Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
The primary objective of this trial is to determine whether daily treatment with tiotropium (Spiriva®, Bromuro de Tiotropio®) inhalation capsule via HandiHaler® reduces the rate of decline in lung function over time in patients with COPD.
Interventions
DRUGtiotropium
DRUGplacebo
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
* Written informed consent. * Male or female patients 40 years of age or older. * Smoking history of at least 10 pack years. * Diagnosis of COPD with post bronchodilator FEV1 less than or equal to 70% of predicted normal and FEV1\<70% of FVC and on stable respiratory medication.
Exclusion criteria
* Significant diseases other than COPD which in the opinion of the investigator may put the patient at risk or influence the patients ability to participate. * Myocardial infarction in past 6 months. * Unstable or life threatening arrhythmia in past year. * Hospitalization for NYHA heart failure class III or IV in past year. * Active tuberculosis. * Asthma. * Pulmonary resection. * Malignancy treated with radiation or chemotherapy in past 5 years. * Respiratory infection in 4 weeks prior to screening. * Known hypersensitivity to anticholinergic drugs or components. * Known moderate to severe renal impairment. * Known narrow angle glaucoma. * Significant symptomatic BPH or bladder neck obstruction. * Need for oxygen therapy \>12 hr/day. * Use of oral corticosteroids at unstable doses or \>10 mg/day.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 30 to 4 Years | From day 30 to 4 years | Rate of decline of forced expiratory volume in one second (FEV1) measured before the use of bronchodilators. A negative rate of decline indicates decreasing FEV1 over time, while a positive value indicates increasing FEV1. |
| Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 30 to 4 Years | From day 30 to 4 years | Rate of decline of forced expiratory volume in one second (FEV1) measured after bronchodilation. A negative rate of decline indicates decreasing FEV1 over time, while a positive value indicates increasing FEV1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 12 | Month 12 | * SGRQ total score summarizes the impact of COPD on overall patient's health status. * Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. * The scale is continuous. * Rate of decline shows the yearly change of SGRQ total score. |
| Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 48 | Month 48 | — |
| Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 48 | Month 48 | — |
| Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 6 | Month 6 | * SGRQ total score summarizes the impact of COPD on overall patient's health status. * Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. * The scale is continuous. * Rate of decline shows the yearly change of SGRQ total score. |
| Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 18 | Month 18 | * SGRQ total score summarizes the impact of COPD on overall patient's health status. * Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. * The scale is continuous. * Rate of decline shows the yearly change of SGRQ total score. |
| Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 24 | Month 24 | * SGRQ total score summarizes the impact of COPD on overall patient's health status. * Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. * The scale is continuous. * Rate of decline shows the yearly change of SGRQ total score. |
| Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 30 | Month 30 | * SGRQ total score summarizes the impact of COPD on overall patient's health status. * Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. * The scale is continuous. * Rate of decline shows the yearly change of SGRQ total score. |
| Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 36 | Month 36 | * SGRQ total score summarizes the impact of COPD on overall patient's health status. * Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. * The scale is continuous. * Rate of decline shows the yearly change of SGRQ total score. |
| Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 42 | Month 42 | * SGRQ total score summarizes the impact of COPD on overall patient's health status. * Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. * The scale is continuous. * Rate of decline shows the yearly change of SGRQ total score. |
| Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 48 | Month 48 | * SGRQ total score summarizes the impact of COPD on overall patient's health status. * Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. * The scale is continuous. * Rate of decline shows the yearly change of SGRQ total score. |
| Number and Percentage of Participants With All Cause Death and Time to Event Analysis (On-treatment) | Day 1 to completion of double blinded treatment plus 30 days between Day 1 and 4 years plus 30 days | On-treatment defined as day 1 to completion of double blinded treatment plus 30 days |
| Number and Percentage of Participants With All Cause Death (Including Vital Status Follow-up, Cutoff at 1470 Days) | Day 1 to day 1470 | All cause mortality vital status information was followed-up after discontinuation; vital status information up to 1470 days after the start of treatment was used. |
| Number and Percentage of Participants With Lower Respiratory Death (On-treatment; Adjudicated Primary Cause) | Day 1 to completion of double blinded treatment plus 30 days between Day 1 and 4 years plus 30 days | The primary cause of death was adjudicated by an external committee prior to unblinding; on-treatment defined as day 1 to completion of double blinded treatment plus 30 days |
| Number and Percentage of Participants With a Lower Respiratory Death (Adjudicated; Including Vital Status Follow-up, Cutoff at 1470 Days) | Day 1 to day 1470 | The primary cause of death was adjudicated by an external committee prior to unblinding; vital status was information followed-up after discontinuation; vital status information up to 1470 days after the start of treatment was used |
| Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 18 | Month 18 | — |
| Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 24 | Month 24 | — |
| Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 24 | Month 24 | — |
| Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 30 | Month 30 | — |
| Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 30 | Month 30 | — |
| Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days. | Rate of decline of forced expiratory volume in one second (FEV1) measured before the use of bronchodilators. A negative rate of decline indicates decreasing FEV1 over time, while a positive value indicates increasing FEV1 |
| Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days | Rate of decline of forced expiratory volume in one second (FEV1) measured after the use of bronchodilators. A negative rate of decline indicates decreasing FEV1 over time, while a positive value indicates increasing FEV1 |
| Pre-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 30 to 4 Years | From day 30 to 4 years | Rate of decline of forced vital capacity (FVC) measured before the use of bronchodilators. A negative rate of decline indicates decreasing FVC over time, while a positive value indicates increasing FVC |
| Post-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 30 to 4 Years | From day 30 to 4 years | Rate of decline of forced vital capacity (FVC) measured after bronchodilation. A negative rate of decline indicates decreasing FVC over time, while a positive value indicates increasing FVC |
| Pre-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 30 to 4 Years | From day 30 to 4 years | Rate of decline of slow vital capacity (SVC) measured before the use of bronchodilators. A negative rate of decline indicates decreasing SVC over time, while a positive value indicates increasing SVC |
| Post-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 30 to 4 Years | From day 30 to 4 years | Rate of decline of slow vital capacity (SVC) measured after bronchodilation. A negative rate of decline indicates decreasing SVC over time, while a positive value indicates increasing SVC |
| Rate of Decline of St George's Respiratory Questionnaire (SGRQ) Total Score | From month 6 to 4 years | SGRQ total score shows the impact of COPD on patient's health status, and expressed as a percentage of impairment with scale from 0 (best health status) to 100 (worst possible status). A negative rate of decline shows decreasing SGRQ total score (or improved health) over time, while a positive value shows increasing score (or worsen health). |
| Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 18 | Month 18 | — |
| Pre-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days. | Rate of decline of forced vital capacity (FVC) before bronchodilation. A negative rate of decline indicates decreasing FVC over time, while a positive value indicates increasing FVC |
| Post-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days | Rate of decline of forced vital capacity (FVC) after bronchodilation. A negative rate of decline indicates decreasing FVC over time, while a positive value indicates increasing FVC |
| Pre-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days | Rate of decline slow vital capacity (SVC) before bronchodilation. A negative rate of decline indicates decreasing SVC over time, while a positive value indicates increasing SVC |
