Effects of Dual Bronchodilator Treatment (Tiotropium + Olodaterol Respimat) on Cardiopulmonary Interactions in Hyperinflated Patients With COPD
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Blood Flow Index (BFI)
研究概览
简要总结
The deleterious consequences of lung hyperinflation seem not to be restricted to the respiratory system in patients with chronic obstructive pulmonary disease (COPD). Cardiac function, in particular, is strongly influenced by changes in lung volumes and intra-thoracic pressures. In this context, strategies to reduce lung hyperinflation and the work of breathing can positively impact upon cardiac output and blood flow redistribution to peripheral muscles in these patients. There is growing evidence that combination of bronchodilators of different classes is an efficacious and safe strategy for further improving airflow obstruction and hyperinflation in patients with more advanced COPD. Therefore, we aim to investigate that, compared with placebo, a novel LABA/LAMA fixed combination (tiotropium 5 mcg plus olodaterol 5 mcg via Respimat® (Inspiolto®) (TIO/OLO) would decrease lung volumes at rest and during exercise, thereby improving: 1) central and peripheral hemodynamics and 2) arterial oxygenation, with positive consequences on skeletal muscle oxygenation and exercise tolerance in hyperinflated patients with moderate to very severe COPD.
详细描述
Prospective, proof-of-concept, single-dose study will be conducted using a randomized, double-blind, placebo-controlled, crossover design. Treatment will consist of a single dose of tiotropium 5mcg and olodaterol 5mcg via Respimat (Inspiolto)(TIO/OLO) or placebo; the order of treatment will be randomized. Submaximal cardiopulmonary exercise tests will be performed 1 hour after inhalation of TIO/OLO or placebo. Changes in blood flow index (BFI) measured by near-infrared spectroscopy (NIRS) during exercise will be the primary study endpoint.
Written informed consent will be obtained from all participants prior to performing any study related procedures. Participants will complete: 1) an initial visit to determine eligibility for the study; 2) a run-in visit conducted after 2 weeks of stabilization on short-acting bronchodilator therapy to familiarize subjects with the standardized exercise test (submaximal cardiopulmonary exercise tests) to be used in the subsequent treatment visits; and 3) two treatment visits, randomized to order, conducted 3-7 days apart.
Visit 1 will include:
- A thorough medical history;
- Clinical assessment;
- Chronic activity-related dyspnea evaluation;
- Complete pulmonary function testing;
- A symptom-limited incremental exercise test on a cycle ergometer to determine maximal exercise capacity (Wmax); and
- Post-salbutamol pulmonary function testing for assessment of bronchodilator responsiveness.
Visit 2 will consist of discontinuous submaximal cardiopulmonary exercise testing for familiarization.
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, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥50 years;
- •Male or female gender;
- •Long-term history of active smoking;
- •Signs and symptoms of COPD with adequate treatment according to the GOLD recommendations for at least 3 months (1);
- •A modified MRC dyspnea score ≥2 or a Baseline Dyspnea Index ≤8;
- •Resting lung hyperinflation as demonstrated by inspiratory capacity <80% predicted or functional residual capacity >120% predicted at Visit 1;
- •Objective evidence of dynamic hyperinflation (a decrease in inspiratory capacity from rest >200 mL)(24,25) and peak exercise dyspnea (breathing discomfort) ≥ leg discomfort scores during the incremental cardiopulmonary exercise test at Visit 1;
- •A positive "volume" response (≥200 mL increase in inspiratory capacity) to a bronchodilator (400μg salbutamol) at Visit 1
- •Ability to perform all study procedures and provide/sign informed consent.
排除标准
- •Asthma or other concomitant pulmonary disease;
- •Use of oral steroids in the preceding month;
- •Orthopedic/rheumatological limitation precluded cycling;
- •Type I or non-controlled type II diabetes mellitus or other endocrine diseases;
- •Unstable angina, life-threatening cardiac arrhythmias, use of an implantable defibrillator;
- •Myocardial infarction within the previous 6 months;
- •History of long QT syndrome (or prolonged corrected QT interval (>450 ms during screening);
- •Clinically significant ECG abnormality;
- •History of exercise-induced syncope;
- •Any contraindication for exercise testing;
- •Inability to understand and cooperate with the procedures.
研究组 & 干预措施
Tiotropium + Olodaterol first
tiotropium 5 mcg plus olodaterol 5 mcg via Respimat® single dose in Visit 3 followed by PLACEBO via Respimat® single dose in Visit 4
干预措施: Tiotropium + Olodaterol (Drug)
Tiotropium + Olodaterol first
tiotropium 5 mcg plus olodaterol 5 mcg via Respimat® single dose in Visit 3 followed by PLACEBO via Respimat® single dose in Visit 4
干预措施: PLACEBO (Other)
PLACEBO FIRST
Placebo via Respimat® single dose in Visit 3 followed bytiotropium 5 mcg plus olodaterol 5 mcg via Respimat® single dose in Visit 4
干预措施: Tiotropium + Olodaterol (Drug)
PLACEBO FIRST
Placebo via Respimat® single dose in Visit 3 followed bytiotropium 5 mcg plus olodaterol 5 mcg via Respimat® single dose in Visit 4
干预措施: PLACEBO (Other)
结局指标
主要结局
Blood Flow Index (BFI)
时间窗: 1 day
Near infrared spectroscopy (NIRS)-derived muscle ICG difference divided by the rise time from 10 to 90% of peak.
次要结局
- Inspiratory reserve volume(1 day)
- Inspiratory capacity(1 day)
- Cardiac output(1 day)
- Tlim(1 day)
- Exercise dyspnea(1 day)
- Muscle oxygenation(1 day)
研究者
Dr. J. Alberto Neder
Clinical professor
Queen's University