Pulmonary Disease, Chronic Obstructive
Conditions
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.
Interventions
DEVICERespimat
DRUGTiotropium
Sponsors
Boehringer Ingelheim
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female 2. At least 40 years old 3. Smoker or ex-smoker 4. Smoking history \> 10 pack-years 5. Forced Expiratory Volume in 1 Second (FEV1) \< 60% predicted
Exclusion criteria
1. Recent history of myocardial infarction, life-threatening cardiac arrhythmia or hospitalisation for cardiac failure 2. History of asthma or allergic conditions. 3. Malignancy requiring treatment within past 5 years 4. Life-threatening pulmonary obstruction, cystic fibrosis or clinically evident bronchiectasis 5. Known active tuberculosis 6. Known hypersensitivity to anticholinergic drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 337 | Baseline and 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). |
| Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | During actual study treatment period (planned Day 1 to Day 337) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of COPD Exacerbations Per Patient - Exposure Adjusted | During actual study treatment period (planned Day 1 to Day 337) | 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) |
| Number of COPD Exacerbations Per Patient - naïve Estimate | During actual study treatment period (planned Day 1 to Day 337) | 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) |
| Number of Patients With at Least One COPD Exacerbation | During actual study treatment period (planned Day 1 to Day 337) | 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) |
| Time to First Hospitalisation for COPD Exacerbation | During actual study treatment period (planned Day 1 to Day 337) | 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 |
| Number of Hospitalisations for COPD Exacerbations Per Patient - Exposure Adjusted | During actual study treatment period (planned Day 1 to Day 337) | 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) |
| Number of Hospitalisations for COPD Exacerbations Per Patient - naïve Estimate | During actual study treatment period (planned Day 1 to Day 337) | 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) |
| Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 169 | Baseline and 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 |
| Number of Patients With at Least One Hospitalisation for a COPD Exacerbation | During actual study treatment period (planned Day 1 to Day 337) | 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) |
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29 | Baseline and 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. |
| Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Day 169 | Baseline and Day 169 | The SGRQ total score measures quality of life on a continuous scale ranging from 0=best state to 100=worst state |
| Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 337 | Baseline and 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 |
| Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 29 | Baseline and 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. |
| Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 169 | Baseline and 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. |
| Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 337 | Baseline and 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. |
| Marked Changes From Baseline in Vital Signs at End of Treatment | Baseline and 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. |
| Clinically Relevant Findings in Physical Examination and ECG | End of treatment | Clinically relevant findings in Physical Examination and ECG at end of treatment |
| Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Day 337 | Baseline and Day 337 | The SGRQ total score measures quality of life on a continuous scale ranging from 0=best state to 100=worst state |
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 169 | Baseline and 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. |
Countries
Australia, Brazil, Canada, China, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, India, Ireland, Italy, Lithuania, Malaysia, Mexico, Netherlands, Norway, Portugal, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tiotropium Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded) | 1,952 |
| Placebo Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded) | 1,965 |
| Total | 3,917 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 143 | 156 |
| Overall Study | Lack of Efficacy | 28 | 67 |
| Overall Study | Lost to Follow-up | 22 | 28 |
| Overall Study | Other | 58 | 52 |
| Overall Study | Protocol Violation | 47 | 35 |
| Overall Study | Withdrawal by Subject | 20 | 35 |
Baseline characteristics
| Characteristic | Tiotropium | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 64.8 Years STANDARD_DEVIATION 9.1 | 64.8 Years STANDARD_DEVIATION 9 | 64.80 Years STANDARD_DEVIATION 9 |
| Sex: Female, Male Female | 428 Participants | 452 Participants | 880 Participants |
| Sex: Female, Male Male | 1524 Participants | 1513 Participants | 3037 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 866 / 1,952 | 926 / 1,965 |
| serious Total, serious adverse events | 342 / 1,952 | 336 / 1,965 |
Outcome results
Primary
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).
Time frame: Baseline and Day 337
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. 133 participants from the FAS were excluded due to insufficient FEV1 data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 337 | 0.119 Litres | Standard Error 0.007 |
| Placebo | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 337 | 0.018 Litres | Standard Error 0.007 |
p-value: <0.000195% CI: [0.085, 0.118]ANCOVA
Primary
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.
