Tiotropium / Respimat One Year Study in COPD.

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00387088
• Collaborator: (none)
• Enrollment: 3,991
• Locations: 334
• Arms: 2
• Patients Per Site: 11.9

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Device: Respimat; Drug: Tiotropium	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 3991 participants
• Intervention Model: Parallel Assignment
• Primary Purpose: Treatment
• Official Title: Efficacy {FEV1, COPD Exacerbations & HRQoL} & Safety of 5mcg Tiotropium Respimat in COPD
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Jan 1, 2009

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 337 [Baseline and Day 337]

   Trough FEV1 is defined as the FEV1 measured at the -10 min time point at the end of the dosing interval (24 h post drug administration).

2. Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation [During actual study treatment period (planned Day 1 to Day 337)]

   Time to first COPD exacerbation (defined as a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment). Time is days from start of study treatment to onset of exacerbation.

Secondary Outcome Measures

1. Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29 [Baseline and Day 29]

   Trough FEV1 is the mean volume of air that can be forced out in one second after taking a deep breath approximately 24 hours after the last administration of study drug.

2. Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 169 [Baseline and Day 169]

   Trough FEV1 is the mean volume of air that can be forced out in one second after taking a deep breath approximately 24 hours after the last administration of study drug.

3. Number of COPD Exacerbations Per Patient - Exposure Adjusted [During actual study treatment period (planned Day 1 to Day 337)]

   Number of COPD exacerbations (defined as a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment) per patient adjusted by length of treatment exposure (i.e. number of exacerbations multiplied by 365.25 and then divided by days of treatment exposure)

4. Number of COPD Exacerbations Per Patient - naïve Estimate [During actual study treatment period (planned Day 1 to Day 337)]

   Number of COPD exacerbations (defined as a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment) per patient not adjusted for treatment exposure (i.e. naïve estimate)

5. Number of Patients With at Least One COPD Exacerbation [During actual study treatment period (planned Day 1 to Day 337)]

   Number of patients with at least one COPD exacerbation (defined as a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment)

6. Time to First Hospitalisation for COPD Exacerbation [During actual study treatment period (planned Day 1 to Day 337)]

   Time to first hospitalisation for COPD exacerbation (a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment). Time is days from start of study treatment to onset of exacerbation

7. Number of Hospitalisations for COPD Exacerbations Per Patient - Exposure Adjusted [During actual study treatment period (planned Day 1 to Day 337)]

   Number of hospitalisations for COPD exacerbations (a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment) per patient adjusted by length of treatment exposure (i.e. no. of exacerbations multiplied by 365.25 and then divided by days of treatment exposure)

8. Number of Hospitalisations for COPD Exacerbations Per Patient - naïve Estimate [During actual study treatment period (planned Day 1 to Day 337)]

   Number of hospitalisations for COPD exacerbations (a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment) per patient not adjusted for treatment exposure (i.e. naïve estimate)

9. Number of Patients With at Least One Hospitalisation for a COPD Exacerbation [During actual study treatment period (planned Day 1 to Day 337)]

   Number of patients with at least one hospitalisation for a COPD exacerbation (a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment)

10. Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Day 337 [Baseline and Day 337]

    The SGRQ total score measures quality of life on a continuous scale ranging from 0=best state to 100=worst state

11. Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Day 169 [Baseline and Day 169]

    The SGRQ total score measures quality of life on a continuous scale ranging from 0=best state to 100=worst state

12. Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 337 [Baseline and Day 337]

    The SGRQ domain score (symptom, activity and impact) measures quality of life on a continuous scale ranging from 0=best state to 100=worst state

13. Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 169 [Baseline and Day 169]

    The SGRQ domain score (symptom, activity and impact) measures quality of life on a continuous scale ranging from 0=best state to 100=worst state

14. Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 29 [Baseline and Day 29]

    Trough FVC is the mean maximum volume of air that can be forcibly expired from the lungs; measured approximately 24 hours after the last administration of study drug.

15. Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 169 [Baseline and Day 169]

    Trough FVC is the mean maximum volume of air that can be forcibly expired from the lungs; measured approximately 24 hours after the last administration of study drug.

16. Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 337 [Baseline and Day 337]

    Trough FVC is the mean maximum volume of air that can be forcibly expired from the lungs; measured approximately 24 hours after the last administration of study drug.

17. Marked Changes From Baseline in Vital Signs at End of Treatment [Baseline and end of treatment]

    Marked changes from baseline in vital signs (diastolic and systolic blood pressure (DBP and SBP) and pulse rate (PR)) at end of treatment. SBP - Increase means SBP >150 mmHg and an increase above baseline of >25 mmHg. SBP - Decrease means SBP <100 mmHg and a decrease below baseline of >10 mmHg. DBP - Increase means DBP >90 mmHg and an increase above baseline of >10 mmHg. DBP - Decrease means DBP <60 mmHg and a decrease below baseline of >10 mmHg. PR - Increase means PR >100 bpm and an increase above baseline of >10 bpm. PR - Decrease means PR <60 bpm and a decrease below baseline of >10 bpm.