| Post-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days | Rate of decline of slow vital capacity (SVC) after bronchodilation. A negative rate of decline indicates decreasing SVC over time, while a positive value indicates increasing SVC |
| Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 36 | Month 36 | — |
| Time to First Exacerbation | From Day 1 to 4 years | Chronic obstructive pulmonary disease (COPD) exacerbation |
| Number of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Per Patient Year | Day 1 to 4 years | — |
| Number and Percentage of Patients With at Least One Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Day 1 to 4 years | — |
| Number of Exacerbation Days Per Patient Year | Day 1 to 4 years | Number of exacerbation days normalized by treatment exposure |
| Time to First COPD Exacerbation Leading to Hospitalization (for 25% Patients) | Day 1 to 4 years | — |
| Number and Percentage of Patients With at Least on COPD Exacerbation Leading to Hospitalization | From Day 1 to 4 years | — |
| Number of Exacerbation Leading to Hospitalization | From Day 1 to 4 years | Estimated number of exacerbations leading to hospitalizations per patient year |
| Days of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization | From Day 1 to 4 years | Number of days with chronic obstructive pulmonary disease (COPD) exacerbation leading to hospitalization (normalized by treatment exposure) |
| Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 1 | Month 1 | Estimated FEV1 before bronchodilator at Month 1 |
| Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 1 | Month 1 | Estimated forced expiratory volume in one second (FEV1) after bronchodilator at month 1 |
| Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 6 | Month 6 | Estimated forced expiratory volume in one second (FEV1) before bronchodilator at month 6 |
| Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 6 | Month 6 | — |
| Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 12 | Month 12 | — |
| Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 12 | Month 12 | — |
| Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 18 | Month 18 | — |
| Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 18 | Month 18 | — |
| Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 24 | Month 24 | — |
| Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 24 | Month 24 | — |
| Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 30 | Month 30 | — |
| Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 30 | Month 30 | — |
| Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 36 | Month 36 | — |
| Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 36 | Month 36 | — |
| Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 42 | Month 42 | — |
| Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 42 | Month 42 | Estimated FEV1 after bronchodilator at Month 42 |
| Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 48 | Month 48 | — |
| Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 48 | Month 48 | — |
| Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 1 | Month 1 | — |
| Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 1 | Month 1 | — |
| Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 6 | Month 6 | — |
| Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 6 | Month 6 | — |
| Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 12 | Month 12 | — |
| Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 12 | Month 12 | — |
| Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 36 | Month 36 | — |
| Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 42 | Month 42 | — |
| Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 42 | Month 42 | — |
| Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 48 | Month 48 | — |
| Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 48 | Month 48 | — |
| Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 1 | Month 1 | — |
| Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 1 | Month 1 | — |
| Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 6 | Month 6 | — |
| Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 6 | Month 6 | — |
| Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 12 | Month 12 | — |
| Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 12 | Month 12 | — |
| Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 18 | Month 18 | — |
| Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 18 | Month 18 | — |
| Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 24 | Month 24 | — |
| Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 24 | Month 24 | — |
| Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 30 | Month 30 | — |
| Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 30 | Month 30 | — |
| Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 36 | Month 36 | — |
| Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 36 | Month 36 | — |
| Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 42 | Month 42 | — |
| Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 42 | Month 42 | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of Serious Adverse Event (Preferred Term = Cardiac Failure) | Day 1 to completion of double blinded treatment plus 30 days | Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100. |
| Incidence Rate of Serious Adverse Event (Preferred Term = Cardiac Failure Congestive) | Day 1 to completion of double blinded treatment plus 30 days | Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100. |
| Incidence Rate of Serious Adverse Event (Preferred Term = Coronary Artery Disease) | Day 1 to completion of double blinded treatment plus 30 days | Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100. |
| Incidence Rate of Serious Adverse Event (Preferred Term = Myocardial Infarction) | Day 1 to completion of double blinded treatment plus 30 days | Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100. |
| Incidence Rate of Serious Adverse Event (System Organ Class = Lower Respiratory System Disorders) | Day 1 to completion of double blinded treatment plus 30 days | Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100. |
| Incidence Rate of Serious Adverse Event (Preferred Term = Bronchitis) | Day 1 to completion of double blinded treatment plus 30 days | Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100. |
| Incidence Rate of Serious Adverse Event (Preferred Term = Chronic Obstructive Pulmonary Disease (COPD) Exacerbation) | Day 1 to completion of double blinded treatment plus 30 days | Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100. |
| Incidence Rate of Serious Adverse Event (Preferred Term = Dyspnoea) | Day 1 to completion of double blinded treatment plus 30 days | Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100. |
| Incidence Rate of Serious Adverse Event (Preferred Term = Pneumonia) | Day 1 to completion of double blinded treatment plus 30 days | Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100. |
| Incidence Rate of Serious Adverse Event (Preferred Term = Respiratory Failure) | Day 1 to completion of double blinded treatment plus 30 days | Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100. |
| Incidence Rate of Serious Adverse Event (Preferred Term = Atrial Fibrillation) | Day 1 to completion of double blinded treatment plus 30 days | Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100. |
| Incidence Rate of Serious Adverse Event (Preferred Term = Angina) | Day 1 to completion of double blinded treatment plus 30 days | Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100. |
| Incidence Rate of Serious Adverse Event (System Organ Class = Cardiac Disorders) | Day 1 to completion of double blinded treatment plus 30 days | Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Czechia, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, Ireland, Italy, Japan, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Norway, Philippines, Poland, Portugal, Russia, Singapore, Slovakia, Slovenia, South Africa, Spain, Switzerland, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
09 Jan 2003 - 22 Feb 2008; 490 centers in 37 countries
Participants by arm
| Arm | Count |
|---|---|
| Placebo Once daily | 3,006 |
| Tiotropium Bromide Inhalation Capsules 18 mcg Once daily | 2,986 |
| Total | 5,992 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 746 | 627 |
| Overall Study | Lost to Follow-up | 76 | 64 |
| Overall Study | Other | 58 | 60 |
| Overall Study | Protocol Violation | 75 | 48 |
| Overall Study | Withdrawal by Subject | 403 | 300 |
Baseline characteristics
| Characteristic | Placebo | Tiotropium Bromide Inhalation Capsules 18 mcg | Total |
|---|---|---|---|
| Age, Continuous | 64.52 years STANDARD_DEVIATION 8.48 | 64.50 years STANDARD_DEVIATION 8.41 | 64.51 years STANDARD_DEVIATION 8.45 |
| Sex: Female, Male Female | 784 Participants | 735 Participants | 1519.0 Participants |
| Sex: Female, Male Male | 2222 Participants | 2251 Participants | 4473.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2,622 / — | 2,643 / — |
| serious Total, serious adverse events | 1,509 / — | 1,540 / — |
Outcome results
Primary
Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 30 to 4 Years
Rate of decline of forced expiratory volume in one second (FEV1) measured after bronchodilation. A negative rate of decline indicates decreasing FEV1 over time, while a positive value indicates increasing FEV1.
