Wolfe J D, Selner J C, Mendelson L M, Hampel F, Schaberg A
Allergy and Asthma Associates of Santa Clara Valley, San Jose, California, USA.
Clin Ther. 1996 Jul-Aug;18(4):635-46. doi: 10.1016/s0149-2918(96)80214-1.
This study was undertaken to evaluate the efficacy and safety of fluticasone propionate, an inhaled corticosteroid, in adolescents and adults with moderate asthma who were previously taking inhaled corticosteroids. After a 2-week, open-label screening period, a double-masked, randomized, parallel-group, dose-ranging study was conducted over 12 weeks in 21 outpatient centers throughout the United States. Patients (N = 304) > or = 12 years of age with moderate asthma previously treated with inhaled corticosteroids and beta-sympathomimetic bronchodilators were enrolled. Patients were assigned to receive placebo or fluticasone propionate 100, 250, or 500 micrograms twice daily via a metered-dose inhaler without a spacer device. These doses refer to the amount of fluticasone propionate released from the valve of the metered-dose inhaler; the corresponding doses released from the activator of the metered-dose inhaler are 88 micrograms, 220 micrograms, and 440 micrograms, respectively. Between baseline and end point, mean values of forced expiratory volume in 1 second decreased 0.31 L in the placebo group and improved 0.39 L, 0.30 L, and 0.43 L in patients receiving 100-micrograms, 250-micrograms, and 500-micrograms fluticasone propionate, respectively. The differences between placebo and all treatment groups were statistically significant. More patients were withdrawn from placebo (72%) than from fluticasone propionate (13% to 16%) because of failure to meet predetermined asthma stability criteria. Differences in baseline-to-end point changes in morning peak expiratory flow rate, physician overall assessments and patient-rated assessment of symptoms, and albuterol use for symptom control also significantly favored each fluticasone propionate group over placebo. There were essentially no differences in efficacy among the three fluticasone propionate groups. Treatment-related adverse events occurred in 8% of placebo-treated patients and 13% to 15% of fluticasone propionate-treated patients; these events were mainly localized to the oropharynx/ larynx. A 12-week course of fluticasone propionate (100, 250, and 500 micrograms twice daily) was well tolerated and more effective than placebo based on maintenance of asthma stability, pulmonary function tests, physician and patient assessments, and rescue bronchodilator use. No dose-related effects were observed with the dosages of fluticasone propionate used in this study.
本研究旨在评估吸入性皮质类固醇丙酸氟替卡松对曾使用吸入性皮质类固醇的中度哮喘青少年和成人的疗效及安全性。在为期2周的开放标签筛查期后，在美国21个门诊中心进行了一项为期12周的双盲、随机、平行组、剂量范围研究。纳入年龄≥12岁、曾使用吸入性皮质类固醇和β-拟交感神经支气管扩张剂治疗的中度哮喘患者（N = 304）。患者被分配接受安慰剂或每日两次通过无储雾罐的定量吸入器吸入100、250或500微克丙酸氟替卡松。这些剂量指从定量吸入器阀门释放的丙酸氟替卡松量；从定量吸入器启动器释放的相应剂量分别为88微克、220微克和440微克。在基线和终点之间，安慰剂组1秒用力呼气量平均值下降0.31升，接受100微克、250微克和500微克丙酸氟替卡松的患者分别改善0.39升、0.30升和0.43升。安慰剂组与所有治疗组之间的差异具有统计学意义。因未达到预定的哮喘稳定性标准，退出安慰剂组的患者（72%）多于退出丙酸氟替卡松组的患者（13%至16%）。早晨呼气峰值流速、医生总体评估和患者症状评分以及用于症状控制的沙丁胺醇使用情况从基线到终点的变化差异也显著有利于各丙酸氟替卡松组而非安慰剂组。三个丙酸氟替卡松组之间的疗效基本无差异。治疗相关不良事件在接受安慰剂治疗的患者中发生率为8%，在接受丙酸氟替卡松治疗的患者中为13%至15%；这些事件主要局限于口咽/喉部。基于哮喘稳定性的维持、肺功能测试、医生和患者评估以及急救支气管扩张剂的使用，为期12周疗程的丙酸氟替卡松（每日两次，100、250和500微克）耐受性良好且比安慰剂更有效。本研究中使用的丙酸氟替卡松剂量未观察到剂量相关效应。
