The Effects of Inhaled Aclidinium Bromide/Formoterol Fumarate on Inspiratory Pleural Pressures in Smokers: a Randomized, Double-blind, Placebo-controlled, Cross-over Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Inspiratory pleural pressures at rest and throughout incremental exercise (cmH2O)
研究概览
简要总结
This short-term study aims to prove the potential cardio-protective physiological effect of inhaled aclidinium bromide/formoterol fumarate on inspiratory pleural pressures.
Smoking is associated with gas-trapping (hyperinflation), even in the absence of chronic obstructive pulmonary disease. Breathing in the presence of gas-trapping requires large negative inspiratory pleural pressures, which are transmitted to the surface of the heart and increase cardiac wall stress.
Inhaled aclidinium bromide and formoterol fumarate has been shown to reduce gas-trapping, but the impact on inspiratory pleural pressures and biomarkers of cardiac stress in smokers is unknown.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Matched placebo.
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
- •Current and former smokers with ≥20 pack-years of smoking history
- •Gas-trapping (residual volume >110% predicted)
排除标准
- •Physician-diagnosis of chronic obstructive pulmonary disease in the past 1 year and regular use of long-acting antimuscarinic (LAMA) and/or long-acting beta-agonist (LABA) (i.e., at least 30 consecutive days)
- •Physician-diagnosis of asthma in the past 5 years
- •Regular inhaled corticosteroid (ICS) use in the past 5 years (i.e., at least 30 consecutive days)
- •Physician-diagnosis of other lung diseases (sarcoidosis, tuberculosis, cystic fibrosis, pulmonary fibrosis, lung cancer), or long-term oxygen therapy
- •Respiratory tract infection within 4-weeks
- •Physician-diagnosis of arrhythmia, or significant valvular disease.
- •Physician-diagnosis of myocardial infarction, unstable angina or heart failure requiring unscheduled outpatient or emergency department visit within 6-months.
- •Arrhythmia or prolonged corrected QT (QTc) on electrocardiogram.
- •Inability to use study inhaler
- •Benign prostatic hypertrophy
- •Pregnancy
- •Allergy to the study treatment, salbutamol, lidocaine, or severe milk protein allergy (note: lactose intolerance is not an exclusion criteria)
- •Contraindications to anti-cholinergic, beta-agonist, or cardiopulmonary exercise testing with manometry
- •Inability to provide written informed consent
研究组 & 干预措施
Active arm
Aclidinium bromide/formoterol fumarate dihydrate 400 mcg/12 mcg Twice daily (once in the morning, once in the evening) 7-days
干预措施: Aclidinium bromide/formoterol fumarate dihydrate (Drug)
Placebo arm
Placebo Twice daily (once in the morning, once in the evening) 7-days
干预措施: Placebo (Drug)
结局指标
主要结局
Inspiratory pleural pressures at rest and throughout incremental exercise (cmH2O)
时间窗: After 7-days of active or placebo drug
Mean difference in inspiratory pleural pressure measured by esophageal manometry at rest and throughout incremental exercise
次要结局
- Resting and dynamic lung volumes (end-inspiratory/end-expiratory lung volume)(After 7-days of active or placebo drug)
- Effect modification by hypertension status (Joint National Committee criteria).(After 7-days of active or placebo drug)
- Resting and exercise-induced changes in plasma natriuretic peptide concentrations (plasma concentration)(After 7-days of active or placebo drug)
- Effect modification by gender (self-reported).(After 7-days of active or placebo drug)
- Effect modification by smoking status (self-reported).(After 7-days of active or placebo drug)
- Effect modification by hyperinflation severity (Residual lung volume).(After 7-days of active or placebo drug)
- Effect modification by spirometric chronic obstructive pulmonary disease (COPD) status (forced expired volume in 1 second-to-forced vital capacity ratio below 0.7).(After 7-days of active or placebo drug)
研究者
Benjamin McDonald Smith
Assistant professor
McGill University Health Centre/Research Institute of the McGill University Health Centre