Time frame: From day 30 to 4 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 30 to 4 Years | -42 ml/year | Standard Error 1 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 30 to 4 Years | -40 ml/year | Standard Error 1 |
Comparison: Linear random effects modelp-value: 0.207495% CI: [-2, 6]t-test, 2 sided
Primary
Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 30 to 4 Years
Rate of decline of forced expiratory volume in one second (FEV1) measured before the use of bronchodilators. A negative rate of decline indicates decreasing FEV1 over time, while a positive value indicates increasing FEV1.
Time frame: From day 30 to 4 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 30 to 4 Years | -30 ml/year | Standard Error 1 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 30 to 4 Years | -30 ml/year | Standard Error 1 |
Comparison: Linear random effects modelp-value: 0.952495% CI: [-4, 4]t-test, 2 sided
Secondary
Days of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization
Number of days with chronic obstructive pulmonary disease (COPD) exacerbation leading to hospitalization (normalized by treatment exposure)
Time frame: From Day 1 to 4 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Days of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization | 3.13 days/patient year | Standard Error 0.17 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Days of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization | 3.17 days/patient year | Standard Error 0.17 |
Comparison: Poisson regression adjusting for overdispersion with Pearson's method adjusting for treatment exposure. The logarithm of treatment exposure is used as offset when building the Poisson model.p-value: 0.862495% CI: [0.87, 1.18]t-test, 2 sided
Secondary
Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 1
Estimated forced expiratory volume in one second (FEV1) after bronchodilator at month 1
Time frame: Month 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 1 | 1.372 L | Standard Error 0.004 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 1 | 1.418 L | Standard Error 0.004 |
p-value: <0.000195% CI: [0.037, 0.057]ANOVA
Secondary
Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 12
Time frame: Month 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 12 | 1.345 L | Standard Error 0.004 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 12 | 1.398 L | Standard Error 0.004 |
p-value: <0.000195% CI: [0.042, 0.065]ANOVA
Secondary
Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 18
Time frame: Month 18
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 18 | 1.326 L | Standard Error 0.005 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 18 | 1.379 L | Standard Error 0.005 |
p-value: <0.000195% CI: [0.04, 0.066]ANOVA
Secondary
Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 24
Time frame: Month 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 24 | 1.294 L | Standard Error 0.005 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 24 | 1.356 L | Standard Error 0.005 |
p-value: <0.000195% CI: [0.049, 0.075]ANOVA
Secondary
Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 30
Time frame: Month 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 30 | 1.274 L | Standard Error 0.005 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 30 | 1.335 L | Standard Error 0.005 |
p-value: <0.000195% CI: [0.047, 0.075]ANOVA
Secondary
Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 36
Time frame: Month 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 36 | 1.250 L | Standard Error 0.005 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 36 | 1.315 L | Standard Error 0.005 |
p-value: <0.000195% CI: [0.051, 0.08]ANOVA
Secondary
Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 42
Estimated FEV1 after bronchodilator at Month 42
Time frame: Month 42
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 42 | 1.236 L | Standard Error 0.006 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 42 | 1.297 L | Standard Error 0.005 |
p-value: <0.000195% CI: [0.045, 0.076]ANOVA
Secondary
Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 48
Time frame: Month 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 48 | 1.219 L | Standard Error 0.006 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 48 | 1.268 L | Standard Error 0.006 |
p-value: <0.000195% CI: [0.033, 0.065]ANOVA
Secondary
Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 6
Time frame: Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 6 | 1.365 L | Standard Deviation 0.004 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 6 | 1.423 L | Standard Deviation 0.004 |
p-value: <0.000195% CI: [0.047, 0.069]ANOVA
Secondary
Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 1
Time frame: Month 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 1 | 3.149 L | Standard Error 0.007 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 1 | 3.204 L | Standard Error 0.006 |
p-value: <0.000195% CI: [0.037, 0.073]ANOVA
Secondary
Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 12
Time frame: Month 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 12 | 3.110 L | Standard Error 0.008 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 12 | 3.158 L | Standard Error 0.008 |
p-value: <0.000195% CI: [0.026, 0.07]ANOVA
Secondary
Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 18
Time frame: Month 18
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 18 | 3.075 L | Standard Error 0.009 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 18 | 3.126 L | Standard Error 0.009 |
p-value: <0.000195% CI: [0.026, 0.074]ANOVA
Secondary
Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 24
Time frame: Month 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 24 | 3.036 L | Standard Error 0.009 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 24 | 3.095 L | Standard Error 0.009 |
p-value: <0.000195% CI: [0.035, 0.084]ANOVA
Secondary
Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 30
Time frame: Month 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 30 | 3.010 L | Standard Error 0.01 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 30 | 3.057 L | Standard Error 0.009 |
p-value: 0.000595% CI: [0.021, 0.074]ANOVA
Secondary
Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 36
Time frame: Month 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 36 | 2.973 L | Standard Error 0.01 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 36 | 3.038 L | Standard Error 0.01 |
p-value: <0.000195% CI: [0.038, 0.093]ANOVA
Secondary
Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 42
Time frame: Month 42
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 42 | 2.959 L | Standard Error 0.011 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 42 | 3.005 L | Standard Error 0.01 |
p-value: 0.00295% CI: [0.017, 0.076]ANOVA
Secondary
Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 48
Time frame: Month 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 48 | 2.929 L | Standard Error 0.011 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 48 | 2.961 L | Standard Error 0.01 |
p-value: 0.036595% CI: [0.002, 0.061]ANOVA
Secondary
Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 6
Time frame: Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 6 | 3.137 L | Standard Error 0.008 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 6 | 3.193 L | Standard Error 0.007 |
p-value: <0.000195% CI: [0.034, 0.076]ANOVA
Secondary
Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 1
Time frame: Month 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 1 | 3.280 L | Standard Error 0.007 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 1 | 3.318 L | Standard Error 0.007 |
p-value: 0.000295% CI: [0.018, 0.058]ANOVA
Secondary
Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 12
Time frame: Month 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 12 | 3.228 L | Standard Error 0.008 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 12 | 3.260 L | Standard Error 0.008 |
p-value: 0.006995% CI: [0.009, 0.055]ANOVA
Secondary
Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 18
Time frame: Month 18
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 18 | 3.195 L | Standard Error 0.009 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 18 | 3.234 L | Standard Error 0.009 |
p-value: 0.00295% CI: [0.015, 0.065]ANOVA
Secondary
Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 24
Time frame: Month 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 24 | 3.157 L | Standard Error 0.009 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 24 | 3.189 L | Standard Error 0.009 |
p-value: 0.016595% CI: [0.006, 0.057]ANOVA
Secondary
Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 30
Time frame: Month 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 30 | 3.126 L | Standard Error 0.01 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 30 | 3.157 L | Standard Error 0.01 |
p-value: 0.024895% CI: [0.004, 0.059]ANOVA
Secondary
Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 36
Time frame: Month 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 36 | 3.086 L | Standard Error 0.01 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 36 | 3.136 L | Standard Error 0.01 |
p-value: 0.000495% CI: [0.022, 0.078]ANOVA
Secondary
Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 42
