Indacaterol Versus Tiotropium on Dynamic Hyperinflation in COPD

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Paulo J Z Teixeira, Irmandade Santa Casa de Misericórdia de Porto Alegre
ClinicalTrials.gov Identifier:
NCT01693003
First received: September 19, 2012
Last updated: January 6, 2014
Last verified: January 2014
  Purpose

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).


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: Indacaterol
Drug: Tiotropium
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Irmandade Santa Casa de Misericórdia de Porto Alegre:

Primary Outcome Measures:
  • Exercise tolerance [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Effort-related dyspnea during daily activities [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
  • Airway diameter and volume, and extension of pulmonary emphysema by multidetector helical chest computed tomography [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
  • Oxidative stress before and after exercise tests [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
  • Exercise dyspnea [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
    Dyspnea evaluated by Borg scale each 2 minutes during high intensity constant load cardiopulmonary exercise test until exhaustion (peak exercise)

  • Dynamic pulmonary hyperinflation [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
    Inspiratory capacity measured each 2 minutes during high intensity constant load cardiopulmonary exercise test until exhaustion (peak exercise).


Other Outcome Measures:
  • Adverse events [ Time Frame: Participants will register adverse events in clinical research diaries or communicate to investigator during 3-week treatment period ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 20
Study Start Date: March 2013
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Onbrez Breezhaler®
Drug: Tiotropium
150 µg d.o. during 3 weeks
Other Name: 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 Name: Onbrez Breezhaler®
Drug: Tiotropium
150 µg d.o. during 3 weeks
Other Name: Spiriva Respimat®

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01693003

Locations
Brazil
Pavilhão Pereira Filho
Porto Alegre, Rio Grande do Sul, Brazil, 90002-090
Pavilhão Pereira Filho
Porto Alegre, RS, Brazil
Sponsors and Collaborators
Irmandade Santa Casa de Misericórdia de Porto Alegre
Novartis
Investigators
Study Chair: Paulo Z Teixeira, MD Santa Casa de Misericórdia de Porto Alegre
  More Information

No publications provided

Responsible Party: Paulo J Z Teixeira, Clinical professor and chair of the study, Irmandade Santa Casa de Misericórdia de Porto Alegre
ClinicalTrials.gov Identifier: NCT01693003     History of Changes
Other Study ID Numbers: ISCMPALABAtrial
Study First Received: September 19, 2012
Last Updated: January 6, 2014
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by Irmandade Santa Casa de Misericórdia de Porto Alegre:
COPD

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Tiotropium
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014