Indacaterol Versus Tiotropium on Dynamic Hyperinflation in COPD

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

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).

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Indacaterol; Drug: Tiotropium

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • RS
    • Porto Alegre, RS, Brazil
      • Pavilhão Pereira Filho
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90002-090
      • Pavilhão Pereira Filho

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Indacaterol first; 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; 150 µg d.o. during the first 3 weeks; Other Names: Onbrez Breezhaler®; Drug: Tiotropium; 150 µg d.o. during 3 weeks; Other Names: Spiriva Respimat®
Experimental: Tiotropium first; 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; 150 µg d.o. during the first 3 weeks; Other Names: Onbrez Breezhaler®; Drug: Tiotropium; 150 µg d.o. during 3 weeks; Other Names: Spiriva Respimat®

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Adverse events, including serious adverse events, will be collected and reported in the CRF (Clinical Research File) of the study. Adverse event is any sign, symptom or undesired medical condition that occurs after the beginning of the study even if said event is not considered related to the drug (or therapy) of study. Information on adverse events either reported voluntarily by the patient, identified through questioning by the investigator, or detected by physical examination, laboratory testing or otherwise, will be collected and recorded.	Participants will register adverse events in clinical research diaries or communicate to investigator during 3-week treatment period

Collaborators and Investigators

• Sponsor: Irmandade Santa Casa de Misericórdia de Porto Alegre
• Collaborators: Novartis
• Investigators: Study Chair: Paulo Z Teixeira, MD, Santa Casa de Misericordia de Porto Alegre

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: September 19, 2012
• First Submitted That Met QC Criteria: September 25, 2012
• First Posted (Estimate): September 26, 2012

Study Record Updates

• Last Update Posted (Estimate): January 8, 2014
• Last Update Submitted That Met QC Criteria: January 6, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide
• Other Study ID Numbers: ISCMPALABAtrial