Time frame: Month 42
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 42 | 3.073 L | Standard Error 0.011 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 42 | 3.100 L | Standard Error 0.011 |
p-value: 0.080995% CI: [-0.003, 0.057]ANOVA
Secondary
Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 48
Time frame: Month 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 48 | 3.041 L | Standard Error 0.011 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 48 | 3.067 L | Standard Error 0.011 |
p-value: 0.091595% CI: [-0.004, 0.057]ANOVA
Secondary
Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 6
Time frame: Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 6 | 3.268 L | Standard Error 0.008 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 6 | 3.304 L | Standard Error 0.008 |
p-value: 0.001895% CI: [0.014, 0.06]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 1
Estimated FEV1 before bronchodilator at Month 1
Time frame: Month 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 1 | 1.134 L | Standard Error 0.004 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 1 | 1.221 L | Standard Error 0.004 |
p-value: <0.000195% CI: [0.077, 0.098]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 12
Time frame: Month 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 12 | 1.111 L | Standard Error 0.004 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 12 | 1.213 L | Standard Error 0.004 |
p-value: <0.000195% CI: [0.091, 0.115]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 18
Time frame: Month 18
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 18 | 1.101 L | Standard Error 0.005 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 18 | 1.192 L | Standard Error 0.005 |
p-value: <0.000195% CI: [0.078, 0.104]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 24
Time frame: Month 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 24 | 1.079 L | Standard Error 0.005 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 24 | 1.173 L | Standard Error 0.005 |
p-value: <0.000195% CI: [0.081, 0.107]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 30
Time frame: Month 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 30 | 1.061 L | Standard Error 0.005 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 30 | 1.156 L | Standard Error 0.005 |
p-value: <0.000195% CI: [0.081, 0.109]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 36
Time frame: Month 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 36 | 1.045 L | Standard Error 0.005 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 36 | 1.144 L | Standard Error 0.005 |
p-value: <0.000195% CI: [0.085, 0.114]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 42
Time frame: Month 42
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 42 | 1.034 L | Standard Error 0.005 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 42 | 1.129 L | Standard Error 0.005 |
p-value: <0.000195% CI: [0.08, 0.11]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 48
Time frame: Month 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 48 | 1.024 L | Standard Error 0.006 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 48 | 1.112 L | Standard Error 0.005 |
p-value: <0.000195% CI: [0.073, 0.103]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 6
Estimated forced expiratory volume in one second (FEV1) before bronchodilator at month 6
Time frame: Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 6 | 1.126 L | Standard Error 0.004 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 6 | 1.225 L | Standard Error 0.004 |
p-value: <0.000195% CI: [0.087, 0.11]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 1
Time frame: Month 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 1 | 2.667 L | Standard Error 0.008 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 1 | 2.856 L | Standard Error 0.008 |
p-value: <0.000195% CI: [0.168, 0.211]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 12
Time frame: Month 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 12 | 2.640 L | Standard Error 0.009 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 12 | 2.838 L | Standard Error 0.009 |
p-value: <0.000195% CI: [0.173, 0.222]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 18
Time frame: Month 18
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 18 | 2.622 L | Standard Error 0.01 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 18 | 2.816 L | Standard Error 0.01 |
p-value: <0.000195% CI: [0.167, 0.221]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 24
Time frame: Month 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 24 | 2.597 L | Standard Error 0.01 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 24 | 2.785 L | Standard Error 0.01 |
p-value: <0.000195% CI: [0.161, 0.216]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 30
Time frame: Month 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 30 | 2.572 L | Standard Error 0.01 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 30 | 2.757 L | Standard Error 0.01 |
p-value: <0.000195% CI: [0.157, 0.213]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 36
Time frame: Month 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 36 | 2.553 L | Standard Error 0.011 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 36 | 2.753 L | Standard Error 0.01 |
p-value: <0.000195% CI: [0.17, 0.229]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 42
Time frame: Month 42
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 42 | 2.540 L | Standard Error 0.011 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 42 | 2.724 L | Standard Error 0.011 |
p-value: <0.000195% CI: [0.154, 0.215]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 48
Time frame: Month 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 48 | 2.532 L | Standard Error 0.011 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 48 | 2.702 L | Standard Error 0.011 |
p-value: <0.000195% CI: [0.139, 0.201]ANOVA
Secondary
Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 6
Time frame: Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 6 | 2.658 L | Standard Error 0.009 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 6 | 2.862 L | Standard Error 0.008 |
p-value: <0.000195% CI: [0.18, 0.228]ANOVA
Secondary
Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 1
Time frame: Month 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 1 | 2.847 L | Standard Error 0.008 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 1 | 3.017 L | Standard Error 0.008 |
p-value: <0.000195% CI: [0.147, 0.192]ANOVA
Secondary
Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 12
Time frame: Month 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 12 | 2.820 L | Standard Error 0.009 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 12 | 2.996 L | Standard Error 0.009 |
p-value: <0.000195% CI: [0.151, 0.201]ANOVA
Secondary
Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 18
Time frame: Month 18
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 18 | 2.811 L | Standard Error 0.01 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 18 | 2.965 L | Standard Error 0.01 |
p-value: <0.000195% CI: [0.127, 0.182]ANOVA
Secondary
Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 24
Time frame: Month 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 24 | 2.775 L | Standard Error 0.01 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 24 | 2.942 L | Standard Error 0.01 |
p-value: <0.000195% CI: [0.139, 0.194]ANOVA
Secondary
Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 30
Time frame: Month 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 30 | 2.738 L | Standard Error 0.011 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 30 | 2.908 L | Standard Error 0.01 |
p-value: <0.000195% CI: [0.141, 0.199]ANOVA
Secondary
Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 36
Time frame: Month 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 36 | 2.731 L | Standard Error 0.011 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 36 | 2.897 L | Standard Error 0.01 |
p-value: <0.000195% CI: [0.136, 0.196]ANOVA
Secondary
Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 42
Time frame: Month 42
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 42 | 2.713 L | Standard Error 0.011 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 42 | 2.875 L | Standard Error 0.011 |
p-value: <0.000195% CI: [0.13, 0.192]ANOVA
Secondary
Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 48
Time frame: Month 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 48 | 2.696 L | Standard Error 0.012 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 48 | 2.846 L | Standard Error 0.011 |
p-value: <0.000195% CI: [0.119, 0.182]ANOVA
Secondary
Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 6
Time frame: Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 6 | 2.841 L | Standard Error 0.009 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 6 | 3.027 L | Standard Error 0.009 |
p-value: <0.000195% CI: [0.161, 0.21]ANOVA
Secondary
Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 12
* SGRQ total score summarizes the impact of COPD on overall patient's health status. * Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. * The scale is continuous. * Rate of decline shows the yearly change of SGRQ total score.
