福莫特罗干粉吸入剂与沙美特罗干粉吸入剂治疗中度慢性阻塞性肺疾病的起效时间比较：一项随机、安慰剂对照、双盲、交叉研究。

Onset of action of formoterol versus salmeterol via dry powder inhalers in moderate chronic obstructive pulmonary disease: a randomized, placebo-controlled, double-blind, crossover study.

机构信息

Unit of Respiratory Clinical Pharmacology, Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy.

出版信息

Clin Drug Investig. 2012 Mar 1;32(3):147-55. doi: 10.2165/11630880-000000000-00000.

DOI:10.2165/11630880-000000000-00000

PMID:22235841

Abstract

BACKGROUND

Bronchodilator therapy is central to the symptomatic management of chronic obstructive pulmonary disease (COPD), and treatment with short-acting bronchodilators is recommended in patients with mild COPD.

OBJECTIVE

This study aimed to evaluate the onset of effect of single-dose formoterol 9 μg versus single-dose salmeterol 50 μg in patients with moderate COPD.

METHODS

In this multicentre, double-blind, double-dummy, placebo-controlled, three-way single-dose crossover study, patients ≥40 years of age with moderate COPD were randomized to single-dose formoterol 9 μg via Turbuhaler® plus placebo via Diskus®, single-dose salmeterol 50 μg via Diskus® plus placebo via Turbuhaler® or placebo via Turbuhaler® and Diskus® (washout period 2-7 days). Terbutaline 0.5 mg/actuation via Turbuhaler® was used as reliever medication throughout. The primary endpoint was forced expiratory volume in 1 second (FEV₁) at 5 minutes post-dose. Secondary endpoints included proportion of patients achieving ≥12% increase in FEV₁ at 5 minutes post-dose.

RESULTS

109 patients were randomized, and 108 completed the study. The increase in FEV₁ 5 minutes post-dose versus pre-dose was 7.2% for formoterol, 4.1% for salmeterol and 0.7% for placebo, and significantly greater for formoterol versus salmeterol (ratio of treatment effects: 1.030; 95% CI 1.008, 1.052; p = 0.009), for formoterol versus placebo (1.064, 95% CI 1.041, 1.087; p < 0.001) and for salmeterol versus placebo (1.033, 95% CI 1.011, 1.056; p = 0.003). The proportions of patients with ≥12% increase in FEV₁ 5 minutes post-dose were 23.1%, 9.2% and 6.4% for formoterol, salmeterol and placebo, respectively; this was statistically significantly larger after formoterol than salmeterol (p = 0.008) or placebo (p < 0.001). All treatments were well tolerated.

CONCLUSION

In COPD patients, formoterol 9 μg has an onset of bronchodilatory effect that is more rapid than salmeterol 50 μg based on FEV₁ at 5 minutes post-dose.

CLINICAL TRIAL REGISTRATION

Clinicaltrials.gov identifier: NCT01048333; AstraZeneca study code: D5127C00001.

摘要

背景

支气管扩张剂疗法是慢性阻塞性肺疾病（COPD）症状管理的核心，对于轻度 COPD 患者推荐使用短效支气管扩张剂治疗。

目的

本研究旨在评估中重度 COPD 患者单次应用福莫特罗 9μg 与沙美特罗 50μg 的起效时间。

方法

这是一项多中心、双盲、双模拟、安慰剂对照的三交叉、单次剂量研究，纳入≥40 岁的中重度 COPD 患者，随机接受福莫特罗 9μg 经 Turbuhaler® 吸入装置给药+安慰剂经 Diskus® 吸入装置给药、沙美特罗 50μg 经 Diskus® 吸入装置给药+安慰剂经 Turbuhaler® 吸入装置给药或安慰剂经 Turbuhaler® 和 Diskus® 给药（洗脱期 2-7 天）。研究全程使用特布他林 0.5mg/吸经 Turbuhaler® 作为缓解药物。主要终点为单次给药后 5 分钟时的第 1 秒用力呼气量（FEV₁）。次要终点包括单次给药后 5 分钟时 FEV₁ 增加≥12%的患者比例。

结果

109 名患者被随机分组，108 名患者完成了研究。与基线相比，福莫特罗、沙美特罗和安慰剂给药后 5 分钟时的 FEV₁ 增加值分别为 7.2%、4.1%和 0.7%，福莫特罗的增加显著大于沙美特罗（治疗效果比值：1.030；95%置信区间 1.008，1.052；p=0.009），福莫特罗与安慰剂（1.064；95%置信区间 1.041，1.087；p<0.001），沙美特罗与安慰剂（1.033；95%置信区间 1.011，1.056；p=0.003）。福莫特罗、沙美特罗和安慰剂给药后 5 分钟时 FEV₁ 增加≥12%的患者比例分别为 23.1%、9.2%和 6.4%；福莫特罗显著大于沙美特罗（p=0.008）或安慰剂（p<0.001）。所有治疗均耐受良好。