Evaluation of the Long- Term Effects of Spiriva on Lung Function in COPD Patients

• ClinicalTrials.gov Identifier: NCT00144339
• Recruitment Status: Completed
• First Posted: September 5, 2005
• Results First Posted: August 17, 2009
• Last Update Posted: May 20, 2014
• Sponsor: Boehringer Ingelheim
• Information provided by: Boehringer Ingelheim

• Study Type: Interventional
• Study Design: Intervention Model: Parallel Assignment; Primary Purpose: Treatment
• Condition: Pulmonary Disease, Chronic Obstructive
• Interventions: Drug: tiotropium; Drug: placebo
• Enrollment: 5993

Participant Flow

Recruitment Details	09 Jan 2003 - 22 Feb 2008; 490 centers in 37 countries
Pre-assignment Details

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description	once daily	once daily
Period Title: Overall Study
Started	3006	2986
Completed	1648	1887
Not Completed	1358	1099
Reason Not Completed
Adverse Event	746	627
Protocol Violation	75	48
Withdrawal by Subject	403	300
Lost to Follow-up	76	64
Other	58	60

Baseline Characteristics

Arm/Group Title		Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg	Total
Arm/Group Description		Once daily	Once daily	Total of all reporting groups
Overall Number of Baseline Participants		3006	2986	5992
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	3006 participants	2986 participants	5992 participants
		64.52 (8.48)	64.50 (8.41)	64.51 (8.45)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3006 participants	2986 participants	5992 participants
	Female	784 26.1%	735 24.6%	1519.0
	Male	2222 73.9%	2251 75.4%	4473.0

Outcome Measures

1. Primary Outcome

Title	Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 30 to 4 Years
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2413	2557
Mean (Standard Error); Unit of Measure: ml/year
	-30 (1)	-30 (1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	Linear random effects model
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9524
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	Random-effects model
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0
	Confidence Interval	95%; -4 to 4
	Parameter Dispersion	Type: Standard Error of the mean; Value: 2
	Estimation Comments	Arbitrary covariance matrix; fixed treatment effect; individual patients are random; rate of decline estimated as the slope of the random effects model

2. Primary Outcome

Title	Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 30 to 4 Years
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2410	2554
Mean (Standard Error); Unit of Measure: ml/year
	-42 (1)	-40 (1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	Linear random effects model
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2074
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	Random-effects model
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2
	Confidence Interval	95%; -2 to 6
	Parameter Dispersion	Type: Standard Error of the mean; Value: 2
	Estimation Comments	Arbitrary covariance matrix; fixed treatment effect; individual patients are random; rate of decline estimated as the slope of the random effects model

3. Secondary Outcome

Title	Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	1618	1803
Median (Standard Error); Unit of Measure: ml/year
	-17 (2)	-15 (2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2488
	Comments	[Not Specified]
	Method	Wilcoxon Rank-sum test
	Comments	Rate calculated as (measure on 30days after completion of treatment - measure on day 1 )/ years in between

4. Secondary Outcome

Title	Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	1613	1805
Median (Standard Error); Unit of Measure: ml/year
	-32 (2)	-27 (2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0145
	Comments	[Not Specified]
	Method	Wilcoxon Rank-sum test
	Comments	Rate calculated as (measure on 30days after completion of treatment - measure on day 1 )/ years in between

5. Secondary Outcome

Title	Pre-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 30 to 4 Years
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2413	2557
Mean (Standard Error); Unit of Measure: ml/year
	-39 (3)	-43 (3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	Linear random effects model
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2990
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4
	Confidence Interval	95%; -12 to 4
	Parameter Dispersion	Type: Standard Error of the mean; Value: 4
	Estimation Comments	Arbitrary covariance matrix; fixed treatment effect; individual patients are random; rate of decline estimated as the slope of the random effects model

