Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
This is a randomised, double-blind, double-dummy, multinational, multicentre, parallel group trial comparing tiotropium (18 mcg) inhalation capsule via HandiHaler and salmeterol (50 mcg) via MDI in patients with COPD. There will be a two-week run-in period followed by a 52-week randomised treatment phase. Patients who withdraw prematurely from trial medication will be encouraged to remain in the trial and participate in follow-up telephone contacts until their predicted normal exit date from the trial (i.e. 52 weeks after taking the first dose of randomised treatment). The phone calls will be made at all scheduled visits. The primary objective of this study is to compare the effect of tiotropium (18 mcg) inhalation capsule via HandiHaler with that of salmeterol (50 mcg) via MDI on COPD exacerbations. The primary endpoint is time to first COPD exacerbation during the 52 week randomised treatment period. A COPD exacerbation will be defined as a complex of respiratory events / symptoms (increase or new onset) of more than one of the following: cough, sputum, wheezing, dyspnoea or chest tightness with at least one symptom lasting at least three days requiring treatment with antibiotics and/or systemic steroids and/or hospitalisation. The onset of an exacerbation is defined as the onset of the first new or increased reported symptom. The end of the exacerbation should be recorded as defined by the investigator. Only COPD exacerbations with onset during randomised treatment will be included in the analysis.
Interventions
DRUGTiotropium bromide
18 mcg/daily
DRUGSalmeterol
100 mcg/daily
DRUGPlacebo Salmeterol
Placebo identical to Salmeterol device
Placebo identical to Tiotropium device
Sponsors
Pfizer
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. All patients must have a diagnosis of chronic obstructive pulmonary disease (COPD) and must meet the following criteria at Visit 1: Patients must have relatively stable, moderate to very severe airway obstruction with a post-bronchodilator FEV1 \<=70% of predicted normal and FEV1 \<=70% of FVC post-bronchodilator (i.e. 30 minutes after inhalation of 4 puffs of 100 µg salbutamol or equivalent SABA). Predicted normal values will be calculated according to ECSC. For Height measured in inches Males: FEV1 predicted (L) = 4.30 x (height (inches) / 39.37)-0.029 x age (yrs) - 2.49 Females:FEV1 predicted (L) = 3.95 x (height (inches) / 39.37)-0.025 x age (yrs) - 2.60 For Height measured in metres Males: FEV1 predicted (L) = 4.30 x (height (metres)) - 0.029 x age (years) - 2.49 Females: FEV1 predicted (L) = 3.95 x (height (metres)) - 0.025 x age (years) - 2.60 2. All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial. 3. Male or female patients 40 years of age or older. 4. Patients with a history of at least one exacerbation within the past year requiring treatment with either antibiotics and/or systemic steroids and/or hospitalisation. 5. Patients must be current or ex-smokers with a smoking history of \>= 10 pack-years. (Patients who have never smoked cigarettes must be excluded.) 6. Patients must be able to perform all study-related procedures including technically acceptable pulmonary function tests (PFTs). 7. Patients must be able to inhale medication in a competent manner from the HandiHaler and a metered dose inhaler (MDI). 8. Patients must be able to maintain records (patient daily diary card) during the study period as required in the protocol.
