Effect of Tiotropium (Spiriva) on Exercise Tolerance in COPD Patients

Study Overview
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Brief Summary
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To investigate whether tiotropium (Spiriva) improves exercise endurance in patients with COPD

Official Title
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Effect of Tiotropium on Exercise Tolerance and Static and Dynamic Lung Volumes in COPD Patients (A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: tiotropium bromide


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female patients with a clinical diagnosis of Chronic Obstructive Pulmonary Disease (COPD) based on American Thoracic Society (ATS) guidelines with: Relatively stable, moderate to severe airway obstruction with an Forced Expiratory Volume in One Second (FEV1) less than or equal to 65% of predicted normal (determined at Visit 1). Presence of lung hyperinflation as demonstrated by Functional Residual Capacity determined by body plethysmography (TGV(FRC)) greater than or equal to 120% of predicted normal (determined at Visit 1). Age greater or equal to 40 years and less than or equal to 75 years. A cigarette smoking history of more than ten pack-years. A pack-year was defined as the equivalent of smoking one pack of cigarettes per day for a year. Able to perform all specified procedures and able to maintain all necessary records during the study period as required in the protocol. Able to inhale the trial medication from the HandiHaler device. Exclusion criteria: Patients with a significant disease other than COPD. A significant disease was defined as a disease which, in the opinion of the investigator, may have put the patient at risk because of participation in the trial or may have influenced the results of the trial or the patient's ability to participate in the trial. Patients with clinically significant abnormal baseline hematology, blood chemistry or urinalysis. If the abnormality defined a disease listed as an exclusion criterion, the patient was excluded. Patients with Serum Glutamic Oxaloacetic Transaminase (SGOT) ≥1.5 x ULN (upper limit of normal range), Serum Glutamic Pyruvic Transaminase (SGPT) ≥1.5 x ULN bilirubin ≥1.5 x ULN or creatinine ≥1.5 x ULN were excluded regardless of the clinical condition. Patients with a recent history (i.e., 1 year or less) of myocardial infarction. Patients with a recent history (i.e., 3 years or less) of heart failure, pulmonary edema, or patients with cardiac arrhythmia (with or without symptoms) or any contraindication to exercise. Patients requiring the regular use of daytime oxygen therapy. Patients with known active tuberculosis. Patients with a history of cancer within the last 5 years. Patients with treated basal cell carcinoma were eligible. Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis. Patients who had undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons were evaluated as per the first exclusion criterion (i.e., significant disease other than COPD). Patients with an upper respiratory tract infection in the 6 weeks prior to the Screening Visit (Visit 1) or during the run-in period. Further exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: tiotropium bromide|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endurance time during a constant work rate exercise test to symptom limitation |  | 2 hours and 15 minutes after trial medication administration on Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Constant work rate exercise test to symptom limitation |  | 8 hours post-dose after 6 weeks of treatment | 
| Breathing discomfort during constant work rate exercise test as measured by the modified Borg Scale |  | 6 weeks | 
| Dynamic lung hyperinflation during exercise as determined by IRVdyn (IC minus VT) and EELVdyn (TLC) |  | 6 weeks | 
| Evaluation of VE and VEcap during exercise (selected centers) |  | 6 weeks | 
| Evaluation of static lung hyperinflation as measured by RV/TLC and by TGV(FRC)/TLC |  | 6 weeks | 
| Evaluation of TAC (TAV = TLC(BOX)-VA(IG)) |  | 6 weeks | 
| Evaluation of slow vital capacity (SVC) |  | 6 weeks | 
| Evaluation of maximal expiratory flow rates and volumes FEV1, FVC, FEF25-75%, FEF50%, FEF75%, SVC |  | 6 weeks | 
| Evaluation of TGV, Raw, SGaw and RV |  | 6 weeks | 
| Evaluation of SaO2, VO2, VCO2, Ti, Te, VE, VT, breathing frequency (f) during constant work rate exercise test |  | 6 weeks | 
| Physician's Global Assessment |  | 6 weeks | 
| Assessement of Pulse/heart rate and blood pressure in conjunction with spirometry and exercise |  | 6 weeks | 
| Changes in Physical examination and ECG |  | 6 weeks | 
| Occurrence of Adverse Events |  | 6 weeks |