18. Clinically Relevant Findings in Physical Examination and ECG [End of treatment]

    Clinically relevant findings in Physical Examination and ECG at end of treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female

2. At least 40 years old

3. Smoker or ex-smoker

4. Smoking history > 10 pack-years

5. Forced Expiratory Volume in 1 Second (FEV1) < 60% predicted

Exclusion Criteria:

1. Recent history of myocardial infarction, life-threatening cardiac arrhythmia or hospitalisation for cardiac failure

2. History of asthma or allergic conditions.

3. Malignancy requiring treatment within past 5 years

4. Life-threatening pulmonary obstruction, cystic fibrosis or clinically evident bronchiectasis

5. Known active tuberculosis

6. Known hypersensitivity to anticholinergic drugs.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	205.372.01012 Boehringer Ingelheim Investigational Site	Birmingham	Alabama	United States
2	205.372.01020 Boehringer Ingelheim Investigational Site	Birmingham	Alabama	United States
3	205.372.01062 Boehringer Ingelheim Investigational Site	Mobile	Alabama	United States
4	205.372.01048 Boehringer Ingelheim Investigational Site	Berkeley	California	United States
5	205.372.01037 Boehringer Ingelheim Investigational Site	Huntington Park	California	United States
6	205.372.01058 Boehringer Ingelheim Investigational Site	Long Beach	California	United States
7	205.372.01059 Boehringer Ingelheim Investigational Site	Long Beach	California	United States
8	205.372.01007 Boehringer Ingelheim Investigational Site	Los Angeles	California	United States
9	205.372.01034 Boehringer Ingelheim Investigational Site	Los Angeles	California	United States
10	205.372.01028 Boehringer Ingelheim Investigational Site	Rancho Mirage	California	United States
11	205.372.01011 Boehringer Ingelheim Investigational Site	San Diego	California	United States
12	205.372.01066 Boehringer Ingelheim Investigational Site	Boulder	Colorado	United States
13	205.372.01008 Boehringer Ingelheim Investigational Site	Norwalk	Connecticut	United States
14	205.372.01004 Boehringer Ingelheim Investigational Site	Brandon	Florida	United States
15	205.372.01060 Boehringer Ingelheim Investigational Site	Clearwater	Florida	United States
16	205.372.01069 Boehringer Ingelheim Investigational Site	Miami Beach	Florida	United States
17	205.372.01023 Boehringer Ingelheim Investigational Site	West Palm Beach	Florida	United States
18	205.372.01053 Boehringer Ingelheim Investigational Site	Winter Park	Florida	United States
19	205.372.01045 Boehringer Ingelheim Investigational Site	Calhoun	Georgia	United States
20	205.372.01043 Boehringer Ingelheim Investigational Site	Normal	Illinois	United States
21	205.372.01061 Boehringer Ingelheim Investigational Site	Dubuque	Iowa	United States
22	205.372.01035 Boehringer Ingelheim Investigational Site	Wichita	Kansas	United States
23	205.372.01049 Boehringer Ingelheim Investigational Site	Shreveport	Louisiana	United States
24	205.372.01015 Boehringer Ingelheim Investigational Site	Biddeford	Maine	United States
25	205.372.01067 Boehringer Ingelheim Investigational Site	Columbia	Maryland	United States
26	205.372.01006 Boehringer Ingelheim Investigational Site	Rockville	Maryland	United States
27	205.372.01013 Boehringer Ingelheim Investigational Site	Detroit	Michigan	United States
28	205.372.01003 Boehringer Ingelheim Investigational Site	Minneapolis	Minnesota	United States
29	205.372.01021 Boehringer Ingelheim Investigational Site	Chesterfield	Missouri	United States
30	205.372.01014 Boehringer Ingelheim Investigational Site	St. Louis	Missouri	United States
31	205.372.01036 Boehringer Ingelheim Investigational Site	Omaha	Nebraska	United States
32	205.372.01046 Boehringer Ingelheim Investigational Site	Albuquerque	New Mexico	United States
33	205.372.01024 Boehringer Ingelheim Investigational Site	Mineola	New York	United States
34	205.372.01029 Boehringer Ingelheim Investigational Site	Rochester	New York	United States
