Acute Effect of Aclidinium on Hyperinflation and Lung Volume Distribution in Severe COPD Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Residual Volume Variation from baseline
研究概览
简要总结
- Chronic Obstructive Pulmonary Disease (COPD) is characterized by lung hyperinflation and flow limitation. These physiopathological modifications are secondary to loss of elastic recoil and bronchial obstruction due to emphysema.
- The cornerstone of COPD treatment is represented by inhaled beta-2 agonists and anticholinergics. The molecules of the latter classes can be characterized by short lasting action (few hours), long acting action (12 hours) or ultra long acting duration of action (24 hours).
- For years the only anticholinergic (or antimuscarinic) drug other than those used by aerosol, was Tiotropium Bromide. Recently two new antimuscarinic agents have been launched on the market: glycopyrronium bromide (once daily) and aclidinium (twice daily).
- The Single Breath Nitrogen Test is capable of identifying the pulmonary closing volume. The part of the curve that reflects lung ventilation inhomogeneity is the slope of phase III
- For COPD patients, the most important characteristic for an inhalatory drug is a prompt action in order to give a quick relief from respiratory symptoms, in particular dyspnoea.
- The objective of this study is to study the acute action of glycopyrronium and aclidinium in terms of reduction of hyperinflation, pulmonary specific resistances, lung volume distribution and dyspnoea at rest in severe COPD patients.
- To our knowledge no study has explored these aspects before.
详细描述
Chronic Obstructive Pulmonary Disease (COPD) is a disease characterized by progressive and evolutionary physiopathological changes that are responsible for the developing of respiratory symptoms, disability, poor quality of life and morbidity. These changes are secondary to parenchymal disruption and chronic bronchiolar inflammation in major part due to cigarette smoke.
Lung architectural derangement and loss of elastic recoil secondary to emphysema together with decreased internal bronchiolar lumen due to mucosal chronic inflammation are responsible for bronchial obstruction, flow limitation and lung hyperinflation. All these features bring to exertional dyspnoea, chronic cough and sputum and so decreased activeness in daily life activities.
The Single Breath Nitrogen Washout Test (SBN2) is one of the test that more adequately can catch the modifications of small airways and their premature collapse called closing volume (CV). Together with CV the test reflects pulmonary ventilation inhomogeneity through the slope of the so called phase III (a plateau line of nitrogen concentration that is steeper the bigger the ventilation inhomogeneity). In literature the effects of COPD inhalatory treatments on this modifications and on hyperinflation were until today poorly analysed. Recently some new anticholinergic molecules were developed, in particular Aclidinium Bromide and Glycopyrronium Bromide, and there is no trace of such evaluation in medical literature with those new inhalatory drugs.
The study of the acute effects of these drugs on lung mechanics are mandatory because the quicker the effects, the faster the patient's dyspnoea relief.
The study will comprise a first enrollment visit and then the suitable subjects will undergo a pharmacological washout of 72 hours from any inhalatory drug except from Salbutamol.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signature of informed consent
- •COPD patients with age raging from 50 to 85 years old
- •Patients with at least a history of COPD of one year
- •COPD patients clinically stable in the last three months
- •COPD subjects with Forced Expiratory Volume at one second (FEV1)<50% of predicted value
- •COPD subjects with Residual Volume (RV) >125% predicted value
- •FEV1/Forced Vital Capacity (FVC) <88% (males) or <89% (females) of Low Levels of Normality (LLN)
- •COPD former or active smokers with at least a smoking history of 20 pack year
排除标准
- •Acute Bronchial Exacerbation at recruitment
- •Fertile women with age between 18 and 50 years old or with active period
- •Pregnancy
- •Subjects enrolled in other clinical trials or that have taken part in one of them in the month preceding the enrollment.
- •FEV1/FVC more than 70% of predicted value in basal conditions
- •FEV1 more than 70% of predicted value in basal conditions
- •Known deficit of alpha 1 antitrypsin
- •Subjects that underwent a Lung Volume Reduction Surgery (LVRS)
- •Subjects with known positivity to Human Immunodeficiency Virus (HIV)
- •Misuse of alcool or drugs
- •Lack of compliance in performing respiratory tests
- •Subjects not capable to follow the study prescriptions because of psychic disorders or language problems.