6. Secondary Outcome

Title	Post-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 30 to 4 Years
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2410	2554
Mean (Standard Error); Unit of Measure: ml/year
	-61 (3)	-61 (3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	Linear random effects model
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8375
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1
	Confidence Interval	95%; -9 to 7
	Parameter Dispersion	Type: Standard Error of the mean; Value: 4
	Estimation Comments	Arbitrary covariance matrix; fixed treatment effect; individual patients are random; rate of decline estimated as the slope of the random effects model

7. Secondary Outcome

Title	Pre-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 30 to 4 Years
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2531
Mean (Standard Error); Unit of Measure: ml/year
	-41 (3)	-47 (3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	Linear random effects model
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1143
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-6
	Confidence Interval	95%; -14 to 2
	Parameter Dispersion	Type: Standard Error of the mean; Value: 4
	Estimation Comments	Arbitrary covariance matrix; fixed treatment effect; individual patients are random; rate of decline estimated as the slope of the random effects model

8. Secondary Outcome

Title	Post-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 30 to 4 Years
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2383	2527
Mean (Standard Error); Unit of Measure: ml/year
	-65 (3)	-66 (3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	Linear random effects model
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7870
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-1
	Confidence Interval	95%; -9 to 7
	Parameter Dispersion	Type: Standard Error of the mean; Value: 4
	Estimation Comments	Arbitrary covariance matrix; fixed treatment effect; individual patients are random; rate of decline estimated as the slope of the random effects model

9. Secondary Outcome

Title	Rate of Decline of St George's Respiratory Questionnaire (SGRQ) Total Score
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2362	2505
Mean (Standard Error); Unit of Measure: Score on scale per year
	1.21 (0.09)	1.25 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	Linear random effects model
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7840
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.04
	Confidence Interval	95%; -0.2 to 0.3
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.13
	Estimation Comments	Arbitrary covariance matrix; fixed treatment effect; individual patients are random; rate of decline estimated as the slope of the random effects model

10. Secondary Outcome

Title	Pre-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	1618	1803
Median (Standard Error); Unit of Measure: ml/year
	-12 (4)	-10 (3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2705
	Comments	[Not Specified]
	Method	Wilcoxon Rank-sum test
	Comments	Rate calculated as (measure on 30days after completion of treatment - measure on day 1 )/ years in between

11. Secondary Outcome

Title	Post-bronchodilator Forced Vital Capacity (FVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	1613	1805
Median (Standard Error); Unit of Measure: ml/year
	-40 (4)	-40 (3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.306
	Comments	[Not Specified]
	Method	Wilcoxon Rank-sum test
	Comments	Rate calculated as (measure on 30days after completion of treatment - measure on day 1 )/ years in between

12. Secondary Outcome

Title	Pre-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	1562	1706
Median (Standard Error); Unit of Measure: ml/year
	-17 (4)	-17 (4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8103
	Comments	[Not Specified]
	Method	Wilcoxon Rank-sum test
	Comments	Rate calculated as (measure on 30days after completion of treatment - measure on day 1 )/ years in between

13. Secondary Outcome

Title	Post-bronchodilator Slow Vital Capacity (SVC) Rate of Decline From Day 1 to 30 Days After Completion of Double Blinded Treatment
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	1540	1711
Median (Standard Error); Unit of Measure: ml/year
	-46 (4)	-42 (3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9814
	Comments	[Not Specified]
	Method	Wilcoxon Rank-sum test
	Comments	Rate calculated as (measure on 30days after completion of treatment - measure on day 1 )/ years in between

14. Secondary Outcome

Title	Time to First Exacerbation
Description	Chronic obstructive pulmonary disease (COPD) exacerbation
Time Frame	From Day 1 to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	3006	2986
Median (95% Confidence Interval); Unit of Measure: months
	12.51; (11.53 to 13.79)	16.65; (14.88 to 17.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	Cox regression
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Cox regression with treatment
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	95%; 0.81 to 0.91
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.03
	Estimation Comments	Median estimated by Kaplan-Meier estimates; hazard ratio shown as tio vs. placebo