Exclusion criteria
1. Significant diseases other than COPD. A significant disease is defined as a disease or condition which, in the opinion of the investigator, may put the patient at risk because of participation in the study or may influence either the results of the study or the patients' ability to participate in the study. 2. Patients with a diagnosis of asthma. 3. Patients with a life-threatening pulmonary obstruction, or a history of cystic fibrosis. 4. Patients with known active tuberculosis. 5. Patients with a known symptomatic prostatic hyperplasia or bladder neck obstruction. Patients with symptomatically-controlled prostatic hyperplasia on medication may be included and should continue their medication. 6. Patients with known narrow-angle glaucoma. 7. Patients with a history of myocardial infarction within the year prior to Visit 1. 8. Patients with a history of hospital admission for heart failure within the year prior to Visit 1. 9. Patients with cardiac arrhythmia requiring medical or surgical treatment. 10. Patients with severe cardiovascular disorders. 11. Patients with a known hypersensitivity to anticholinergic drugs, beta-adrenergics, lactose or any other component of the medication delivery system. 12. Patients with known moderate or severe renal insufficiency (known creatinine clearance of \<= 50 mL/min). 13. Patients with untreated known hypokalaemia. 14. Patients with untreated known thyrotoxicosis. 15. Patients with brittle/unstable diabetes mellitus. 16. Patients with a history of and/or active significant alcohol or drug abuse. See exclusion criterion 1. 17. Patients who have taken an investigational drug within 30 days or six half-lives (whichever is greater) prior to Screening Visit (Visit 1). 18. Use of systemic corticosteroid medication at unstable doses (i.e less than six weeks on stable dose) or at doses in excess of the equivalent of 10 mg prednisolone per day or 20 mg every other day. 19. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e oral contraceptives, intrauterine devices, diaphragm or subdermal implants e.g Norplant) for at least three months prior to, and for the duration of the trial. 20. Previous participation (receipt of randomised treatment) in this study. 21. Patients who are currently participating in another study. 22. Patients with any respiratory infection or COPD exacerbation in the four weeks prior to the Screening Visit (Visit 1) or during the run-in period should be postponed. In the case of a respiratory infection or COPD exacerbation during the run-in period, the latter may be extended up to four weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| First Occurrence of (Moderate or Severe) COPD Exacerbation | 52 weeks | First occurrence analysed by Cox regression as time to first exacerbation and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One COPD Exacerbation | 52 weeks | An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| COPD Exacerbations Per Patient-year | 52 weeks | — |
| First Occurrence of COPD Exacerbation Leading to Hospitalization | 52 weeks | First occurrence analysed by Cox regression as time to first exacerbation leading to hospitalisation and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| Number of Participants With at Least One COPD Exacerbation Leading to Hospitalisation | 52 weeks | An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| Occurrence of Premature Discontinuation of Trial Medication | 52 weeks | Occurrence analysed by Cox regression as time to premature discontinuation of trial medication and reported as hazard ratio |
| Number of Participants With Premature Discontinuation of Trial Medication | 52 weeks | — |
| First Occurrence of COPD Exacerbation or Discontinuation of Trial Medication Because of Worsening of Underlying Disease, Whichever Comes First | 52 weeks | First occurrence analysed by Cox regression as time to first exacerbation or discontinuation of trial medication because of worsening of underlying disease, whichever comes first and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| First Occurrence of COPD Exacerbations Treated With Systemic Steroids | 52 weeks | First occurrence analysed by Cox regression as time to first exacerbation treated with systemic steroids and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| First Occurrence of COPD Exacerbations Treated With Antibiotics | 52 weeks | First occurrence analysed by Cox regression as time to first exacerbation treated with antibiotics and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| First Occurrence of COPD Exacerbations