Time frame: Month 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 12 | 42.501 Units on a scale | Standard Error 0.253 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 12 | 39.730 Units on a scale | Standard Error 0.245 |
p-value: <0.000195% CI: [-3.461, -2.081]ANOVA
Secondary
Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 18
* SGRQ total score summarizes the impact of COPD on overall patient's health status. * Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. * The scale is continuous. * Rate of decline shows the yearly change of SGRQ total score.
Time frame: Month 18
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 18 | 43.067 Units on a scale | Standard Error 0.278 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 18 | 40.474 Units on a scale | Standard Error 0.269 |
p-value: <0.000195% CI: [-3.352, -1.834]ANOVA
Secondary
Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 24
* SGRQ total score summarizes the impact of COPD on overall patient's health status. * Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. * The scale is continuous. * Rate of decline shows the yearly change of SGRQ total score.
Time frame: Month 24
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 24 | 43.562 Units on a scale | Standard Error 0.297 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 24 | 41.178 Units on a scale | Standard Error 0.286 |
p-value: <0.000195% CI: [-3.191, -1.576]ANOVA
Secondary
Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 30
* SGRQ total score summarizes the impact of COPD on overall patient's health status. * Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. * The scale is continuous. * Rate of decline shows the yearly change of SGRQ total score.
Time frame: Month 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 30 | 44.342 Units on a scale | Standard Error 0.315 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 30 | 41.919 Units on a scale | Standard Error 0.301 |
p-value: <0.000195% CI: [-3.277, -1.569]ANOVA
Secondary
Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 36
* SGRQ total score summarizes the impact of COPD on overall patient's health status. * Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. * The scale is continuous. * Rate of decline shows the yearly change of SGRQ total score.
Time frame: Month 36
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 36 | 45.280 Units on a scale | Standard Error 0.326 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 36 | 41.935 Units on a scale | Standard Error 0.311 |
p-value: <0.000195% CI: [-4.229, -2.462]ANOVA
Secondary
Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 42
* SGRQ total score summarizes the impact of COPD on overall patient's health status. * Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. * The scale is continuous. * Rate of decline shows the yearly change of SGRQ total score.
Time frame: Month 42
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 42 | 45.722 Units on a scale | Standard Error 0.342 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 42 | 42.905 Units on a scale | Standard Error 0.325 |
p-value: <0.000195% CI: [-3.742, -1.894]ANOVA
Secondary
Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 48
* SGRQ total score summarizes the impact of COPD on overall patient's health status. * Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. * The scale is continuous. * Rate of decline shows the yearly change of SGRQ total score.
Time frame: Month 48
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 48 | 45.968 Units on a scale | Standard Error 0.357 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 48 | 43.665 Units on a scale | Standard Error 0.338 |
p-value: <0.000195% CI: [-3.266, -1.34]ANOVA
Secondary
Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 6
* SGRQ total score summarizes the impact of COPD on overall patient's health status. * Total scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status. * The scale is continuous. * Rate of decline shows the yearly change of SGRQ total score.
Time frame: Month 6
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 6 | 42.289 Units on a scale | Standard Error 0.24 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Estimated St George's Respiratory Questionnaire (SGRQ) Total Score at Month 6 | 39.409 Units on a scale | Standard Error 0.233 |
p-value: <0.000195% CI: [-3.535, -2.226]ANOVA
Secondary
Number and Percentage of Participants With All Cause Death and Time to Event Analysis (On-treatment)
On-treatment defined as day 1 to completion of double blinded treatment plus 30 days
Time frame: Day 1 to completion of double blinded treatment plus 30 days between Day 1 and 4 years plus 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number and Percentage of Participants With All Cause Death and Time to Event Analysis (On-treatment) | Number of patients with on-treatment death | 402 Participants |
| Placebo | Number and Percentage of Participants With All Cause Death and Time to Event Analysis (On-treatment) | Percentage patients with on-treatment death | 13.4 Participants |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number and Percentage of Participants With All Cause Death and Time to Event Analysis (On-treatment) | Number of patients with on-treatment death | 374 Participants |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number and Percentage of Participants With All Cause Death and Time to Event Analysis (On-treatment) | Percentage patients with on-treatment death | 12.5 Participants |
p-value: 0.024295% CI: [0.74, 0.98]Log Rank
Secondary
Number and Percentage of Participants With All Cause Death (Including Vital Status Follow-up, Cutoff at 1470 Days)
All cause mortality vital status information was followed-up after discontinuation; vital status information up to 1470 days after the start of treatment was used.
