Academic Hospital, University of Brussels (AZVUB), Brussels, Belgium.
Clin Drug Investig. 2004;24(1):17-28. doi: 10.2165/00044011-200424010-00003.
Respimat((R)) Soft Misttrade mark Inhaler (SMI) is a novel, propellant-free device that significantly increases lung deposition compared with pressurised metered-dose inhalers (pMDIs). The aim of this study was to compare the efficacy and safety of ipratropium bromide/fenoterol hydrobromide (IB/FEN; Berodual((R))) delivered via Respimat((R)) SMI and via a chlorofluorocarbon (CFC)-driven pMDI (CFC-MDI) in patients with asthma.
Multicentre, randomised, double-blind, placebo-controlled, parallel- group study.
631 patients (18-65 years old) with stable asthma.
After a 2-week run-in period (IB/FEN 20mug/50mug via CFC-MDI, two actuations four times a day), patients were randomised to 12 weeks' treatment with one of five treatments: IB/FEN 10mug/25mug, 20mug/50mug or placebo via Respimat((R)) SMI (one actuation four times a day), or IB/FEN 20mug/50mug or placebo via CFC-MDI (two actuations four times a day). The main efficacy measure was lung function (assessed on days 1, 29, 57 and 85); safety was assessed by monitoring adverse events.
Bronchodilator responses to IB/FEN were much greater than those to placebo (mean peak increases in forced expiratory volume in 1 second [FEV(1)] on day 85: 0.498-0.521L, active treatment; 0.215 and 0.240L, placebo). According to the primary endpoint, i.e. the average change in FEV(1) from test-day baseline over the 6 hours after dosing on day 85, neither IB/FEN dosage via Respimat((R)) SMI was inferior to IB/FEN via pMDI (p < 0.001). Non-inferiority of the two Respimat((R)) SMI dosages was supported by analyses of other lung function measures, e.g. average change in FEV(1) from test-day baseline over the 6 hours after dosing on the other 3 test days, and peak FEV(1) on all test days. Overall, the safety profile of IB/FEN via Respimat((R)) SMI was comparable to that via CFC-MDI.
IB/FEN from Respimat((R)) SMI is as effective and safe as from CFC-MDI and enables a 2- to 4-fold daily dose reduction of IB/FEN.
Respimat((R)) 软雾吸入器（SMI）是一种新型的无推进剂装置，与压力定量吸入器（pMDI）相比，它能显著增加肺部沉积。本研究旨在比较布地奈德/福莫特罗氢溴酸盐（IB/FEN；Berodual((R)))经 Respimat((R)) SMI 和经氯氟烃（CFC）驱动的 pMDI（CFC-MDI）给药在哮喘患者中的疗效和安全性。
多中心、随机、双盲、安慰剂对照、平行组研究。
631 例（18-65 岁）稳定期哮喘患者。
经过 2 周的导入期（CFC-MDI 给予 IB/FEN20mug/50mug，每天 4 次，每次 2 次），患者随机接受 12 周的治疗，分为 5 种治疗方案之一：Respimat((R)) SMI 给予 IB/FEN10mug/25mug、20mug/50mug 或安慰剂（每天 4 次，每次 1 次），或 CFC-MDI 给予 IB/FEN20mug/50mug 或安慰剂（每天 4 次，每次 2 次）。主要疗效指标为肺功能（在第 1、29、57 和 85 天评估）；安全性通过监测不良事件进行评估。
IB/FEN 的支气管扩张作用明显大于安慰剂（第 85 天用力呼气量第一秒的平均峰值增加[FEV1]：0.498-0.521L，活性治疗；0.215 和 0.240L，安慰剂）。根据主要终点，即第 85 天给药后 6 小时内 FEV1 从试验日基线的平均变化，IB/FEN 经 Respimat((R)) SMI 给药的两种剂量均不劣于 IB/FEN 经 pMDI 给药（p < 0.001）。Respimat((R)) SMI 的两种剂量均具有非劣效性，这得到了其他肺功能指标的分析支持，例如在其他 3 个试验日给药后 6 小时内 FEV1 从试验日基线的平均变化，以及所有试验日的最大 FEV1。总体而言，IB/FEN 经 Respimat((R)) SMI 给药的安全性与 CFC-MDI 给药相当。
布地奈德/福莫特罗氢溴酸盐经 Respimat((R)) SMI 给药与经 CFC-MDI 给药同样有效且安全，并且能够使布地奈德/福莫特罗氢溴酸盐的每日剂量减少 2 至 4 倍。