Treated With Systemic Steroids and Antibiotics | 52 weeks | First occurrence analysed by Cox regression as time to first exacerbation treated with systemic steroids and antibiotics and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| COPD Exacerbations Treated With Systemic Steroids Per Patient-year | 52 weeks | An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| COPD Exacerbations Treated With Antibiotics Per Patient-year | 52 weeks | An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| COPD Exacerbations Treated With Systemic Steroids and Antibiotics Per Patient-year | 52 weeks | An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 1 | 16 weeks | PEFR means peak expiratory flow rate and is measured in liter per minute |
| COPD Exacerbations Per Patient-year Leading to Hospitalisation | 52 weeks | An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation). |
| Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 3 | 16 weeks | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 4 | 16 weeks | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 5 | 16 weeks | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 6 | 16 weeks | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 7 | 16 weeks | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 8 | 16 weeks | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 9 | 16 weeks | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 10 | 16 weeks | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 11 | 16 weeks | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 12 | 16 weeks | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 13 | 16 weeks | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 14 | 16 weeks | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 15 | 16 weeks | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 16 | 16 weeks | PEFR means peak expiratory flow rate and is measured in liter per minute |
| Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 2 | 16 weeks | PEFR means peak expiratory flow rate and is measured in liter per minute |
Countries
Austria, Belgium, Bulgaria, Czechia, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Latvia, Lithuania, Netherlands, Norway, Poland, Portugal, Romania, Russia, Slovakia, Slovenia, Spain, Turkey (Türkiye), Ukraine, United Kingdom
Participant flow
Pre-assignment details
There were 8 patients (4:4 on Tiotropium and Salmeterol respectively) randomized but not treated
Participants by arm
| Arm | Count |
|---|---|
| Tiotropium Tiotropium 18 mcg once daily (QD) inhalation (powder) via HandiHaler® and matching Placebo metered dose inhaler (MDI) twice daily (BID) | 3,707 |
| Salmeterol Salmeterol 50 mcg (2 actuations of 25 mcg) twice daily inhalation (suspension) via MDI and Placebo HandiHaler® once daily | 3,669 |
| Total | 7,376 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 264 | 292 |
| Overall Study | Individual different reasons | 24 | 34 |
| Overall Study | Lack of Efficacy | 32 | 24 |
| Overall Study | Lost to Follow-up | 7 | 15 |
| Overall Study | Protocol Violation | 66 | 74 |
| Overall Study | Withdrawal by Subject | 192 | 209 |
Baseline characteristics
| Characteristic | Tiotropium | Salmeterol | Total |
|---|---|---|---|
| Age, Continuous | 62.9 Years STANDARD_DEVIATION 9 | 62.8 Years STANDARD_DEVIATION 9 | 62.9 Years STANDARD_DEVIATION 9 |
| Race/Ethnicity, Customized Asian | 5 Participants | 3 Participants | 8 Participants |
| Race/Ethnicity, Customized Black | 9 Participants | 9 Participants | 18 Participants |
| Race/Ethnicity, Customized White | 3693 Participants | 3657 Participants | 7350 Participants |
| Sex: Female, Male Female | 948 Participants | 922 Participants | 1870 Participants |
| Sex: Female, Male Male | 2759 Participants | 2747 Participants | 5506 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 495 / 3,707 | 581 / 3,669 |
| serious Total, serious adverse events | 545 / 3,707 | 606 / 3,669 |
Outcome results
Primary
First Occurrence of (Moderate or Severe) COPD Exacerbation
First occurrence analysed by Cox regression as time to first exacerbation and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
Time frame: 52 weeks
Population: All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tiotropium | First Occurrence of (Moderate or Severe) COPD Exacerbation | 1277 number of first occurrences |
| Salmeterol | First Occurrence of (Moderate or Severe) COPD Exacerbation | 1414 number of first occurrences |
Comparison: Tiotropium versus Salmeterolp-value: <0.000195% CI: [0.77, 0.9]Regression, Cox
Secondary
COPD Exacerbations Per Patient-year
