Tiotropium In Exercise

Study Overview
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Brief Summary
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The objective of this study is to evaluate the effects on exercise duration of 96 weeks treatment with 18 mcg tiotropium (Spiriva HandiHaler) daily as compared to placebo, in patients with COPD.

Official Title
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A Randomized, Double-blind, Placebo-controlled Two-year Trial to Examine the Changes in Exercise Endurance and COPD Treated With Tiotropium Once Daily (EXACTT)

Conditions
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Pulmonary Disease, Chronic Obstructive, Exercise

Intervention / Treatment
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* Drug: tiotropium 18 mcg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria All patients must sign an informed consent Diagnosis of COPD with specific spirometric criteria (determined at study visits) Age >= 40 years Medical Research Council Dyspnoea score >= 2 Current or ex-smoker with a >= 10 pack-year smoking history Ability to exercise on treadmill Exclusion criteria Significant diseases other than COPD such as history of life-threatening pulmonary obstruction, thoracotomy with pulmonary resection, interstitial lung disease, CF, pulmonary thromboembolic disease, clinically evident bronchiectasis, active tuberculosis, or known moderate to severe renal impairment Clinical history of asthma Use of supplemental oxygen therapy Respiratory tract infection or COPD exacerbation in the 6 weeks prior to Visit 1 or during the washout period prior to Visit 3 (may randomize 6 weeks after recovery) Recent history (<= 12 months) of myocardial infarction Unstable or life-threatening cardiac arrhythmia Malignancy treated with radiation therapy or chemotherapy in the last 5 years Pregnant or nursing women Known hypersensitivity to anticholinergic drugs or any component of the study medications Participation in pulmonary or cardiac rehab program within 13 weeks of Visit 1 Estimated life expectancy < 2 years Symptomatic prostatic hyperplasia or bladder neck obstruction Known narrow-angle glaucoma Any condition that is contraindicated for exercise Orthopaedic, muscular, neurological or cardiac disease that would interfere with regular participation in aerobic exercise or with exercise testing Body mass index < 18 kg/m2 or >35 kg/m2 list truncated for space

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tiotropium 18mcg<br>Oral inhalation once daily of 18mcg tiotropium via handihaler | Drug: tiotropium 18 mcg<br>* Oral inhalation once daily of 18mcg tiotropium via handihaler<br>|
| Placebo Comparator: Placebo<br>Oral inhalation once daily of placebo matching tiotropium via handihaler | Drug: Placebo<br>* Oral inhalation of once-daily placebo matching tiotropium via handihaler<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90% Constant Work Rate (CWR) Treadmill Endurance Time at 96 Weeks - Double-Blind Phase | Efficacy was assessed by measuring the exercise duration during a treadmill exercise test. | baseline, 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90% Constant Work Rate (CWR) Treadmill Endurance Time at 8 Weeks - Double-Blind Phase | Efficacy was assessed by measuring the exercise duration during a treadmill exercise test. | baseline, 8 weeks | 
| 90% Constant Work Rate (CWR) Treadmill Endurance Time at 16 Weeks - Double-Blind Phase | Efficacy was assessed by measuring the exercise duration during a treadmill exercise test. | baseline, 16 weeks | 
| 90% Constant Work Rate (CWR) Treadmill Endurance Time at 32 Weeks - Double-Blind Phase | Efficacy was assessed by measuring the exercise duration during a treadmill exercise test. | baseline, 32 weeks | 
| 90% Constant Work Rate (CWR) Treadmill Endurance Time at 48 Weeks - Double-Blind Phase | Efficacy was assessed by measuring the exercise duration during a treadmill exercise test. | baseline, 48 weeks | 
| 90% Constant Work Rate (CWR) Treadmill Endurance Time at 64 Weeks - Double-Blind Phase | Efficacy was assessed by measuring the exercise duration during a treadmill exercise test. | baseline, 64 weeks | 
| 90% Constant Work Rate (CWR) Treadmill Endurance Time at 80 Weeks - Double-Blind Phase | Efficacy was assessed by measuring the exercise duration during a treadmill exercise test. | baseline, 80 weeks | 