35	205.372.01030 Boehringer Ingelheim Investigational Site	Syracuse	New York	United States
36	205.372.01026 Boehringer Ingelheim Investigational Site	Chapel Hill	North Carolina	United States
37	205.372.01019 Boehringer Ingelheim Investigational Site	Charlotte	North Carolina	United States
38	205.372.01027 Boehringer Ingelheim Investigational Site	Elizabeth City	North Carolina	United States
39	205.372.01038 Boehringer Ingelheim Investigational Site	Raleigh	North Carolina	United States
40	205.372.01031 Boehringer Ingelheim Investigational Site	Winston-Salem	North Carolina	United States
41	205.372.01017 Boehringer Ingelheim Investigational Site	Cincinnati	Ohio	United States
42	205.372.01041 Boehringer Ingelheim Investigational Site	Cincinnati	Ohio	United States
43	205.372.01044 Boehringer Ingelheim Investigational Site	Cincinnati	Ohio	United States
44	205.372.01001 Boehringer Ingelheim Investigational Site	Oklahoma City	Oklahoma	United States
45	205.372.01063 Boehringer Ingelheim Investigational Site	Eugene	Oregon	United States
46	205.372.01068 Boehringer Ingelheim Investigational Site	Philadelphia	Pennsylvania	United States
47	205.372.01056 Boehringer Ingelheim Investigational Site	Swathmore	Pennsylvania	United States
48	205.372.01039 Boehringer Ingelheim Investigational Site	Dallas	Texas	United States
49	205.372.01050 Boehringer Ingelheim Investigational Site	Dallas	Texas	United States
50	205.372.01005 Boehringer Ingelheim Investigational Site	Fort Worth	Texas	United States
51	205.372.01018 Boehringer Ingelheim Investigational Site	Killeen	Texas	United States
52	205.372.01040 Boehringer Ingelheim Investigational Site	New Braunfels	Texas	United States
53	205.372.01052 Boehringer Ingelheim Investigational Site	San Antonio	Texas	United States
54	205.372.01022 Boehringer Ingelheim Investigational Site	Danville	Virginia	United States
55	205.372.01065 Boehringer Ingelheim Investigational Site	Lynchburg	Virginia	United States
56	205.372.01055 Boehringer Ingelheim Investigational Site	Richmond	Virginia	United States
57	205.372.01064 Boehringer Ingelheim Investigational Site	Tacoma	Washington	United States
58	205.372.61002 Woolcock Institute of Medical Research	Glebe	New South Wales	Australia
59	205.372.61009 Thoracic & General Physician	Cairns	Queensland	Australia
60	205.372.61005 Redcliffe Hospital	Redcliffe	Queensland	Australia
61	205.372.61006 The Investigator Clinic	Port Lincoln	South Australia	Australia
62	205.372.61007 The Burnside War Memorial Hospital	Toorak Gardens	South Australia	Australia
63	205.372.61004 Boehringer Ingelheim Investigational Site	Woodville	South Australia	Australia
64	205.372.61010 Ecru	Box Hill	Victoria	Australia
65	205.372.61008 Geelong Clinical Research Centre	Geelong	Victoria	Australia
66	205.372.61001 Emeritus Research	Malvern	Victoria	Australia
67	205.372.61003 Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia
68	205.372.55012 Universidade Federal de Santa Catarina	Florianópolis		Brazil
69	205.372.55009 Hospital das Clínicas de Goiânia	Goiânia		Brazil
70	205.372.55005 Hospital Geral Otávio de Freitas	Recife		Brazil
71	205.372.55001 INCOR e Hospital das Clínicas da Universidade de São Paulo	São Paulo - SP		Brazil
72	205.372.55010 Unidade de Coracao e Pulmao do Dto. de Medicina	São Paulo - SP		Brazil
73	205.372.55011 CEDOES - Diagnóstico e Pesquisa	Vitória		Brazil
74	205.372.11007 Heritage Medical Research Building	Calgary	Alberta	Canada
75	205.372.11013 Calgary West Medical Centre	Calgary	Alberta	Canada
76	205.372.11011 Hermitage Medicentre	Edmonton	Alberta	Canada
77	205.372.11017 Boehringer Ingelheim Investigational Site	Edmonton	Alberta	Canada
78	205.372.11020 Wetaskiwin Lung Laboratory	Wetaskiwin	Alberta	Canada
79	205.372.11010 Dr. Kay Ho	Chilliwack	British Columbia	Canada
80	205.372.11018 Pacific Lung Health Centre	Vancouver	British Columbia	Canada
81	205.372.11005 Professional Corp. Respirology	Saint John	New Brunswick	Canada
82	205.372.11009 White Hills Medical Clinic	St. John's	Newfoundland and Labrador	Canada