Time frame: 52 weeks
Population: All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tiotropium | COPD Exacerbations Per Patient-year | 0.64 exacerbations per patient-year |
| Salmeterol | COPD Exacerbations Per Patient-year | 0.72 exacerbations per patient-year |
Comparison: Tiotropium versus Salmeterolp-value: 0.001795% CI: [0.83, 0.96]Poisson regression
Secondary
COPD Exacerbations Per Patient-year Leading to Hospitalisation
An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
Time frame: 52 weeks
Population: All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tiotropium | COPD Exacerbations Per Patient-year Leading to Hospitalisation | 0.09 Hospitalizations per patient-year |
| Salmeterol | COPD Exacerbations Per Patient-year Leading to Hospitalisation | 0.13 Hospitalizations per patient-year |
Comparison: Tiotropium vs. Salmeterolp-value: <0.000195% CI: [0.66, 0.82]Poisson regression
Secondary
COPD Exacerbations Treated With Antibiotics Per Patient-year
An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
Time frame: 52 weeks
Population: All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tiotropium | COPD Exacerbations Treated With Antibiotics Per Patient-year | 0.53 exacerbations per patient-year |
| Salmeterol | COPD Exacerbations Treated With Antibiotics Per Patient-year | 0.59 exacerbations per patient-year |
Comparison: Tiotropium versus Salmeterolp-value: 0.003695% CI: [0.84, 0.97]Poisson regression
Secondary
COPD Exacerbations Treated With Systemic Steroids and Antibiotics Per Patient-year
An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
Time frame: 52 weeks
Population: All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tiotropium | COPD Exacerbations Treated With Systemic Steroids and Antibiotics Per Patient-year | 0.23 exacerbations per patient-year |
| Salmeterol | COPD Exacerbations Treated With Systemic Steroids and Antibiotics Per Patient-year | 0.28 exacerbations per patient-year |
Comparison: Tiotropium versus Salmeterolp-value: <0.000195% CI: [0.73, 0.88]Poisson regression
Secondary
COPD Exacerbations Treated With Systemic Steroids Per Patient-year
An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
Time frame: 52 weeks
Population: All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tiotropium | COPD Exacerbations Treated With Systemic Steroids Per Patient-year | 0.33 exacerbations per patient-year |
| Salmeterol | COPD Exacerbations Treated With Systemic Steroids Per Patient-year | 0.41 exacerbations per patient-year |
Comparison: Tiotropium versus Salmeterolp-value: <0.000195% CI: [0.76, 0.9]Poisson regression
Secondary
First Occurrence of COPD Exacerbation Leading to Hospitalization
First occurrence analysed by Cox regression as time to first exacerbation leading to hospitalisation and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
Time frame: 52 weeks
Population: All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tiotropium | First Occurrence of COPD Exacerbation Leading to Hospitalization | 262 number of first occurrences |
| Salmeterol | First Occurrence of COPD Exacerbation Leading to Hospitalization | 336 number of first occurrences |
Comparison: Tiotropium versus Salmeterolp-value: <0.000195% CI: [0.61, 0.85]Regression, Cox
Secondary
First Occurrence of COPD Exacerbation or Discontinuation of Trial Medication Because of Worsening of Underlying Disease, Whichever Comes First
First occurrence analysed by Cox regression as time to first exacerbation or discontinuation of trial medication because of worsening of underlying disease, whichever comes first and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
Time frame: 52 weeks
Population: All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tiotropium | First Occurrence of COPD Exacerbation or Discontinuation of Trial Medication Because of Worsening of Underlying Disease, Whichever Comes First | 1316 number of first occurrences |
| Salmeterol | First Occurrence of COPD Exacerbation or Discontinuation of Trial Medication Because of Worsening of Underlying Disease, Whichever Comes First | 1448 number of first occurrences |
Comparison: Tiotropium versus Salmeterolp-value: <0.000195% CI: [0.78, 0.91]Regression, Cox
Secondary
First Occurrence of COPD Exacerbations Treated With Antibiotics
First occurrence analysed by Cox regression as time to first exacerbation treated with antibiotics and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
Time frame: 52 weeks
Population: All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tiotropium | First Occurrence of COPD Exacerbations Treated With Antibiotics | 1154 number of first occurrences |