| Pre-treatment Forced Expiratory Volume in 1 Second (FEV1) at 8 Weeks - Double-Blind Phase | FEV1 is the maximal amount of air you can forcefully exhale in one second. | baseline, 8 weeks | 
| Pre-treatment Forced Expiratory Volume in 1 Second (FEV1) at 16 Weeks - Double-Blind Phase | FEV1 is the maximal amount of air you can forcefully exhale in one second. | baseline, 16 weeks | 
| Pre-treatment Forced Expiratory Volume in 1 Second (FEV1) at 32 Weeks - Double-Blind Phase | FEV1 is the maximal amount of air you can forcefully exhale in one second. | baseline, 32 weeks | 
| Pre-treatment Forced Expiratory Volume in 1 Second (FEV1) at 48 Weeks - Double-Blind Phase | FEV1 is the maximal amount of air you can forcefully exhale in one second. | baseline, 48 weeks | 
| Pre-treatment Forced Expiratory Volume in 1 Second (FEV1) at 64 Weeks - Double-Blind Phase | FEV1 is the maximal amount of air you can forcefully exhale in one second. | baseline, 64 weeks | 
| Pre-treatment Forced Expiratory Volume in 1 Second (FEV1) at 80 Weeks - Double-Blind Phase | FEV1 is the maximal amount of air you can forcefully exhale in one second. | baseline, 80 weeks | 
| Pre-treatment Forced Expiratory Volume in 1 Second (FEV1) at 96 Weeks - Double-Blind Phase | FEV1 is the maximal amount of air you can forcefully exhale in one second. | baseline, 96 weeks | 
| Post-treatment Forced Expiratory Volume in 1 Second (FEV1) at 8 Weeks - Double-Blind Phase | FEV1 is the maximal amount of air you can forcefully exhale in one second. | baseline, 8 weeks | 
| Post-treatment Forced Expiratory Volume in 1 Second (FEV1) at 16 Weeks - Double-Blind Phase | FEV1 is the maximal amount of air you can forcefully exhale in one second. | baseline, 16 weeks | 
| Post-treatment Forced Expiratory Volume in 1 Second (FEV1) at 32 Weeks - Double-Blind Phase | FEV1 is the maximal amount of air you can forcefully exhale in one second. | baseline, 32 weeks | 
| Post-treatment Forced Expiratory Volume in 1 Second (FEV1) at 48 Weeks - Double-Blind Phase | FEV1 is the maximal amount of air you can forcefully exhale in one second. | baseline, 48 weeks | 
| Post-treatment Forced Expiratory Volume in 1 Second (FEV1) at 64 Weeks - Double-Blind Phase | FEV1 is the maximal amount of air you can forcefully exhale in one second. | baseline, 64 weeks | 
| Post-treatment Forced Expiratory Volume in 1 Second (FEV1) at 80 Weeks - Double-Blind Phase | FEV1 is the maximal amount of air you can forcefully exhale in one second. | baseline, 80 weeks | 
| Post-treatment Forced Expiratory Volume in 1 Second (FEV1) at 96 Weeks - Double-Blind Phase | FEV1 is the maximal amount of air you can forcefully exhale in one second. | baseline, 96 weeks | 
| Pre-treatment Forced Vital Capacity (FVC) at 8 Weeks - Double-Blind Phase | FVC is the volume of air that can be forcibly blown out after full inspiration. | baseline, 8 weeks | 
| Pre-treatment Forced Vital Capacity (FVC) at 16 Weeks - Double-Blind Phase | FVC is the volume of air that can be forcibly blown out after full inspiration. | baseline, 16 weeks | 
| Pre-treatment Forced Vital Capacity (FVC) at 32 Weeks - Double-Blind Phase | FVC is the volume of air that can be forcibly blown out after full inspiration. | baseline, 32 weeks | 
| Pre-treatment Forced Vital Capacity (FVC) at 48 Weeks - Double-Blind Phase | FVC is the volume of air that can be forcibly blown out after full inspiration. | baseline, 48 weeks | 
| Pre-treatment Forced Vital Capacity (FVC) at 64 Weeks - Double-Blind Phase | FVC is the volume of air that can be forcibly blown out after full inspiration. | baseline, 64 weeks | 
| Pre-treatment Forced Vital Capacity (FVC) at 80 Weeks - Double-Blind Phase | FVC is the volume of air that can be forcibly blown out after full inspiration. | baseline, 80 weeks | 
| Pre-treatment Forced Vital Capacity (FVC) at 96 Weeks - Double-Blind Phase | FVC is the volume of air that can be forcibly blown out after full inspiration. | baseline, 96 weeks | 
| Post-treatment Forced Vital Capacity (FVC) at 8 Weeks - Double-Blind Phase | FVC is the volume of air that can be forcibly blown out after full inspiration. | baseline, 8 weeks | 