Time frame: Day 1 to day 1470
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number and Percentage of Participants With All Cause Death (Including Vital Status Follow-up, Cutoff at 1470 Days) | Number of patients died from day 1 to day 1470 | 495 Participants |
| Placebo | Number and Percentage of Participants With All Cause Death (Including Vital Status Follow-up, Cutoff at 1470 Days) | Percentage of patients died from day 1 to day 1470 | 16.5 Participants |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number and Percentage of Participants With All Cause Death (Including Vital Status Follow-up, Cutoff at 1470 Days) | Number of patients died from day 1 to day 1470 | 446 Participants |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number and Percentage of Participants With All Cause Death (Including Vital Status Follow-up, Cutoff at 1470 Days) | Percentage of patients died from day 1 to day 1470 | 14.9 Participants |
p-value: 0.085995% CI: [0.79, 1.02]Log Rank
Secondary
Number and Percentage of Participants With a Lower Respiratory Death (Adjudicated; Including Vital Status Follow-up, Cutoff at 1470 Days)
The primary cause of death was adjudicated by an external committee prior to unblinding; vital status was information followed-up after discontinuation; vital status information up to 1470 days after the start of treatment was used
Time frame: Day 1 to day 1470
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number and Percentage of Participants With a Lower Respiratory Death (Adjudicated; Including Vital Status Follow-up, Cutoff at 1470 Days) | Number of patients with lower respiratory death | 173 Participants |
| Placebo | Number and Percentage of Participants With a Lower Respiratory Death (Adjudicated; Including Vital Status Follow-up, Cutoff at 1470 Days) | Percentage patients with lower respiratory death | 5.8 Participants |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number and Percentage of Participants With a Lower Respiratory Death (Adjudicated; Including Vital Status Follow-up, Cutoff at 1470 Days) | Number of patients with lower respiratory death | 153 Participants |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number and Percentage of Participants With a Lower Respiratory Death (Adjudicated; Including Vital Status Follow-up, Cutoff at 1470 Days) | Percentage patients with lower respiratory death | 5.1 Participants |
p-value: 0.237795% CI: [0.71, 1.09]Log Rank
Secondary
Number and Percentage of Participants With Lower Respiratory Death (On-treatment; Adjudicated Primary Cause)
The primary cause of death was adjudicated by an external committee prior to unblinding; on-treatment defined as day 1 to completion of double blinded treatment plus 30 days
Time frame: Day 1 to completion of double blinded treatment plus 30 days between Day 1 and 4 years plus 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number and Percentage of Participants With Lower Respiratory Death (On-treatment; Adjudicated Primary Cause) | Number of patients with lower respiratory | 140 Participants |
| Placebo | Number and Percentage of Participants With Lower Respiratory Death (On-treatment; Adjudicated Primary Cause) | Percentage of patients with lower respiratory | 4.7 Participants |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number and Percentage of Participants With Lower Respiratory Death (On-treatment; Adjudicated Primary Cause) | Number of patients with lower respiratory | 131 Participants |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number and Percentage of Participants With Lower Respiratory Death (On-treatment; Adjudicated Primary Cause) | Percentage of patients with lower respiratory | 4.4 Participants |
p-value: 0.193695% CI: [0.67, 1.08]Log Rank
Secondary
Number and Percentage of Patients With at Least on COPD Exacerbation Leading to Hospitalization
Time frame: From Day 1 to 4 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number and Percentage of Patients With at Least on COPD Exacerbation Leading to Hospitalization | Number of patients | 811 Participants |
| Placebo | Number and Percentage of Patients With at Least on COPD Exacerbation Leading to Hospitalization | Percentage of patients | 27 Participants |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number and Percentage of Patients With at Least on COPD Exacerbation Leading to Hospitalization | Number of patients | 759 Participants |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number and Percentage of Patients With at Least on COPD Exacerbation Leading to Hospitalization | Percentage of patients | 25.4 Participants |
Comparison: Cox regressionp-value: 0.002495% CI: [0.78, 0.95]Log Rank
Secondary
Number and Percentage of Patients With at Least One Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
Time frame: Day 1 to 4 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number and Percentage of Patients With at Least One Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Number of patients | 2049 Participants |
| Placebo | Number and Percentage of Patients With at Least One Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Percentage of patients | 68.2 Participants |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number and Percentage of Patients With at Least One Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Number of patients | 2001 Participants |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number and Percentage of Patients With at Least One Chronic Obstructive Pulmonary Disease (COPD) Exacerbation | Percentage of patients | 67 Participants |
p-value: 0.3481Fisher Exact
Secondary
Number of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Per Patient Year
Time frame: Day 1 to 4 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Number of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Per Patient Year | 0.85 number per patient year | Standard Error 0.02 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Per Patient Year | 0.73 number per patient year | Standard Error 0.02 |
Comparison: Poisson regression adjusted for overdispersion and treatment exposurep-value: <0.000195% CI: [0.81, 0.91]t-test, 2 sided
Secondary
Number of Exacerbation Days Per Patient Year
Number of exacerbation days normalized by treatment exposure
Time frame: Day 1 to 4 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Number of Exacerbation Days Per Patient Year | 13.64 days/patient year | Standard Error 0.35 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number of Exacerbation Days Per Patient Year | 12.11 days/patient year | Standard Error 0.32 |
Comparison: Poisson regression adjusted for overdispersion and treatment exposurep-value: 0.001195% CI: [0.83, 0.95]t-test, 2 sided
Secondary
Number of Exacerbation Leading to Hospitalization
Estimated number of exacerbations leading to hospitalizations per patient year
Time frame: From Day 1 to 4 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Exacerbation Leading to Hospitalization | 0.16 Number per patient year |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number of Exacerbation Leading to Hospitalization | 0.15 Number per patient year |
p-value: 0.341395% CI: [0.82, 1.07]t-test, 2 sided
Secondary
Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment
Rate of decline of forced expiratory volume in one second (FEV1) measured after the use of bronchodilators. A negative rate of decline indicates decreasing FEV1 over time, while a positive value indicates increasing FEV1
Time frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | -32 ml/year | Standard Error 2 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | -27 ml/year | Standard Error 2 |
p-value: 0.0145Wilcoxon Rank-sum test
Secondary
Post-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment
Rate of decline of forced vital capacity (FVC) after bronchodilation. A negative rate of decline indicates decreasing FVC over time, while a positive value indicates increasing FVC
Time frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Post-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | -40 ml/year | Standard Error 4 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Post-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | -40 ml/year | Standard Error 3 |
p-value: 0.306Wilcoxon Rank-sum test
Secondary
Post-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 30 to 4 Years
Rate of decline of forced vital capacity (FVC) measured after bronchodilation. A negative rate of decline indicates decreasing FVC over time, while a positive value indicates increasing FVC
Time frame: From day 30 to 4 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Post-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 30 to 4 Years | -61 ml/year | Standard Error 3 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Post-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 30 to 4 Years | -61 ml/year | Standard Error 3 |
Comparison: Linear random effects modelp-value: 0.837595% CI: [-9, 7]t-test, 2 sided
Secondary
Post-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment
Rate of decline of slow vital capacity (SVC) after bronchodilation. A negative rate of decline indicates decreasing SVC over time, while a positive value indicates increasing SVC
Time frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Post-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | -46 ml/year | Standard Error 4 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Post-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | -42 ml/year | Standard Error 3 |
p-value: 0.9814Wilcoxon Rank-sum test
Secondary
Post-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 30 to 4 Years