| Salmeterol | First Occurrence of COPD Exacerbations Treated With Antibiotics | 1259 number of first occurrences |
Comparison: Tiotropium versus Salmeterolp-value: <0.000195% CI: [0.78, 0.92]Regression, Cox
Secondary
First Occurrence of COPD Exacerbations Treated With Systemic Steroids
First occurrence analysed by Cox regression as time to first exacerbation treated with systemic steroids and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
Time frame: 52 weeks
Population: All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tiotropium | First Occurrence of COPD Exacerbations Treated With Systemic Steroids | 715 number of first occurrences |
| Salmeterol | First Occurrence of COPD Exacerbations Treated With Systemic Steroids | 852 number of first occurrences |
Comparison: Tiotropium versus Salmeterolp-value: <0.000195% CI: [0.69, 0.85]Regression, Cox
Secondary
First Occurrence of COPD Exacerbations Treated With Systemic Steroids and Antibiotics
First occurrence analysed by Cox regression as time to first exacerbation treated with systemic steroids and antibiotics and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
Time frame: 52 weeks
Population: All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tiotropium | First Occurrence of COPD Exacerbations Treated With Systemic Steroids and Antibiotics | 562 number of first occurrences |
| Salmeterol | First Occurrence of COPD Exacerbations Treated With Systemic Steroids and Antibiotics | 671 number of first occurrences |
Comparison: Tiotropium versus Salmeterolp-value: <0.000195% CI: [0.68, 0.86]Regression, Cox
Secondary
Number of Participants With at Least One COPD Exacerbation
An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
Time frame: 52 weeks
Population: All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tiotropium | Number of Participants With at Least One COPD Exacerbation | Participants with (at least one) event | 1277 Participants |
| Tiotropium | Number of Participants With at Least One COPD Exacerbation | Participants with no event | 2430 Participants |
| Salmeterol | Number of Participants With at Least One COPD Exacerbation | Participants with (at least one) event | 1414 Participants |
| Salmeterol | Number of Participants With at Least One COPD Exacerbation | Participants with no event | 2255 Participants |
Comparison: Tiotropium versus Salmeterolp-value: 0.000295% CI: [0.85, 0.95]Cochran-Mantel-Haenszel
Secondary
Number of Participants With at Least One COPD Exacerbation Leading to Hospitalisation
An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).
Time frame: 52 weeks
Population: All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tiotropium | Number of Participants With at Least One COPD Exacerbation Leading to Hospitalisation | Participants with (at least one) event | 262 Participants |
| Tiotropium | Number of Participants With at Least One COPD Exacerbation Leading to Hospitalisation | Participants with no event | 3445 Participants |
| Salmeterol | Number of Participants With at Least One COPD Exacerbation Leading to Hospitalisation | Participants with (at least one) event | 336 Participants |
| Salmeterol | Number of Participants With at Least One COPD Exacerbation Leading to Hospitalisation | Participants with no event | 3333 Participants |
Comparison: Tiotropium versus Salmeterolp-value: 0.000595% CI: [0.66, 0.89]Cochran-Mantel-Haenszel
Secondary
Number of Participants With Premature Discontinuation of Trial Medication
Time frame: 52 weeks
Population: All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tiotropium | Number of Participants With Premature Discontinuation of Trial Medication | Participants with (at least one) event | 585 Participants |
| Tiotropium | Number of Participants With Premature Discontinuation of Trial Medication | Participants with no event | 3122 Participants |
| Salmeterol | Number of Participants With Premature Discontinuation of Trial Medication | Participants with (at least one) event | 648 Participants |
| Salmeterol | Number of Participants With Premature Discontinuation of Trial Medication | Participants with no event | 3021 Participants |
Comparison: Tiotropium versus Salmeterolp-value: 0.040695% CI: [0.82, 1]Cochran-Mantel-Haenszel
Secondary
Occurrence of Premature Discontinuation of Trial Medication
Occurrence analysed by Cox regression as time to premature discontinuation of trial medication and reported as hazard ratio
Time frame: 52 weeks