- •Long Term Oxygen Therapy with flows > 6 litres per minute (l/min) at rest
研究组 & 干预措施
Aclidinium - Glycopyrronium
Patients will assume Aclidinium Bromide 322 dry powder by Genuair inhaler and Glycopyrronium 44 dry powder inhaler by Breezehaler inhaler (placebo) after 72 hours from inhalatory therapy washout (only short acting bronchodilators permitted). Then, after 72 hours of inhalatory drugs washout (only short acting bronchodilators permitted), they will receive Glycopyrronium Bromide 322 mcg via Breezehaler inhaler and Aclidinium Bromide 322 dry powder by Genuair inhaler (placebo).
干预措施: Aclidinium Bromide (Drug)
Aclidinium - Glycopyrronium
Patients will assume Aclidinium Bromide 322 dry powder by Genuair inhaler and Glycopyrronium 44 dry powder inhaler by Breezehaler inhaler (placebo) after 72 hours from inhalatory therapy washout (only short acting bronchodilators permitted). Then, after 72 hours of inhalatory drugs washout (only short acting bronchodilators permitted), they will receive Glycopyrronium Bromide 322 mcg via Breezehaler inhaler and Aclidinium Bromide 322 dry powder by Genuair inhaler (placebo).
干预措施: Glycopyrronium Bromide (Drug)
Glycopyrronium - Aclidinium
Patients will assume Glycopyrronium Bromide 44 mcg dry powder by Breezehaler inhaler and Aclidinium Bromide 322 dry powder by Genuair inhaler (placebo) after 72 hours of inhalatory therapy washout (only short acting bronchodilators permitted). Then, after 72 hours of inhalatory drugs washout (only short acting bronchodilators permitted) they will receive Aclidinium Bromide 322 mcg via Genuair inhaler and Glycopyrronium Bromide 44 mcg dry powder by Breezehaler inhaler (placebo).
干预措施: Aclidinium Bromide (Drug)
Glycopyrronium - Aclidinium
Patients will assume Glycopyrronium Bromide 44 mcg dry powder by Breezehaler inhaler and Aclidinium Bromide 322 dry powder by Genuair inhaler (placebo) after 72 hours of inhalatory therapy washout (only short acting bronchodilators permitted). Then, after 72 hours of inhalatory drugs washout (only short acting bronchodilators permitted) they will receive Aclidinium Bromide 322 mcg via Genuair inhaler and Glycopyrronium Bromide 44 mcg dry powder by Breezehaler inhaler (placebo).
干预措施: Glycopyrronium Bromide (Drug)
结局指标
主要结局
Residual Volume Variation from baseline
时间窗: At baseline, 5, 15, 30, 60 and 180 minutes after study drug administration
Residual Volume is obtained by performing body plethysmography before study drug inhalation (baseline), and again 5, 15, 30,60 and 180 minutes after inhalation of study drug. The same subject will undergo the same evaluation in the second part of the study, after the crossing over
Functional Residual Capacity variation from baseline
时间窗: At baseline, 5, 15, 30, 60 and 180 minutes after study drug administration
Functional Residual Capacity (plethysmographic Intra Thoracic Gas Volume - ITGV) is obtained by performing body plethysmography before study drug inhalation (baseline), and again 5, 15, 30,60 and 180 minutes after inhalation of study drug. The same subject will undergo the same evaluation in the second part of the study, after the crossing over
次要结局
- Phase III slope variation from baseline(At baseline, 5, 15, 30, 60 and 180 minutes after study drug administration)
- Oxygen and Carbon Dioxide variation from baseline(At baseline and 180 minutes after inhalation of study drug)
- Visual Analogical Scale (VAS) for Dyspnoea at rest variation from baseline(At baseline, 5, 15, 30, 60 and 180 minutes after study drug administration)
研究者
Pierachille Santus
Head of Pulmonary Rehabilitation Unit
University of Milan