The Treatment Effect of Inhaled Corticosteroid and Long-acting beta2 Agonist Combination Versus Long-acting Anti-cholinergic Agent on Stratified COPD Patients Based on the Levels of Exhaled Nitric Oxide
试验速览
- 阶段
- 4 期
- 入组人数
- 143
- 试验地点
- 1
- 主要终点
- Changes of eNO level
研究概览
简要总结
It is recognized that eosinophilic airway inflammation is more likely respond to steroid treatment. However, in real-world practice, it is difficult to routinely assess airway inflammation using sputum induction because of technical and facility requirement. COPD (chronic obstructive pulmonary disease) is a heterogeneous disease and it remains a great challenge to identify patients who have eosinophilic airway inflammation and respond to steroid treatment well. A recent study demonstrated elevated plasma D-dimer was associated with acute inflammation and a significant predictor of pulmonary embolism in COPD exacerbated patients. D-dimer may potentially act as a marker of inflammation and a predictor of cardiovascular event in COPD patients. The investigators preliminary study demonstrated that exhaled nitric oxide (eNO) > 23.5 ppb is a good surrogate marker to predict eosinophilic airway inflammation in COPD patients who were newly diagnosed or untreated for at least 3 months. There were significant correlations among sputum eosinophils, eNO and serum total immunoglobulin E (IgE). Particularly, eNO predicted sputum eosinophilia (> 3%) in COPD at a sensitivity and specificity of 62% and 71% respectively. Herein, the investigators test the hypothesis that eNO may act as a biomarker to determine treatment option for COPD.
详细描述
Eligible COPD patients (newly diagnosed or untreated for at least 3 months) will be enrolled at out-patient clinic after consenting by participants. Upon enrollment, exhaled NO (eNO) will be measured and patients will be categorized into 2 groups according to eNO levels: either high exhaled NO (greater than or equal to 23.5 ppb) or low eNO (< 23.5 ppb) group. In each group, patients will be randomized to receive either 2 inhalations of fluticasone/salmeterol 250/25 mcg/ pudd twice daily or 2 inhalations of tiotropium 2.5 mcg/inhalation for 12 weeks and followed at scheduled visits. Testing outcome measures include eNO, lung function, different count and mediators in induced sputum, and which will be tested as the following timings: before (baseline, week 0), and after treatment (week 4 and week 12). Rescue medication and drug compliance will be record.
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
- None
入排标准
- 年龄范围
- 40 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female outpatients aged from 40 to 90 years
- •Current or ex-smoker, with smoking history ≧ 20 pack- years
- •Newly diagnosed or untreated (at least 3 months) COPD patients (forced expiratory volume in first second (FEV1)/forced vital capacity (FVC) < 70%) with post-bronchodilator FEV1 < 80 % predicted value.
排除标准
- •Concurrent allergic rhinitis, eczema, and asthma.
- •Clinically overt bronchiectasis, lung cancer, active tuberculosis, or other known specific pulmonary disease.
- •A chest X-ray indicating diagnosis other than COPD that might interfere with the study.
- •Major disease abnormalities are uncontrolled on therapy.
- •Alcohol or medication abuse.
- •Patients had lower respiratory tract infections or received systemic steroid in the 4 weeks prior to the commencement of study.
- •Women with childbearing potential during the period of trial.
- •Unable or unwilling to comply with all protocol
研究组 & 干预措施
high eNO: ICS/LABA
patients with eNO >=23.5 ppb, receive inhaled corticosteroid (ICS)/long-acting beta2 agonist (ICS/LABA) of fluticasone/salmeterol 250/25 mcg/puff, 2 puffs bid.
干预措施: fluticasone/salmeterol, tiotropium (Drug)
high eNO: LAMA
patients with eNO >=23.5 ppb, receive long acting muscarinic antagonist (LAMA) of tiotropium 2 inhalations 2.5 mcg/inhalation, once daily
干预措施: fluticasone/salmeterol, tiotropium (Drug)
Low eNO: ICS/LABA
patients with eNO < 23.5 ppb, receive fluticasone/salmeterol 250/25 mcg/puff, 2 puffs bid
干预措施: fluticasone/salmeterol, tiotropium (Drug)
Low eNO: LAMA
patients with eNO < 23.5 ppb, receive tiotropium 2 inhalations 2.5 mcg/inhalation, once daily
干预措施: fluticasone/salmeterol, tiotropium (Drug)
结局指标
主要结局
Changes of eNO level
时间窗: Changes of eNO level (ppb) from baseline at 12 weeks
次要结局
- Changes of lung function parameters (FEV1, FVC)(Changes of lung function parameters (FEV1, FVC) from baseline at 12 weeks)
- Changes of serum level of IgE(Changes of serum level of IgE (IU/ml) from baseline at 12 weeks)
- Changes of serum level of matrix metalloproteinase (MMP)-9(Changes of serum level of MMP-9 (ng/ml) from baseline at 12 weeks)
- Changes of serum level of D-dimer(Changes of serum level of D-dimer (ug/ml) from baseline at 12 weeks)
- Changes of scales of life quality questionnaire(Changes of scales of life quality questionnaire from baseline at 12 weeks)
- Changes of proportion of cell counts in induced sputum(Changes of proportion of cell counts in induced sputum from baseline at 12 weeks)
- Changes of MMP-9 level in induced sputum(Changes of MMP-9 levle (ug/ml) in induced sputum from baseline at 12 weeks)