Population: All patients who received study medication, were randomised, and were documented to have taken at least one dose of double-blind treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tiotropium | Occurrence of Premature Discontinuation of Trial Medication | 585 number of first occurrences |
| Salmeterol | Occurrence of Premature Discontinuation of Trial Medication | 648 number of first occurrences |
Comparison: Tiotropium versus Salmeterolp-value: 0.024295% CI: [0.78, 0.98]Regression, Cox
Secondary
Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 1
PEFR means peak expiratory flow rate and is measured in liter per minute
Time frame: 16 weeks
Population: All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 1 | 222.85 liter per minute (L/min) | Standard Error 0.81 |
| Salmeterol | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 1 | 224.45 liter per minute (L/min) | Standard Error 0.81 |
Comparison: Tiotropium versus Salmeterolp-value: 0.103595% CI: [-3.53, 0.33]Mixed Effects Repeated Measures Model
Secondary
Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 10
PEFR means peak expiratory flow rate and is measured in liter per minute
Time frame: 16 weeks
Population: All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 10 | 230.30 liter per minute (L/min) | Standard Error 0.82 |
| Salmeterol | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 10 | 231.27 liter per minute (L/min) | Standard Error 0.82 |
Comparison: Tiotropium versus Salmeterolp-value: 0.329795% CI: [-2.92, 0.98]Mixed Effects Repeated Measures Model
Secondary
Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 11
PEFR means peak expiratory flow rate and is measured in liter per minute
Time frame: 16 weeks
Population: All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 11 | 230.61 liter per minute (L/min) | Standard Error 0.82 |
| Salmeterol | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 11 | 231.91 liter per minute (L/min) | Standard Error 0.82 |
Comparison: Tiotropium versus Salmeterolp-value: 0.190495% CI: [-3.25, 0.65]Mixed Effects Repeated Measures Model
Secondary
Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 12
PEFR means peak expiratory flow rate and is measured in liter per minute
Time frame: 16 weeks
Population: All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 12 | 231.04 liter per minute (L/min) | Standard Error 0.82 |
| Salmeterol | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 12 | 232.04 liter per minute (L/min) | Standard Error 0.82 |
Comparison: Tiotropium versus Salmeterolp-value: 0.317295% CI: [-2.94, 0.95]Mixed Effects Repeated Measures Model
Secondary
Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 13
PEFR means peak expiratory flow rate and is measured in liter per minute
Time frame: 16 weeks
Population: All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 13 | 231.23 liter per minute (L/min) | Standard Error 0.82 |
| Salmeterol | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 13 | 231.89 liter per minute (L/min) | Standard Error 0.82 |
Comparison: Tiotropium versus Salmeterolp-value: 0.501795% CI: [-2.62, 1.28]Mixed Effects Repeated Measures Model
Secondary
Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 14
PEFR means peak expiratory flow rate and is measured in liter per minute
Time frame: 16 weeks
Population: All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 14 | 231.19 liter per minute (L/min) | Standard Error 0.82 |
| Salmeterol | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 14 | 232.42 liter per minute (L/min) | Standard Error 0.82 |
Comparison: Tiotropium versus Salmeterolp-value: 0.217495% CI: [-3.18, 0.72]Mixed Effects Repeated Measures Model
Secondary
Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 15
PEFR means peak expiratory flow rate and is measured in liter per minute
Time frame: 16 weeks
Population: All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 15 | 231.64 liter per minute (L/min) | Standard Error 0.82 |
| Salmeterol | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 15 | 232.75 liter per minute (L/min) | Standard Error 0.82 |
Comparison: Tiotropium versus Salmeterolp-value: 0.268295% CI: [-3.05, 0.85]Mixed Effects Repeated Measures Model
Secondary
Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 16
PEFR means peak expiratory flow rate and is measured in liter per minute
Time frame: 16 weeks
Population: All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 16 | 232.06 liter per minute (L/min) | Standard Error 0.82 |
| Salmeterol | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 16 | 232.65 liter per minute (L/min) | Standard Error 0.82 |