| Post-treatment Forced Vital Capacity (FVC) at 16 Weeks - Double-Blind Phase | FVC is the volume of air that can be forcibly blown out after full inspiration. | baseline, 16 weeks | 
| Post-treatment Forced Vital Capacity (FVC) at 32 Weeks - Double-Blind Phase | FVC is the volume of air that can be forcibly blown out after full inspiration. | baseline, 32 weeks | 
| Post-treatment Forced Vital Capacity (FVC) at 48 Weeks - Double-Blind Phase | FVC is the volume of air that can be forcibly blown out after full inspiration. | baseline, 48 weeks | 
| Post-treatment Forced Vital Capacity (FVC) at 64 Weeks - Double-Blind Phase | FVC is the volume of air that can be forcibly blown out after full inspiration. | baseline, 64 weeks | 
| Post-treatment Forced Vital Capacity (FVC) at 80 Weeks - Double-Blind Phase | FVC is the volume of air that can be forcibly blown out after full inspiration. | baseline, 80 weeks | 
| Post-treatment Forced Vital Capacity (FVC) at 96 Weeks - Double-Blind Phase | FVC is the volume of air that can be forcibly blown out after full inspiration. | baseline, 96 weeks | 
| Borg Scale of Dyspnea at Isotime After 96 Weeks - Double-Blind Phase | Borg scale assessed degreee of discomfort on a scale from 0 (Nothing at all) to 10 (Maximal) | baseline, 96 weeks | 
| Borg Scale of Peak Dyspnea After 96 Weeks - Double-Blind Phase | Borg scale assessed degreee of discomfort on a scale from 0 (Nothing at all) to 10 (Maximal) | baseline, 96 weeks | 
| Borg Scale of Peak Leg Discomfort After 96 Weeks - Double-Blind Phase | Borg scale assessed degreee of discomfort on a scale from 0 (Nothing at all) to 10 (Maximal) | baseline, 96 weeks | 
| Change From Baseline in Physician Global Evaluation at 8 Weeks - Double-Blind Phase | The evaluation represented the global opinion of the overall clinical condition on a scale of: 1-2 (Poor), 3-4 (Fair), 5-6 (Good), 7-8 (Excellent) | baseline, 8 weeks | 
| Change From Baseline in Physician Global Evaluation at 16 Weeks - Double-Blind Phase | The evaluation represented the global opinion of the overall clinical condition on a scale of: 1-2 (Poor), 3-4 (Fair), 5-6 (Good), 7-8 (Excellent) | baseline, 16 weeks | 
| Change From Baseline in Physician Global Evaluation at 32 Weeks - Double-Blind Phase | The evaluation represented the global opinion of the overall clinical condition on a scale of: 1-2 (Poor), 3-4 (Fair), 5-6 (Good), 7-8 (Excellent) | baseline, 32 weeks | 
| Change From Baseline in Physician Global Evaluation at 48 Weeks - Double-Blind Phase | The evaluation represented the global opinion of the overall clinical condition on a scale of: 1-2 (Poor), 3-4 (Fair), 5-6 (Good), 7-8 (Excellent) | baseline, 48 weeks | 
| Change From Baseline in Physician Global Evaluation at 64 Weeks - Double-Blind Phase | The evaluation represented the global opinion of the overall clinical condition on a scale of: 1-2 (Poor), 3-4 (Fair), 5-6 (Good), 7-8 (Excellent) | baseline, 64 weeks | 
| Change From Baseline in Physician Global Evaluation at 80 Weeks - Double-Blind Phase | The evaluation represented the global opinion of the overall clinical condition on a scale of: 1-2 (Poor), 3-4 (Fair), 5-6 (Good), 7-8 (Excellent) | baseline, 80 weeks | 
| Change From Baseline in Physician Global Evaluation at 96 Weeks - Double-Blind Phase | The evaluation represented the global opinion of the overall clinical condition on a scale of: 1-2 (Poor), 3-4 (Fair), 5-6 (Good), 7-8 (Excellent) | baseline, 96 weeks | 
| Change From Baseline in Patient Global Evaluation at 8 Weeks - Double-Blind Phase | The evaluation represented the global opinion of the overall clinical condition on a scale of: 1-2 (Poor), 3-4 (Fair), 5-6 (Good), 7-8 (Excellent) | baseline, 8 weeks | 
| Change From Baseline in Patient Global Evaluation at 16 Weeks - Double-Blind Phase | The evaluation represented the global opinion of the overall clinical condition on a scale of: 1-2 (Poor), 3-4 (Fair), 5-6 (Good), 7-8 (Excellent) | baseline, 16 weeks | 
| Change From Baseline in Patient Global Evaluation at 32 Weeks - Double-Blind Phase | The evaluation represented the global opinion of the overall clinical condition on a scale of: 1-2 (Poor), 3-4 (Fair), 5-6 (Good), 7-8 (Excellent) | baseline, 32 weeks | 
