Tiotropium / Respimat One Year Study in COPD.

Study Overview
=================
Brief Summary
-----------------
The objective of the study is to evaluate the long-term (one year) efficacy and safety of tiotropium delivered by the Respimat inhaler in patients with COPD. Specifically, the study will examine the effect of treatment on COPD exacerbations.

Official Title
-----------------
Efficacy {FEV1, COPD Exacerbations & HRQoL} & Safety of 5mcg Tiotropium Respimat in COPD

Conditions
-----------------
Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
-----------------
* Device: Respimat
* Drug: Tiotropium


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female At least 40 years old Smoker or ex-smoker Smoking history > 10 pack-years Forced Expiratory Volume in 1 Second (FEV1) < 60% predicted Exclusion Criteria: Recent history of myocardial infarction, life-threatening cardiac arrhythmia or hospitalisation for cardiac failure History of asthma or allergic conditions. Malignancy requiring treatment within past 5 years Life-threatening pulmonary obstruction, cystic fibrosis or clinically evident bronchiectasis Known active tuberculosis Known hypersensitivity to anticholinergic drugs.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Parallel Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Tiotropium<br>Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded) | Drug: Tiotropium<br> <br> |
| Other: Placebo<br>Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded) | Device: Respimat<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 337 | Trough FEV1 is defined as the FEV1 measured at the -10 min time point at the end of the dosing interval (24 h post drug administration). | Baseline and Day 337 | 
| Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Time to first COPD exacerbation (defined as a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment). Time is days from start of study treatment to onset of exacerbation. | During actual study treatment period (planned Day 1 to Day 337) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29 | Trough FEV1 is the mean volume of air that can be forced out in one second after taking a deep breath approximately 24 hours after the last administration of study drug. | Baseline and Day 29 | 
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 169 | Trough FEV1 is the mean volume of air that can be forced out in one second after taking a deep breath approximately 24 hours after the last administration of study drug. | Baseline and Day 169 | 
| Number of COPD Exacerbations Per Patient - Exposure Adjusted | Number of COPD exacerbations (defined as a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment) per patient adjusted by length of treatment exposure (i.e. number of exacerbations multiplied by 365.25 and then divided by days of treatment exposure) | During actual study treatment period (planned Day 1 to Day 337) | 
| Number of COPD Exacerbations Per Patient - naïve Estimate | Number of COPD exacerbations (defined as a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment) per patient not adjusted for treatment exposure (i.e. naïve estimate) | During actual study treatment period (planned Day 1 to Day 337) | 
| Number of Patients With at Least One COPD Exacerbation | Number of patients with at least one COPD exacerbation (defined as a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment) | During actual study treatment period (planned Day 1 to Day 337) | 
| Time to First Hospitalisation for COPD Exacerbation | Time to first hospitalisation for COPD exacerbation (a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment). Time is days from start of study treatment to onset of exacerbation | During actual study treatment period (planned Day 1 to Day 337) | 
| Number of Hospitalisations for COPD Exacerbations Per Patient - Exposure Adjusted | Number of hospitalisations for COPD exacerbations (a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment) per patient adjusted by length of treatment exposure (i.e. no. of exacerbations multiplied by 365.25 and then divided by days of treatment exposure) | During actual study treatment period (planned Day 1 to Day 337) | 
| Number of Hospitalisations for COPD Exacerbations Per Patient - naïve Estimate | Number of hospitalisations for COPD exacerbations (a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment) per patient not adjusted for treatment exposure (i.e. naïve estimate) | During actual study treatment period (planned Day 1 to Day 337) | 
| Number of Patients With at Least One Hospitalisation for a COPD Exacerbation | Number of patients with at least one hospitalisation for a COPD exacerbation (a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment) | During actual study treatment period (planned Day 1 to Day 337) | 
| Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Day 337 | The SGRQ total score measures quality of life on a continuous scale ranging from 0=best state to 100=worst state | Baseline and Day 337 | 
| Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Day 169 | The SGRQ total score measures quality of life on a continuous scale ranging from 0=best state to 100=worst state | Baseline and Day 169 | 
| Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 337 | The SGRQ domain score (symptom, activity and impact) measures quality of life on a continuous scale ranging from 0=best state to 100=worst state | Baseline and Day 337 | 
| Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 169 | The SGRQ domain score (symptom, activity and impact) measures quality of life on a continuous scale ranging from 0=best state to 100=worst state | Baseline and Day 169 | 
| Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 29 | Trough FVC is the mean maximum volume of air that can be forcibly expired from the lungs; measured approximately 24 hours after the last administration of study drug. | Baseline and Day 29 | 
| Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 169 | Trough FVC is the mean maximum volume of air that can be forcibly expired from the lungs; measured approximately 24 hours after the last administration of study drug. | Baseline and Day 169 | 
| Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 337 | Trough FVC is the mean maximum volume of air that can be forcibly expired from the lungs; measured approximately 24 hours after the last administration of study drug. | Baseline and Day 337 | 
| Marked Changes From Baseline in Vital Signs at End of Treatment | Marked changes from baseline in vital signs (diastolic and systolic blood pressure (DBP and SBP) and pulse rate (PR)) at end of treatment. SBP - Increase means SBP >150 mmHg and an increase above baseline of >25 mmHg. SBP - Decrease means SBP <100 mmHg and a decrease below baseline of >10 mmHg. DBP - Increase means DBP >90 mmHg and an increase above baseline of >10 mmHg. DBP - Decrease means DBP <60 mmHg and a decrease below baseline of >10 mmHg. PR - Increase means PR >100 bpm and an increase above baseline of >10 bpm. PR - Decrease means PR <60 bpm and a decrease below baseline of >10 bpm. | Baseline and end of treatment | 
| Clinically Relevant Findings in Physical Examination and ECG | Clinically relevant findings in Physical Examination and ECG at end of treatment | End of treatment |