Clinical trial NCT01693003: Indacaterol Versus Tiotropium on Dynamic Hyperinflation in COPD
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
Lead sponsor: Irmandade Santa Casa de Misericórdia de Porto Alegre
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2012-09-26
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Exercise tolerance
timeFrame: 3 weeks
Secondary outcomes:
measure: Effort-related dyspnea during daily activities
timeFrame: 3 weeks
measure: Airway diameter and volume, and extension of pulmonary emphysema by multidetector helical chest computed tomography
timeFrame: 3 weeks
measure: Oxidative stress before and after exercise tests
timeFrame: 3 weeks
measure: Exercise dyspnea
timeFrame: 3 weeks
measure: Dynamic pulmonary hyperinflation
timeFrame: 3 weeks
Other outcomes:
measure: Adverse events
timeFrame: Participants will register adverse events in clinical research diaries or communicate to investigator during 3-week treatment period
Locations:
city: Porto Alegre
country: Brazil
facility: Pavilhão Pereira Filho
state: Rio Grande do Sul
city: Porto Alegre
country: Brazil
facility: Pavilhão Pereira Filho
state: RS
Study officials:
affiliation: Santa Casa de Porto Alegre
name: Paulo Z Teixeira, MD
role: STUDY_CHAIR
References:
citation: Berton DC, Santos AH, Bohn I Jr, Lima RQ, Breda V, Teixeira PJ. Effects of indacaterol versus tiotropium on exercise tolerance in patients with moderate COPD: a pilot randomized crossover study. J Bras Pneumol. 2016 Sep-Oct;42(5):367-373. doi: 10.1590/S1806-37562015000000334.