Rate of decline of slow vital capacity (SVC) measured after bronchodilation. A negative rate of decline indicates decreasing SVC over time, while a positive value indicates increasing SVC
Time frame: From day 30 to 4 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Post-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 30 to 4 Years | -65 ml/year | Standard Error 3 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Post-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 30 to 4 Years | -66 ml/year | Standard Error 3 |
Comparison: Linear random effects modelp-value: 0.78795% CI: [-9, 7]t-test, 2 sided
Secondary
Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment
Rate of decline of forced expiratory volume in one second (FEV1) measured before the use of bronchodilators. A negative rate of decline indicates decreasing FEV1 over time, while a positive value indicates increasing FEV1
Time frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | -17 ml/year | Standard Error 2 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | -15 ml/year | Standard Error 2 |
p-value: 0.2488Wilcoxon Rank-sum test
Secondary
Pre-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment
Rate of decline of forced vital capacity (FVC) before bronchodilation. A negative rate of decline indicates decreasing FVC over time, while a positive value indicates increasing FVC
Time frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Pre-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | -12 ml/year | Standard Error 4 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Pre-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | -10 ml/year | Standard Error 3 |
p-value: 0.2705Wilcoxon Rank-sum test
Secondary
Pre-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 30 to 4 Years
Rate of decline of forced vital capacity (FVC) measured before the use of bronchodilators. A negative rate of decline indicates decreasing FVC over time, while a positive value indicates increasing FVC
Time frame: From day 30 to 4 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pre-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 30 to 4 Years | -39 ml/year | Standard Error 3 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Pre-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 30 to 4 Years | -43 ml/year | Standard Error 3 |
Comparison: Linear random effects modelp-value: 0.29995% CI: [-12, 4]t-test, 2 sided
Secondary
Pre-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment
Rate of decline slow vital capacity (SVC) before bronchodilation. A negative rate of decline indicates decreasing SVC over time, while a positive value indicates increasing SVC
Time frame: Day 1 to 30 days after completion of double blinded treatment between Day 1 and 4 years plus 30 days
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Pre-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | -17 ml/year | Standard Error 4 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Pre-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment | -17 ml/year | Standard Error 4 |
p-value: 0.8103Wilcoxon Rank-sum test
Secondary
Pre-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 30 to 4 Years
Rate of decline of slow vital capacity (SVC) measured before the use of bronchodilators. A negative rate of decline indicates decreasing SVC over time, while a positive value indicates increasing SVC
Time frame: From day 30 to 4 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pre-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 30 to 4 Years | -41 ml/year | Standard Error 3 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Pre-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 30 to 4 Years | -47 ml/year | Standard Error 3 |
Comparison: Linear random effects modelp-value: 0.114395% CI: [-14, 2]t-test, 2 sided
Secondary
Rate of Decline of St George's Respiratory Questionnaire (SGRQ) Total Score
SGRQ total score shows the impact of COPD on patient's health status, and expressed as a percentage of impairment with scale from 0 (best health status) to 100 (worst possible status). A negative rate of decline shows decreasing SGRQ total score (or improved health) over time, while a positive value shows increasing score (or worsen health).
Time frame: From month 6 to 4 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Rate of Decline of St George's Respiratory Questionnaire (SGRQ) Total Score | 1.21 Score on scale per year | Standard Error 0.09 |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Rate of Decline of St George's Respiratory Questionnaire (SGRQ) Total Score | 1.25 Score on scale per year | Standard Error 0.09 |
Comparison: Linear random effects modelp-value: 0.78495% CI: [-0.2, 0.3]t-test, 2 sided
Secondary
Time to First COPD Exacerbation Leading to Hospitalization (for 25% Patients)
Time frame: Day 1 to 4 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First COPD Exacerbation Leading to Hospitalization (for 25% Patients) | 28.64 months |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Time to First COPD Exacerbation Leading to Hospitalization (for 25% Patients) | 35.89 months |
p-value: 0.1766Fisher Exact
Secondary
Time to First Exacerbation
Chronic obstructive pulmonary disease (COPD) exacerbation
Time frame: From Day 1 to 4 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to First Exacerbation | 12.51 months |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Time to First Exacerbation | 16.65 months |
Comparison: Cox regressionp-value: <0.000195% CI: [0.81, 0.91]Log Rank
Other Pre-specified
Incidence Rate of Serious Adverse Event (Preferred Term = Angina)
Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100.
Time frame: Day 1 to completion of double blinded treatment plus 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Angina) | Number of patients with event | 31 Number of patients with event |
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Angina) | Incidence rate (number events/100-patient years) | 0.36 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Angina) | Number of patients with event | 48 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Angina) | Incidence rate (number events/100-patient years) | 0.51 Number of patients with event |
p-value: 0.115895% CI: [0.91, 2.26]Z-test
Other Pre-specified
Incidence Rate of Serious Adverse Event (Preferred Term = Atrial Fibrillation)
Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100.
Time frame: Day 1 to completion of double blinded treatment plus 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Atrial Fibrillation) | Number of patients with event | 67 Number of patients with event |
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Atrial Fibrillation) | Incidence rate (number events/100-patient years) | 0.77 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Atrial Fibrillation) | Number of patients with event | 69 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Atrial Fibrillation) | Incidence rate (number events/100-patient years) | 0.74 Number of patients with event |
p-value: 0.772595% CI: [0.68, 1.33]Z-test
Other Pre-specified
Incidence Rate of Serious Adverse Event (Preferred Term = Bronchitis)
Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100.
Time frame: Day 1 to completion of double blinded treatment plus 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Bronchitis) | Number of patients with event | 27 Number of patients with event |
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Bronchitis) | Incidence rate (number events/100-patient years) | 0.31 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Bronchitis) | Number of patients with event | 35 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Bronchitis) | Incidence rate (number events/100-patient years) | 0.37 Number of patients with event |
p-value: 0.478995% CI: [0.73, 1.98]Z-test
Other Pre-specified
Incidence Rate of Serious Adverse Event (Preferred Term = Cardiac Failure)
Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100.
Time frame: Day 1 to completion of double blinded treatment plus 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Cardiac Failure) | Number of patients with event | 42 Number of patients with event |
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Cardiac Failure) | Incidence rate (number events/100-patient years) | 0.48 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Cardiac Failure) | Number of patients with event | 57 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Cardiac Failure) | Incidence rate (number events/100-patient years) | 0.61 Number of patients with event |
p-value: 0.266695% CI: [0.84, 1.87]Z-test
Other Pre-specified
Incidence Rate of Serious Adverse Event (Preferred Term = Cardiac Failure Congestive)
Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100.
Time frame: Day 1 to completion of double blinded treatment plus 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Cardiac Failure Congestive) | Number of patients with event | 42 Number of patients with event |
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Cardiac Failure Congestive) | Incidence rate (number events/100-patient years) | 0.48 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Cardiac Failure Congestive) | Number of patients with event | 27 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Cardiac Failure Congestive) | Incidence rate (number events/100-patient years) | 0.29 Number of patients with event |
p-value: 0.033795% CI: [0.37, 0.96]Z-test
Other Pre-specified
Incidence Rate of Serious Adverse Event (Preferred Term = Chronic Obstructive Pulmonary Disease (COPD) Exacerbation)
Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100.
