Modification of Disease Outcome in COPD. Shortterm Versus Longterm Treatment With Inhaled Corticosteroids, Either or Not Combined With a Long-Acting Beta2-Agonist.
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 200
- 试验地点
- 4
- 主要终点
- Inflammation: localisation, numbers and profile of neutrophils, eosinophils, macrophages, and CD8+T cells in bronchial biopsy specimens after 6 months and 2.5 years treatment.
研究概览
简要总结
The hypothesis to be tested of this study is that treatment with fluticasone propionate leads to an initial improvement in symptoms, quality of life and lungfunction and a reduction in airways hyperresponsiveness. The continued decline of lungfunction in COPD may not be influenced by longer lasting treatment. Addition of salmeterol will augment the initial benefits of fluticasone without changing the longterm decline in lungfunction.
详细描述
Aim The primary aim of this study was to investigate whether short-term treatment with inhaled corticosteroids in COPD results in greater improvements in airway pathology, thereby leading to larger clinical benefits, than continuous long-term treatment. To that end, the outcome variables included features of airways inflammation and remodelling as well as clinical symptoms, exacerbations, quality of life, decline in FEV1, bronchial responsiveness, and pharmaco-economics. The secondary aim of the study was to examine the histopathological and clinical benefits of the combined treatment with an inhaled steroid and a long-acting ß2-agonist in COPD.
Methods Patients. Patients with COPD (45-75 yr, >10 pckyr) not using inhaled steroids for the past 3 months were recruited.
Design. In a prospective, longitudinal, double blind, 4-arm study, the patients were followed during 2.5 years (Figure 1). They were treated with high dose inhaled corticosteroids (500 g fluticasone bid), combined inhaled steroids+long-acting ß2-agonist (500 µg fluticasone+50 µg salmeterol) or placebo for 6 months. Half of the patients in the steroid group continued their treatment with steroids for another 2 years, whereas the other half received placebo. The combination therapy and placebo groups remained unaltered treatment up to 2.5 years.
Measurements. Symptoms, exacerbations, QOL questionnaires and spirometry were monitored every 3 months. Peripheral blood eosinophils, IgE, exhaled NO, bodyplethysmography, CO-diffusion capacity, PC20 methacholine, sputum induction and bronchoscopy were performed at 0, 6, and 30 months. In BAL and induced sputum we are measuring cell differentials and their state of activation. Immunohistochemistry is being performed in bronchial biopsy specimens, staining for markers on infiltrative and resident cells, and morphometric analysis will allow airway remodelling to be quantified, by using a computerized image analysis system. The effects of treatment will be analyzed by relating the observed changes in clinical and pathophysiological outcome, to those in cellular and histological outcome by using linear mixed statistical models.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double
入排标准
- 年龄范围
- 45 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •COPD patients with > 10 pack years.
- •Written informed consent.
- •Able to complete a diary card.
- •At least one of the following symptoms: chronic cough, chronic sputum production, frequent exacerbations, or dyspnoea at exertion.
- •Postbronchodilator FEV1 below 90% confidence interval of predicted and postbronchodilator FEV1/FVC below 90% confidence interval of predicted.
排除标准
- •No oral corticosteroids 3 months prior to the study or maintenance treatment with corticostroids 6 months prior to the study.
- •No history of asthma, lung diseases other than COPD, other diseases likely to interfere with the study.
结局指标
主要结局
Inflammation: localisation, numbers and profile of neutrophils, eosinophils, macrophages, and CD8+T cells in bronchial biopsy specimens after 6 months and 2.5 years treatment.
次要结局
- Clinical: symptoms, exacerbations, quality of life, lung function, 6 min walking test. Inflammation: markers in sputum and BAL, profile of epithelial cells, remodeling.