15. Secondary Outcome

Title	Number of Chronic Obstructive Pulmonary Disease (COPD) Exacerbations Per Patient Year
Description	[Not Specified]
Time Frame	Day 1 to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	3006	2986
Mean (Standard Error); Unit of Measure: number per patient year
	0.85 (0.02)	0.73 (0.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	Poisson regression adjusted for overdispersion and treatment exposure
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.86
	Confidence Interval	95%; 0.81 to 0.91
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.03
	Estimation Comments	Ratio calculated as estimated number of events in tio/number of events in placebo

16. Secondary Outcome

Title	Number and Percentage of Patients With at Least One Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
Description	[Not Specified]
Time Frame	Day 1 to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	3006	2986
Measure Type: Number; Unit of Measure: Participants
Number of patients	2049	2001
Percentage of patients	68.2	67

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3481
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

17. Secondary Outcome

Title	Number of Exacerbation Days Per Patient Year
Description	Number of exacerbation days normalized by treatment exposure
Time Frame	Day 1 to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	3006	2986
Mean (Standard Error); Unit of Measure: days/patient year
	13.64 (0.35)	12.11 (0.32)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	Poisson regression adjusted for overdispersion and treatment exposure
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0011
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.89
	Confidence Interval	95%; 0.83 to 0.95
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.03
	Estimation Comments	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.

18. Secondary Outcome

Title	Time to First COPD Exacerbation Leading to Hospitalization (for 25% Patients)
Description	[Not Specified]
Time Frame	Day 1 to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	3006	2986
Median (95% Confidence Interval); Unit of Measure: months
	28.64; (26.08 to 31.82)	35.89; (23.38 to 39.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1766
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

19. Secondary Outcome

Title	Number and Percentage of Patients With at Least on COPD Exacerbation Leading to Hospitalization
Description	[Not Specified]
Time Frame	From Day 1 to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	3006	2986
Measure Type: Number; Unit of Measure: Participants
Number of patients	811	759
Percentage of patients	27	25.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	Cox regression
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0024
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	95%; 0.78 to 0.95
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.04
	Estimation Comments	Hazard ratio shown as tiotropium bromide vs. placebo

20. Secondary Outcome

Title	Number of Exacerbation Leading to Hospitalization
Description	Estimated number of exacerbations leading to hospitalizations per patient year
Time Frame	From Day 1 to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	3006	2986
Measure Type: Number; Unit of Measure: Number per patient year
	0.16	0.15

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.3413
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	0.94
	Confidence Interval	95%; 0.82 to 1.07
	Parameter Dispersion	Type: Standard Error of the mean; Value: 0.06
	Estimation Comments	Ratio of estimated number of events between tiotropium bromide and placebo

21. Secondary Outcome

Title	Days of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	3006	2986
Mean (Standard Error); Unit of Measure: days/patient year
	3.13 (0.17)	3.17 (0.17)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	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.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.8624
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Rate ratio
	Estimated Value	1.01
	Confidence Interval	95%; 0.87 to 1.18
	Estimation Comments	Ratio of estimated number of days of chronic obstructive pulmonary disease (COPD) exacerbation leading to hospitalization between tio and placebo

22. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 1
Description	Estimated FEV1 before bronchodilator at Month 1
Time Frame	Month 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	1.134 (0.004)	1.221 (0.004)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.087
	Confidence Interval	95%; 0.077 to 0.098
	Estimation Comments	[Not Specified]

23. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 1
Description	Estimated forced expiratory volume in one second (FEV1) after bronchodilator at month 1
Time Frame	Month 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	1.372 (0.004)	1.418 (0.004)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.047
	Confidence Interval	95%; 0.037 to 0.057
	Estimation Comments	[Not Specified]

24. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 6
Description	Estimated forced expiratory volume in one second (FEV1) before bronchodilator at month 6
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	1.126 (0.004)	1.225 (0.004)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.099
	Confidence Interval	95%; 0.087 to 0.110
	Estimation Comments	[Not Specified]

25. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 6
Description	[Not Specified]
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Deviation); Unit of Measure: L
	1.365 (0.004)	1.423 (0.004)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.058
	Confidence Interval	95%; 0.047 to 0.069
	Estimation Comments	[Not Specified]

26. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 12
Description	[Not Specified]
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	1.111 (0.004)	1.213 (0.004)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.103
	Confidence Interval	95%; 0.091 to 0.115
	Estimation Comments	[Not Specified]

27. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 12
Description	[Not Specified]
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	1.345 (0.004)	1.398 (0.004)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.054
	Confidence Interval	95%; 0.042 to 0.065
	Estimation Comments	[Not Specified]

28. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 18
Description	[Not Specified]
Time Frame	Month 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	1.101 (0.005)	1.192 (0.005)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.091
	Confidence Interval	95%; 0.078 to 0.104
	Estimation Comments	[Not Specified]

29. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 18
Description	[Not Specified]
Time Frame	Month 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	1.326 (0.005)	1.379 (0.005)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.053
	Confidence Interval	95%; 0.040 to 0.066
	Estimation Comments	[Not Specified]

30. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 24
Description	[Not Specified]
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	1.079 (0.005)	1.173 (0.005)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.094
	Confidence Interval	95%; 0.081 to 0.107
	Estimation Comments	[Not Specified]

31. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 24
Description	[Not Specified]
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	1.294 (0.005)	1.356 (0.005)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.062
	Confidence Interval	95%; 0.049 to 0.075
	Estimation Comments	[Not Specified]

32. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 30
Description	[Not Specified]
Time Frame	Month 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	1.061 (0.005)	1.156 (0.005)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.095
	Confidence Interval	95%; 0.081 to 0.109
	Estimation Comments	[Not Specified]

33. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 30
Description	[Not Specified]
Time Frame	Month 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	1.274 (0.005)	1.335 (0.005)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.061
	Confidence Interval	95%; 0.047 to 0.075
	Estimation Comments	[Not Specified]

34. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 36
Description	[Not Specified]
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	1.045 (0.005)	1.144 (0.005)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.099
	Confidence Interval	95%; 0.085 to 0.114
	Estimation Comments	[Not Specified]

35. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 36
Description	[Not Specified]
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	1.250 (0.005)	1.315 (0.005)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.065
	Confidence Interval	95%; 0.051 to 0.080
	Estimation Comments	[Not Specified]

36. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 42
Description	[Not Specified]
Time Frame	Month 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	1.034 (0.005)	1.129 (0.005)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.095
	Confidence Interval	95%; 0.080 to 0.110
	Estimation Comments	[Not Specified]

37. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 42
Description	Estimated FEV1 after bronchodilator at Month 42
Time Frame	Month 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	1.236 (0.006)	1.297 (0.005)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.061
	Confidence Interval	95%; 0.045 to 0.076
	Estimation Comments	[Not Specified]

38. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 48
Description	[Not Specified]
Time Frame	Month 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	1.024 (0.006)	1.112 (0.005)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.088
	Confidence Interval	95%; 0.073 to 0.103
	Estimation Comments	[Not Specified]

39. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Month 48
Description	[Not Specified]
Time Frame	Month 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	1.219 (0.006)	1.268 (0.006)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.049
	Confidence Interval	95%; 0.033 to 0.065
	Estimation Comments	[Not Specified]

40. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 1
Description	[Not Specified]
Time Frame	Month 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	2.667 (0.008)	2.856 (0.008)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.190
	Confidence Interval	95%; 0.168 to 0.211
	Estimation Comments	[Not Specified]

41. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 1
Description	[Not Specified]
Time Frame	Month 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	3.149 (0.007)	3.204 (0.006)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.055
	Confidence Interval	95%; 0.037 to 0.073
	Estimation Comments	[Not Specified]

42. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 6
Description	[Not Specified]
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	2.658 (0.009)	2.862 (0.008)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.204
	Confidence Interval	95%; 0.180 to 0.228
	Estimation Comments	[Not Specified]

43. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 6
Description	[Not Specified]
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	3.137 (0.008)	3.193 (0.007)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.055
	Confidence Interval	95%; 0.034 to 0.076
	Estimation Comments	[Not Specified]

44. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 12
Description	[Not Specified]
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	2.640 (0.009)	2.838 (0.009)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.198
	Confidence Interval	95%; 0.173 to 0.222
	Estimation Comments	[Not Specified]

45. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 12
Description	[Not Specified]
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	3.110 (0.008)	3.158 (0.008)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.048
	Confidence Interval	95%; 0.026 to 0.070
	Estimation Comments	[Not Specified]

46. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 18
Description	[Not Specified]
Time Frame	Month 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	2.622 (0.010)	2.816 (0.010)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.194
	Confidence Interval	95%; 0.167 to 0.221
	Estimation Comments	[Not Specified]

47. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 18
Description	[Not Specified]
Time Frame	Month 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	3.075 (0.009)	3.126 (0.009)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.050
	Confidence Interval	95%; 0.026 to 0.074
	Estimation Comments	[Not Specified]

48. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 24
Description	[Not Specified]
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	2.597 (0.010)	2.785 (0.010)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.189
	Confidence Interval	95%; 0.161 to 0.216
	Estimation Comments	[Not Specified]

49. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 24
Description	[Not Specified]
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	3.036 (0.009)	3.095 (0.009)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.059
	Confidence Interval	95%; 0.035 to 0.084
	Estimation Comments	[Not Specified]

50. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 30
Description	[Not Specified]
Time Frame	Month 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	2.572 (0.010)	2.757 (0.010)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.185
	Confidence Interval	95%; 0.157 to 0.213
	Estimation Comments	[Not Specified]

51. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 30
Description	[Not Specified]
Time Frame	Month 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	3.010 (0.010)	3.057 (0.009)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0005
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.047
	Confidence Interval	95%; 0.021 to 0.074
	Estimation Comments	[Not Specified]

52. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 36
Description	[Not Specified]
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	2.553 (0.011)	2.753 (0.010)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.200
	Confidence Interval	95%; 0.170 to 0.229
	Estimation Comments	[Not Specified]

53. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 36
Description	[Not Specified]
Time Frame	Month 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	2.973 (0.010)	3.038 (0.010)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.065
	Confidence Interval	95%; 0.038 to 0.093
	Estimation Comments	[Not Specified]

54. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 42
Description	[Not Specified]
Time Frame	Month 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	2.540 (0.011)	2.724 (0.011)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.184
	Confidence Interval	95%; 0.154 to 0.215
	Estimation Comments	[Not Specified]

55. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 42
Description	[Not Specified]
Time Frame	Month 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	2.959 (0.011)	3.005 (0.010)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0020
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.046
	Confidence Interval	95%; 0.017 to 0.076
	Estimation Comments	[Not Specified]

56. Secondary Outcome

Title	Estimated Pre-bronchodilator Forced Vital Capacity (FVC) at Month 48
Description	[Not Specified]
Time Frame	Month 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2363	2494
Mean (Standard Error); Unit of Measure: L
	2.532 (0.011)	2.702 (0.011)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.170
	Confidence Interval	95%; 0.139 to 0.201
	Estimation Comments	[Not Specified]

57. Secondary Outcome

Title	Estimated Post-bronchodilator Forced Vital Capacity (FVC) at Month 48
Description	[Not Specified]
Time Frame	Month 48

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2374	2516
Mean (Standard Error); Unit of Measure: L
	2.929 (0.011)	2.961 (0.010)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0365
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.032
	Confidence Interval	95%; 0.002 to 0.061
	Estimation Comments	[Not Specified]

58. Secondary Outcome

Title	Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 1
Description	[Not Specified]
Time Frame	Month 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2325	2447
Mean (Standard Error); Unit of Measure: L
	2.847 (0.008)	3.017 (0.008)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.170
	Confidence Interval	95%; 0.147 to 0.192
	Estimation Comments	[Not Specified]