Time frame: Day 1 to completion of double blinded treatment plus 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Chronic Obstructive Pulmonary Disease (COPD) Exacerbation) | Number of patients with event | 742 Number of patients with event |
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Chronic Obstructive Pulmonary Disease (COPD) Exacerbation) | Incidence rate (number events/100-patient years) | 9.70 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Chronic Obstructive Pulmonary Disease (COPD) Exacerbation) | Number of patients with event | 688 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Chronic Obstructive Pulmonary Disease (COPD) Exacerbation) | Incidence rate (number events/100-patient years) | 8.19 Number of patients with event |
p-value: 0.001495% CI: [0.76, 0.94]Z-test
Other Pre-specified
Incidence Rate of Serious Adverse Event (Preferred Term = Coronary Artery Disease)
Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100.
Time frame: Day 1 to completion of double blinded treatment plus 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Coronary Artery Disease) | Number of patients with event | 32 Number of patients with event |
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Coronary Artery Disease) | Incidence rate (number events/100-patient years) | 0.37 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Coronary Artery Disease) | Number of patients with event | 20 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Coronary Artery Disease) | Incidence rate (number events/100-patient years) | 0.21 Number of patients with event |
p-value: 0.053795% CI: [0.33, 1.01]Z-test
Other Pre-specified
Incidence Rate of Serious Adverse Event (Preferred Term = Dyspnoea)
Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100.
Time frame: Day 1 to completion of double blinded treatment plus 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Dyspnoea) | Number of patients with event | 54 Number of patients with event |
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Dyspnoea) | Incidence rate (number events/100-patient years) | 0.62 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Dyspnoea) | Number of patients with event | 36 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Dyspnoea) | Incidence rate (number events/100-patient years) | 0.38 Number of patients with event |
p-value: 0.023695% CI: [0.4, 0.94]Z-test
Other Pre-specified
Incidence Rate of Serious Adverse Event (Preferred Term = Myocardial Infarction)
Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100.
Time frame: Day 1 to completion of double blinded treatment plus 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Myocardial Infarction) | Number of patients with event | 84 Number of patients with event |
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Myocardial Infarction) | Incidence rate (number events/100-patient years) | 0.97 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Myocardial Infarction) | Number of patients with event | 65 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Myocardial Infarction) | Incidence rate (number events/100-patient years) | 0.69 Number of patients with event |
p-value: 0.040395% CI: [0.52, 0.99]Z-test
Other Pre-specified
Incidence Rate of Serious Adverse Event (Preferred Term = Pneumonia)
Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100.
Time frame: Day 1 to completion of double blinded treatment plus 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Pneumonia) | Number of patients with event | 290 Number of patients with event |
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Pneumonia) | Incidence rate (number events/100-patient years) | 3.46 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Pneumonia) | Number of patients with event | 296 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Pneumonia) | Incidence rate (number events/100-patient years) | 3.28 Number of patients with event |
p-value: 0.506495% CI: [0.81, 1.11]Z-test
Other Pre-specified
Incidence Rate of Serious Adverse Event (Preferred Term = Respiratory Failure)
Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100.
Time frame: Day 1 to completion of double blinded treatment plus 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Respiratory Failure) | Number of patients with event | 113 Number of patients with event |
| Placebo | Incidence Rate of Serious Adverse Event (Preferred Term = Respiratory Failure) | Incidence rate (number events/100-patient years) | 1.31 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Respiratory Failure) | Number of patients with event | 85 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (Preferred Term = Respiratory Failure) | Incidence rate (number events/100-patient years) | 0.90 Number of patients with event |
p-value: 0.010495% CI: [0.52, 0.92]Z-test
Other Pre-specified
Incidence Rate of Serious Adverse Event (System Organ Class = Cardiac Disorders)
Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100.
Time frame: Day 1 to completion of double blinded treatment plus 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence Rate of Serious Adverse Event (System Organ Class = Cardiac Disorders) | Number of patients with event | 350 Number of patients with event |
| Placebo | Incidence Rate of Serious Adverse Event (System Organ Class = Cardiac Disorders) | Incidence rate (number of events/100 patient year) | 4.21 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (System Organ Class = Cardiac Disorders) | Number of patients with event | 322 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (System Organ Class = Cardiac Disorders) | Incidence rate (number of events/100 patient year) | 3.56 Number of patients with event |
p-value: 0.02995% CI: [0.73, 0.98]Z-test
Other Pre-specified
Incidence Rate of Serious Adverse Event (System Organ Class = Lower Respiratory System Disorders)
Descriptive statistics show the number of patients with event, central tendency shows incidence rate. Incidence rate calculated as number of patients with event divided by at-risk years \* 100.
Time frame: Day 1 to completion of double blinded treatment plus 30 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Incidence Rate of Serious Adverse Event (System Organ Class = Lower Respiratory System Disorders) | Number of patients with event | 985 Number of patients with event |
| Placebo | Incidence Rate of Serious Adverse Event (System Organ Class = Lower Respiratory System Disorders) | Incidence rate (number events/100-patient years) | 13.47 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (System Organ Class = Lower Respiratory System Disorders) | Number of patients with event | 911 Number of patients with event |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Incidence Rate of Serious Adverse Event (System Organ Class = Lower Respiratory System Disorders) | Incidence rate (number events/100-patient years) | 11.32 Number of patients with event |
p-value: 0.000195% CI: [0.77, 0.92]Z-test
Post Hoc
Number and Percentage of Participants With All Cause Death (Including Vital Status Follow-up, Cutoff at 1440 Days)
Time frame: Day 1 to day 1440
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number and Percentage of Participants With All Cause Death (Including Vital Status Follow-up, Cutoff at 1440 Days) | Percentage of patients died from day 1 to day 1440 | 16.3 Participants |
| Placebo | Number and Percentage of Participants With All Cause Death (Including Vital Status Follow-up, Cutoff at 1440 Days) | Number of patients died from day 1 to day 1440 | 491 Participants |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number and Percentage of Participants With All Cause Death (Including Vital Status Follow-up, Cutoff at 1440 Days) | Number of patients died from day 1 to day 1440 | 430 Participants |
| Tiotropium Bromide Inhalation Capsules 18 mcg | Number and Percentage of Participants With All Cause Death (Including Vital Status Follow-up, Cutoff at 1440 Days) | Percentage of patients died from day 1 to day 1440 | 14.4 Participants |
Comparison: Hazard ratio of all cause mortality vital status was information followed-up after discontinuation; vital status information up to 1440 days after the start of treatment was usedp-value: 0.033995% CI: [0.76, 0.99]Log Rank