Time frame: During actual study treatment period (planned Day 1 to Day 337)
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tiotropium | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | NA Days |
| Placebo | Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | NA Days |
Secondary
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
Time frame: Baseline and Day 169
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. Up to 534 participants from the FAS were excluded due to insufficient SGRQ data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Tiotropium | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 169 | Symptoms (N=1704,1688) | -6.555 Units on a scale | Standard Error 0.53 |
| Tiotropium | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 169 | Activities (N=1690,1668) | -3.573 Units on a scale | Standard Error 0.432 |
| Tiotropium | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 169 | Impacts (N=1690,1668) | -4.917 Units on a scale | Standard Error 0.39 |
| Placebo | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 169 | Symptoms (N=1704,1688) | -3.268 Units on a scale | Standard Error 0.532 |
| Placebo | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 169 | Activities (N=1690,1668) | -1.218 Units on a scale | Standard Error 0.435 |
| Placebo | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 169 | Impacts (N=1690,1668) | -2.935 Units on a scale | Standard Error 0.392 |
Secondary
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
Time frame: Baseline and Day 337
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. Up to 534 participants from the FAS were excluded due to insufficient SGRQ data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Tiotropium | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 337 | Symptoms (N=1704,1688) | -7.260 Units on a scale | Standard Error 0.546 |
| Tiotropium | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 337 | Activities (N=1690,1668) | -3.196 Units on a scale | Standard Error 0.456 |
| Tiotropium | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 337 | Impacts (N=1690,1668) | -4.873 Units on a scale | Standard Error 0.409 |
| Placebo | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 337 | Symptoms (N=1704,1688) | -3.307 Units on a scale | Standard Error 0.548 |
| Placebo | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 337 | Activities (N=1690,1668) | -0.226 Units on a scale | Standard Error 0.46 |
| Placebo | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 337 | Impacts (N=1690,1668) | -2.038 Units on a scale | Standard Error 0.412 |
Secondary
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
Time frame: Baseline and Day 169
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. 534 participants from the FAS were excluded due to insufficient SGRQ data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Day 169 | -4.764 Units on a scale | Standard Error 0.348 |
| Placebo | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Day 169 | -2.568 Units on a scale | Standard Error 0.35 |
Secondary
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
Time frame: Baseline and Day 337
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. 534 participants from the FAS were excluded due to insufficient SGRQ data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Day 337 | -4.726 Units on a scale | Standard Error 0.372 |
| Placebo | Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Day 337 | -1.787 Units on a scale | Standard Error 0.374 |
Secondary
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.
Time frame: Baseline and Day 169
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. 133 participants from the FAS were excluded due to insufficient FEV1 data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 169 | 0.121 Litres | Standard Error 0.006 |
| Placebo | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 169 | 0.018 Litres | Standard Error 0.006 |
Secondary
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.
Time frame: Baseline and Day 29
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. 147 participants from the FAS were excluded due to insufficient FEV1 data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29 | 0.11 Litres | Standard Error 0.005 |
| Placebo | Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29 | 0.017 Litres | Standard Error 0.005 |
Secondary
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.
Time frame: Baseline and Day 169
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. 133 participants from the FAS were excluded due to insufficient FVC data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 169 | 0.179 Litres | Standard Error 0.01 |
| Placebo | Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 169 | 0.019 Litres | Standard Error 0.01 |
Secondary
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.
Time frame: Baseline and Day 29
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. 147 participants from the FAS were excluded due to insufficient FVC data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 29 | 0.176 Litres | Standard Error 0.009 |
| Placebo | Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 29 | 0.025 Litres | Standard Error 0.009 |
Secondary
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.
Time frame: Baseline and Day 337
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. 133 participants from the FAS were excluded due to insufficient FVC data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 337 | 0.168 Litres | Standard Error 0.011 |
| Placebo | Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 337 | -0.001 Litres | Standard Error 0.011 |
Secondary
Clinically Relevant Findings in Physical Examination and ECG
Clinically relevant findings in Physical Examination and ECG at end of treatment
Time frame: End of treatment
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tiotropium | Clinically Relevant Findings in Physical Examination and ECG | ECG - new or worsened finding | 37 participants |
| Tiotropium | Clinically Relevant Findings in Physical Examination and ECG | ECG - No new/worsened finding | 1674 participants |
| Tiotropium | Clinically Relevant Findings in Physical Examination and ECG | ECG - Missing | 241 participants |
| Tiotropium | Clinically Relevant Findings in Physical Examination and ECG | Phys. Exam - No new/worsened finding | 1723 participants |
| Tiotropium | Clinically Relevant Findings in Physical Examination and ECG | Phys. Exam - Missing | 207 participants |
| Tiotropium | Clinically Relevant Findings in Physical Examination and ECG | Phys. Exam - new or worsened finding | 22 participants |
| Placebo | Clinically Relevant Findings in Physical Examination and ECG | ECG - Missing | 249 participants |
| Placebo | Clinically Relevant Findings in Physical Examination and ECG | Phys. Exam - new or worsened finding | 17 participants |
| Placebo | Clinically Relevant Findings in Physical Examination and ECG | Phys. Exam - Missing | 215 participants |
| Placebo | Clinically Relevant Findings in Physical Examination and ECG | ECG - No new/worsened finding | 1677 participants |
| Placebo | Clinically Relevant Findings in Physical Examination and ECG | ECG - new or worsened finding | 39 participants |
| Placebo | Clinically Relevant Findings in Physical Examination and ECG | Phys. Exam - No new/worsened finding | 1733 participants |
Secondary
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.
