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氟替卡松联合沙美特罗与单用氟替卡松后的严重哮喘事件比较研究
Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone


David A. Stempel ... 呼吸系统疾病 • 2016.05.12
相关阅读
• 增加吸入性糖皮质激素以预防哮喘发作 • 哮喘药物治疗的真实世界疗效比较试验 • 临床实践中糠酸氟替卡松-维兰特罗对COPD治疗的有效性 • 茚达特罗-格隆溴铵与沙美特罗-氟替卡松治疗COPD的比较研究

摘要


背景

长效β受体激动剂(LABA)在哮喘治疗中的安全和合理用药受到广泛争议。在两项大型临床试验中,研究人员发现LABA有伴发严重哮喘相关事件的潜在风险。本研究旨在评估联合使用LABA沙美特罗与吸入型糖皮质激素丙酸氟替卡松的风险。

 

方法

在这项多中心、随机的双盲试验中,患持续性哮喘的青少年和成人患者(年龄≥12岁)被分为两组,一组接受沙美特罗联合氟替卡松治疗,另一组则单独接受氟替卡松治疗,治疗期为26周。所有患者在随机化前的一年内均有重度哮喘加重的病史,但在最近一个月内未出现该情况。本试验排除了有致命性哮喘或不稳定性哮喘病史的患者。主要安全性终点为首次出现严重哮喘相关事件(死亡、气管插管或住院治疗)。我们将氟替卡松-沙美特罗与单用氟替卡松相比的非劣效性定义为,对于主要安全性终点的风险,95%置信区间的上界小于2.0。疗效终点为首次发生重度哮喘加重。

 

结果

在研究纳入的11,679例患者中,67例患者出现严重哮喘相关事件74起,其中氟替卡松-沙美特罗组34例患者出现相关事件36起,氟替卡松组33例患者出现相关事件38起。氟替卡松-沙美特罗组的严重哮喘相关事件的风险比为1.03(95%置信区间[CI],0.64~1.66),达到非劣效性标准(P=0.003)。本试验没有出现哮喘相关的死亡病例;单用氟替卡松组的2例患者接受哮喘相关插管。氟替卡松-沙美特罗组出现重度哮喘加重的风险比单用氟替卡松组低21%(风险比0.79;95% CI,0.70~0.89),单用氟替卡松组5,834例患者中有597例(10%)出现至少一次重度哮喘加重;与之相比,氟替卡松-沙美特罗组的5,834例患者中有480例(8%)出现相同情况(P<0.001)。

 

结论

与单用氟替卡松的患者相比,接受沙美特罗-氟替卡松固定剂量联合治疗的患者出现严重哮喘相关事件的风险并未显著较高。与单用氟替卡松的患者相比,接受氟替卡松-沙美特罗联合治疗的患者出现的重度哮喘加重较少(AUSTRI ClinicalTrials.gov注册号为NCT01475721)。





作者信息

David A. Stempel, M.D., Ibrahim H. Raphiou, Ph.D., Kenneth M. Kral, M.S., Anne M. Yeakey, M.D., Amanda H. Emmett, M.S., Charlene M. Prazma, Ph.D., Kathleen S. Buaron, B.S.N., and Steven J. Pascoe, M.B., B.S., for the AUSTRI Investigators*
From Respiratory Clinical Development (D.A.S., I.H.R., A.M.Y., C.M.P., K.S.B., S.J.P.) and Research and Development, Clinical Platforms and Sciences, Clinical Statistics (K.M.K., A.H.E.), GlaxoSmithKline, Durham, NC.Address reprint requests to Dr. Stempel at Respiratory Clinical Development, GlaxoSmithKline, 5 Moore Dr., P.O. Box 13398, Research Triangle Park, Durham, NC 27709, or at david.a.stempel@gsk.com. *A complete list of investigators in the AUSTRI trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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