59. Secondary Outcome

Title	Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 1
Description	[Not Specified]
Time Frame	Month 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2340	2467
Mean (Standard Error); Unit of Measure: L
	3.280 (0.007)	3.318 (0.007)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0002
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.038
	Confidence Interval	95%; 0.018 to 0.058
	Estimation Comments	[Not Specified]

60. Secondary Outcome

Title	Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 6
Description	[Not Specified]
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2325	2447
Mean (Standard Error); Unit of Measure: L
	2.841 (0.009)	3.027 (0.009)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.186
	Confidence Interval	95%; 0.161 to 0.210
	Estimation Comments	[Not Specified]

61. Secondary Outcome

Title	Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 6
Description	[Not Specified]
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2340	2467
Mean (Standard Error); Unit of Measure: L
	3.268 (0.008)	3.304 (0.008)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0018
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.037
	Confidence Interval	95%; 0.014 to 0.060
	Estimation Comments	[Not Specified]

62. Secondary Outcome

Title	Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 12
Description	[Not Specified]
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2325	2447
Mean (Standard Error); Unit of Measure: L
	2.820 (0.009)	2.996 (0.009)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.176
	Confidence Interval	95%; 0.151 to 0.201
	Estimation Comments	[Not Specified]

63. Secondary Outcome

Title	Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 12
Description	[Not Specified]
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2340	2467
Mean (Standard Error); Unit of Measure: L
	3.228 (0.008)	3.260 (0.008)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0069
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.032
	Confidence Interval	95%; 0.009 to 0.055
	Estimation Comments	[Not Specified]

64. Secondary Outcome

Title	Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 18
Description	[Not Specified]
Time Frame	Month 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2325	2447
Mean (Standard Error); Unit of Measure: L
	2.811 (0.010)	2.965 (0.010)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.154
	Confidence Interval	95%; 0.127 to 0.182
	Estimation Comments	[Not Specified]

65. Secondary Outcome

Title	Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 18
Description	[Not Specified]
Time Frame	Month 18

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2340	2467
Mean (Standard Error); Unit of Measure: L
	3.195 (0.009)	3.234 (0.009)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0020
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.040
	Confidence Interval	95%; 0.015 to 0.065
	Estimation Comments	[Not Specified]

66. Secondary Outcome

Title	Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 24
Description	[Not Specified]
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2325	2447
Mean (Standard Error); Unit of Measure: L
	2.775 (0.010)	2.942 (0.010)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.167
	Confidence Interval	95%; 0.139 to 0.194
	Estimation Comments	[Not Specified]

67. Secondary Outcome

Title	Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 24
Description	[Not Specified]
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2340	2467
Mean (Standard Error); Unit of Measure: L
	3.157 (0.009)	3.189 (0.009)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0165
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.032
	Confidence Interval	95%; 0.006 to 0.057
	Estimation Comments	[Not Specified]

68. Secondary Outcome

Title	Estimated Pre-bronchodilator Slow Vital Capacity (SVC) at Month 30
Description	[Not Specified]
Time Frame	Month 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2325	2447
Mean (Standard Error); Unit of Measure: L
	2.738 (0.011)	2.908 (0.010)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANOVA
	Comments	Repeated measures ANOVA
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.170
	Confidence Interval	95%; 0.141 to 0.199
	Estimation Comments	[Not Specified]

69. Secondary Outcome

Title	Estimated Post-bronchodilator Slow Vital Capacity (SVC) at Month 30
Description	[Not Specified]
Time Frame	Month 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Tiotropium Bromide Inhalation Capsules 18 mcg
Arm/Group Description:	Once daily	Once daily
Overall Number of Participants Analyzed	2340	2467
Mean (Standard Error); Unit of Measure: L
	3.126 (0.010)	3.157 (0.010)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Tiotropium Bromide Inhalation Capsules 18 mcg
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0248