Time frame: Baseline and end of treatment
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tiotropium | Marked Changes From Baseline in Vital Signs at End of Treatment | SBP - Increase | 29 participants |
| Tiotropium | Marked Changes From Baseline in Vital Signs at End of Treatment | SBP - Decrease | 6 participants |
| Tiotropium | Marked Changes From Baseline in Vital Signs at End of Treatment | DBP - Decrease | 9 participants |
| Tiotropium | Marked Changes From Baseline in Vital Signs at End of Treatment | PR - Increase | 35 participants |
| Tiotropium | Marked Changes From Baseline in Vital Signs at End of Treatment | DBP - Increase | 40 participants |
| Tiotropium | Marked Changes From Baseline in Vital Signs at End of Treatment | PR - Decrease | 26 participants |
| Placebo | Marked Changes From Baseline in Vital Signs at End of Treatment | DBP - Decrease | 14 participants |
| Placebo | Marked Changes From Baseline in Vital Signs at End of Treatment | SBP - Increase | 31 participants |
| Placebo | Marked Changes From Baseline in Vital Signs at End of Treatment | PR - Decrease | 26 participants |
| Placebo | Marked Changes From Baseline in Vital Signs at End of Treatment | SBP - Decrease | 12 participants |
| Placebo | Marked Changes From Baseline in Vital Signs at End of Treatment | DBP - Increase | 39 participants |
| Placebo | Marked Changes From Baseline in Vital Signs at End of Treatment | PR - Increase | 43 participants |
Secondary
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)
Time frame: During actual study treatment period (planned Day 1 to Day 337)
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Number of COPD Exacerbations Per Patient - Exposure Adjusted | 0 COPD exacerbations per year | Full Range 0 |
| Placebo | Number of COPD Exacerbations Per Patient - Exposure Adjusted | 0 COPD exacerbations per year | Full Range 0 |
Secondary
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)
Time frame: During actual study treatment period (planned Day 1 to Day 337)
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Number of COPD Exacerbations Per Patient - naïve Estimate | 0 COPD exacerbations | Full Range 0 |
| Placebo | Number of COPD Exacerbations Per Patient - naïve Estimate | 0 COPD exacerbations | Full Range 0 |
Secondary
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)
Time frame: During actual study treatment period (planned Day 1 to Day 337)
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Number of Hospitalisations for COPD Exacerbations Per Patient - Exposure Adjusted | 0 hospitalisations for COPD exacerbations | Full Range 0 |
| Placebo | Number of Hospitalisations for COPD Exacerbations Per Patient - Exposure Adjusted | 0 hospitalisations for COPD exacerbations | Full Range 0 |
Secondary
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)
Time frame: During actual study treatment period (planned Day 1 to Day 337)
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Tiotropium | Number of Hospitalisations for COPD Exacerbations Per Patient - naïve Estimate | 0 hospitalisations for COPD exacerbations | Full Range 0 |
| Placebo | Number of Hospitalisations for COPD Exacerbations Per Patient - naïve Estimate | 0 hospitalisations for COPD exacerbations | Full Range 0 |
Secondary
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)
Time frame: During actual study treatment period (planned Day 1 to Day 337)
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tiotropium | Number of Patients With at Least One COPD Exacerbation | 685 participants |
| Placebo | Number of Patients With at Least One COPD Exacerbation | 842 participants |
Secondary
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)
Time frame: During actual study treatment period (planned Day 1 to Day 337)
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tiotropium | Number of Patients With at Least One Hospitalisation for a COPD Exacerbation | 161 participants |
| Placebo | Number of Patients With at Least One Hospitalisation for a COPD Exacerbation | 198 participants |
Secondary
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
Time frame: During actual study treatment period (planned Day 1 to Day 337)
Population: The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tiotropium | Time to First Hospitalisation for COPD Exacerbation | NA Days |
| Placebo | Time to First Hospitalisation for COPD Exacerbation | NA Days |