Comparison: Tiotropium versus Salmeterolp-value: 0.55295% CI: [-2.55, 1.36]Mixed Effects Repeated Measures Model
Secondary
Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 2
PEFR means peak expiratory flow rate and is measured in liter per minute
Time frame: 16 weeks
Population: All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 2 | 225.15 liter per minute (L/min) | Standard Error 0.81 |
| Salmeterol | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 2 | 227.21 liter per minute (L/min) | Standard Error 0.81 |
Comparison: Tiotropium versus Salmeterolp-value: 0.036995% CI: [-3.99, -0.12]Mixed Effects Repeated Measures Model
Secondary
Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 3
PEFR means peak expiratory flow rate and is measured in liter per minute
Time frame: 16 weeks
Population: All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 3 | 226.31 liter per minute (L/min) | Standard Error 0.81 |
| Salmeterol | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 3 | 228.38 liter per minute (L/min) | Standard Error 0.81 |
Comparison: Tiotropium versus Salmeterolp-value: 0.036295% CI: [-4, -0.13]Mixed Effects Repeated Measures Model
Secondary
Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 4
PEFR means peak expiratory flow rate and is measured in liter per minute
Time frame: 16 weeks
Population: All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 4 | 227.37 liter per minute (L/min) | Standard Error 0.81 |
| Salmeterol | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 4 | 229.25 liter per minute (L/min) | Standard Error 0.81 |
Comparison: Tiotropium versus Salmeterolp-value: 0.057395% CI: [-3.82, 0.06]Mixed Effects Repeated Measures Model
Secondary
Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 5
PEFR means peak expiratory flow rate and is measured in liter per minute
Time frame: 16 weeks
Population: All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 5 | 228.27 liter per minute (L/min) | Standard Error 0.81 |
| Salmeterol | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 5 | 229.37 liter per minute (L/min) | Standard Error 0.81 |
Comparison: Tiotropium versus Salmeterolp-value: 0.264195% CI: [-3.04, 0.83]Mixed Effects Repeated Measures Model
Secondary
Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 6
PEFR means peak expiratory flow rate and is measured in liter per minute
Time frame: 16 weeks
Population: All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 6 | 228.80 liter per minute (L/min) | Standard Error 0.82 |
| Salmeterol | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 6 | 229.81 liter per minute (L/min) | Standard Error 0.81 |
Comparison: Tiotropium versus Salmeterolp-value: 0.306895% CI: [-2.95, 0.93]Mixed Effects Repeated Measures Model
Secondary
Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 7
PEFR means peak expiratory flow rate and is measured in liter per minute
Time frame: 16 weeks
Population: All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 7 | 229.35 liter per minute (L/min) | Standard Error 0.82 |
| Salmeterol | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 7 | 230.13 liter per minute (L/min) | Standard Error 0.82 |
Comparison: Tiotropium versus Salmeterolp-value: 0.429995% CI: [-2.72, 1.16]Mixed Effects Repeated Measures Model
Secondary
Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 8
PEFR means peak expiratory flow rate and is measured in liter per minute
Time frame: 16 weeks
Population: All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 8 | 229.95 liter per minute (L/min) | Standard Error 0.82 |
| Salmeterol | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 8 | 230.43 liter per minute (L/min) | Standard Error 0.82 |
Comparison: Tiotropium versus Salmeterolp-value: 0.627795% CI: [-2.42, 1.46]Mixed Effects Repeated Measures Model
Secondary
Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 9
PEFR means peak expiratory flow rate and is measured in liter per minute
Time frame: 16 weeks
Population: All patients who received study medication, were randomised, were documented to have taken at least one dose of double-blind treatment, gave informed consent to genotyping, took part in the pre-specified part of the genotyping analysis, and who have evaluable blood samples
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 9 | 229.72 liter per minute (L/min) | Standard Error 0.82 |
| Salmeterol | Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 9 | 230.57 liter per minute (L/min) | Standard Error 0.82 |
Comparison: Tiotropium versus Salmeterolp-value: 0.393195% CI: [-2.8, 1.1]Mixed Effects Repeated Measures Model