| Change From Baseline in Patient Global Evaluation at 48 Weeks - Double-Blind Phase | The evaluation represented the global opinion of the overall clinical condition on a scale of: 1-2 (Poor), 3-4 (Fair), 5-6 (Good), 7-8 (Excellent) | baseline, 48 weeks | 
| Change From Baseline in Patient Global Evaluation at 64 Weeks - Double-Blind Phase | The evaluation represented the global opinion of the overall clinical condition on a scale of: 1-2 (Poor), 3-4 (Fair), 5-6 (Good), 7-8 (Excellent) | baseline, 64 weeks | 
| Change From Baseline in Patient Global Evaluation at 80 Weeks - Double-Blind Phase | The evaluation represented the global opinion of the overall clinical condition on a scale of: 1-2 (Poor), 3-4 (Fair), 5-6 (Good), 7-8 (Excellent) | baseline, 80 weeks | 
| Change From Baseline in Patient Global Evaluation at 96 Weeks - Double-Blind Phase | The evaluation represented the global opinion of the overall clinical condition on a scale of: 1-2 (Poor), 3-4 (Fair), 5-6 (Good), 7-8 (Excellent) | baseline, 96 weeks | 
| Saint George's Respiratory Questionnaire Total Score at 96 Weeks - Double-Blind Phase | Score summarises the impact of disease on overall health status with zero indicating best health status and 100 indicating worst possible health status. | baseline, 96 weeks | 
| Saint George's Respiratory Questionnaire Activity Component Score at 96 Weeks - Double-Blind Phase | Score summarises the impact of disease on overall health status with zero indicating best health status and 100 indicating worst possible health status. | baseline, 96 weeks | 
| Saint George's Respiratory Questionnaire Impact Component Score at 96 Weeks - Double-Blind Phase | Score summarises the impact of disease on overall health status with zero indicating best health status and 100 indicating worst possible health status. | baseline, 96 weeks | 
| Saint George's Respiratory Questionnaire Symptoms Component Score at 96 Weeks - Double-Blind Phase | Score summarises the impact of disease on overall health status with zero indicating best health status and 100 indicating worst possible health status. | baseline, 96 weeks | 
| Patients With COPD Exacerbation (Survival Analysis) - Double-Blind Phase | COPD exacerbation is a complex of symptoms related to COPD with a duration of three days or more requiring a change of treatment. | baseline, 96 weeks | 
| 90% Constant Work Rate (CWR) Treadmill Endurance Time at 100 Weeks - Open-Label Phase | Efficacy was assessed by measuring the exercise duration during a treadmill exercise test. | baseline, 100 weeks | 
| Post-treatment Forced Expiratory Volume in 1 Second (FEV1) at 100 Weeks - Open-Label Phase | FEV1 is the maximal amount of air you can forcefully exhale in one second. | baseline, 100 weeks | 
| Post-treatment Forced Vital Capacity (FVC) at 100 Weeks - Open-Label Phase | FVC is the volume of air that can be forcibly blown out after full inspiration. | baseline, 100 weeks | 
| Saint George's Respiratory Questionnaire Total Score at 100 Weeks - Open-Label Phase | Score summarises the impact of disease on overall health status with zero indicating best health status and 100 indicating worst possible health status. | baseline, 100 weeks | 
| Saint George's Respiratory Questionnaire Activity Component Score at 100 Weeks - Open-Label Phase | Score summarises the impact of disease on overall health status with zero indicating best health status and 100 indicating worst possible health status. | baseline, 100 weeks | 
| Saint George's Respiratory Questionnaire Impact Component Score at 100 Weeks - Open-Label Phase | Score summarises the impact of disease on overall health status with zero indicating best health status and 100 indicating worst possible health status. | baseline, 100 weeks | 
| Saint George's Respiratory Questionnaire Symptoms Component Score at 100 Weeks - Open-Label Phase | Score summarises the impact of disease on overall health status with zero indicating best health status and 100 indicating worst possible health status. | baseline, 100 weeks | 
| Clinical Relevant Abnormalities for Vital Signs and Physical Examination, Including Vital Status | Clinical Relevant Abnormalities for Vital Signs and Physical examination, including vital status. Any new or clinically relevant worsening of baseline conditions was reported as Adverse Events. | From first drug administration until 30 days after last drug administration |