Indacaterol Versus Tiotropium on Dynamic Hyperinflation in COPD

Study Overview
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Brief Summary
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Exercise intolerance is a major complain of patients with chronic obstructive pulmonary disease (COPD). Dynamic hyperinflation has been recognized as an important limiting factor responsible for the appearance of intolerable dyspnea during exercise. Regular treatment with long-acting bronchodilators promotes a more sustained reduction of hyperinflation and consequent symptom relief and increase in the patient's ability to overcome physical demands of daily life. Tiotropium bromide (TIO) is a new generation, long-acting anticholinergic bronchodilator that significantly improves lung function, reduces symptoms and improves exercise tolerance in patients with advanced COPD. Indacaterol is a new ultra-long duration (>24 h) β2-agonist, which promotes sustained dilation of the bronchi with a once-daily administration. Compared to tiotropium, indacaterol provides evidence that is as effective as tiotropium for bronchodilation, as well as other clinical outcomes such as dyspnea and state of health. However, comparative effects of indacaterol versus tiotropium with regard to outcomes in tolerance, dyspnea and dynamic lung hyperinflation during exercise is scarce. We hypothesized that indacaterol and TIO are not different in terms of exercise tolerance and its determinants (dynamic hyperinflation and dyspnea).

Official Title
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Randomized, Open-label, Crossover Clinical Trial to Assess the Effects of Indacaterol 150 µg d.o. Compared to Tiotropium Bromide 5 µg d.o. on Dyspnea, Dynamic Pulmonary Hyperinflation and Exercise Tolerance in Patients With Moderate COPD

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Indacaterol
* Drug: Tiotropium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women (neither pregnant nor nursing women) ≥40 years of age, with a history of smoking (>20 years/pack) and COPD diagnosis according to GOLD criteria. Post-bronchodilator FEV1 >50% and <80%, and FEV1/FVC ≤70% of predicted value. Exclusion Criteria: Hospital admission due to COPD exacerbation or lung infection in the 6 weeks prior to screening, diagnosis of current or previous bronchial asthma, history of allergic rhinitis or other atopic diseases, or peripheral eosinophilia >400/mm3. Inability to discontinue the usual bronchodilator therapy prior to initial screening tests, need for continuous oxygen therapy, or arterial oxygen saturation <85% at rest, or history of adverse reactions to sympathomimetic amines or use of inhaled medication. Anemia, hypo- or hyperthyroidism, hyperadrenergic conditions, uncontrolled insulin-dependent diabetes mellitus, malignancy, or any disease or condition that limits exercise capacity other than COPD. History of drug or alcohol abuse, poor adherence to drug treatment, or treatment with any investigational drug in the month before screening. Patients with ventricular arrhythmia. Patients with <80% oxyhemoglobin saturation during exercise testing

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Indacaterol first<br>Indacaterol 150 µg d.o. during the first 3-week period followed by other 3-week period of tiotropium bromide 5 µg d.o. separated by a wash-out phase of at least 5 to 14 days between each treatment period | Drug: Indacaterol<br>* 150 µg d.o. during the first 3 weeks<br>* Other names: Onbrez Breezhaler®;Drug: Tiotropium<br>* 150 µg d.o. during 3 weeks<br>* Other names: Spiriva Respimat®;|
| Experimental: Tiotropium first<br>Tiotropium bromide 5 µg d.o. during the first 3-week period followed by other 3-week period of Indacaterol 150 µg d.o. separated by a wash-out phase of at least 5 to 14 days between each treatment period | Drug: Indacaterol<br>* 150 µg d.o. during the first 3 weeks<br>* Other names: Onbrez Breezhaler®;Drug: Tiotropium<br>* 150 µg d.o. during 3 weeks<br>* Other names: Spiriva Respimat®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise tolerance | Time between beginning of high intensity constant load (75-85% of the peak achieved in a previous cycloergometer incremental test) cardiopulmonary exercise test and point at which patient cannot tolerate the effort any longer. | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effort-related dyspnea during daily activities |  | 3 weeks | 
| Airway diameter and volume, and extension of pulmonary emphysema by multidetector helical chest computed tomography |  | 3 weeks | 
| Oxidative stress before and after exercise tests |  | 3 weeks | 
| Exercise dyspnea | Dyspnea evaluated by Borg scale each 2 minutes during high intensity constant load cardiopulmonary exercise test until exhaustion (peak exercise) | 3 weeks | 
| Dynamic pulmonary hyperinflation | Inspiratory capacity measured each 2 minutes during high intensity constant load cardiopulmonary exercise test until exhaustion (peak exercise). | 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD