaterol daily (5 μg QD or 2.5 μg BID, both delivered in two puffs per dose from the Respimat® inhaler) in subsequent studies. Further studies are necessary to confirm the optimum dosing regimen in asthma. No safety concerns were identified.
 

Respir Res. 2015 Jul 16;16(1):87. [Epub ahead of print]