83	205.372.11012 West Lincoln Memorial Hospital	Grimsby	Ontario	Canada
84	205.372.11014 Dr. Robert Luton	London	Ontario	Canada
85	205.372.11001 Niagara Clinical Research	Niagara Falls	Ontario	Canada
86	205.372.11019 Allergy and Asthma Research Centre	Ottawa	Ontario	Canada
87	205.372.11003 London Road Diagnostic Clinic and Medical Centre	Sarnia	Ontario	Canada
88	205.372.11016 London Road Diagnostic Clinic and Medical Centre	Sarnia	Ontario	Canada
89	205.372.11002 Centenary Respiratory Research Associates	Scarborough	Ontario	Canada
90	205.372.11006 Clinique de médecine familiale de La Malbaie	La Malbaie	Quebec	Canada
91	205.372.11004 Mount Royal Family Physicians	Saskatoon	Saskatchewan	Canada
92	205.372.11015 Dr. Arun Nayar	Saskatoon	Saskatchewan	Canada
93	205.372.86002 Boehringer Ingelheim Investigational Site	Beijing		China
94	205.372.86003 Boehringer Ingelheim Investigational Site	Beijing		China
95	205.372.86004 Boehringer Ingelheim Investigational Site	Beijing		China
96	205.372.86009 Boehringer Ingelheim Investigational Site	Chengdu, Sichuan Province		China
97	205.372.86008 Boehringer Ingelheim Investigational Site	Chongqing		China
98	205.372.86001 Boehringer Ingelheim Investigational Site	Guangzhou		China
99	205.372.86010 Boehringer Ingelheim Investigational Site	Shanghai		China
100	205.372.86011 Boehringer Ingelheim Investigational Site	Shanghai		China
101	205.372.86012 Boehringer Ingelheim Investigational Site	Shanghai		China
102	205.372.86005 Boehringer Ingelheim Investigational Site	Shenyang		China
103	205.372.86006 Boehringer Ingelheim Investigational Site	Shenyang		China
104	205.372.86007 Boehringer Ingelheim Investigational Site	Wuhan		China
105	205.372.45004 Boehringer Ingelheim Investigational Site	Aarhus C		Denmark
106	205.372.45005 Boehringer Ingelheim Investigational Site	Horsens		Denmark
107	205.372.45002 Boehringer Ingelheim Investigational Site	Hvidovre		Denmark
108	205.372.45001 Boehringer Ingelheim Investigational Site	København NV		Denmark
109	205.372.45003 Boehringer Ingelheim Investigational Site	Odense C		Denmark
110	205.372.45006 Boehringer Ingelheim Investigational Site	Silkeborg		Denmark
111	205.372.35804 Boehringer Ingelheim Investigational Site	Helsinki		Finland
112	205.372.35802 Boehringer Ingelheim Investigational Site	Jyväskylä		Finland
113	205.372.35803 Boehringer Ingelheim Investigational Site	Lahti		Finland
114	205.372.35801 Boehringer Ingelheim Investigational Site	Tampere		Finland
115	205.372.3318A Clinique du Parc	Castelnau le Lez		France
116	205.372.3318B Clinique du Parc	Castelnau le Lez		France
117	205.372.3304A Cabinet Médical	Chamalières		France
118	205.372.3301A Hôpital Gabriel Montpied	Clermont Ferrand cedex 1		France
119	205.372.3310A Centre Hospitalier	Denain		France
120	205.372.3314A Cabinet Médical	Grasse		France
121	205.372.3306A Hôpital Ambroise Paré	Marseille		France
122	205.372.3303A Hôpital Notre Dame de Bon Secours	Metz cedex 1		France
123	205.372.3303B Hôpital Notre Dame de Bon Secours	Metz cedex 1		France
124	205.372.3312A Cabinet Médical	Montigny les Metz		France
125	205.372.3312B Cabinet Médical	Montigny les Metz		France
126	205.372.3302A Centre Médical Erdre Saint Augustin	Nantes		France
127	205.372.3305A Cabinet Médical	Nice		France
128	205.372.3305B Cabinet Médical	Nice		France
129	205.372.3315B Hôpital Caremeau	Nimes cedex 9		France
130	205.372.3315A Hôpital Caremeau	Nîmes		France
131	205.372.3317A Cabinet de Pneumologie	Nîmes		France
132	205.372.3320A Polyclinique Les Fleurs	Ollioules		France
133	205.372.3320B Polyclinique Les Fleurs	Ollioules		France
134	205.372.3316A Clinique les Bleuets	Reims		France
135	205.372.3316B Clinique les Bleuets	Reims		France
136	205.372.3319A Institut Arnault Tzanck	Saint Laurent du Var		France
137	205.372.3325A Cabinet Médical	Six Four les Plages		France
138	205.372.3321A Centre Hospitalier	St Gaudens		France
139	205.372.3321C Centre Hospitalier	St Gaudens		France
140	205.372.3324A Cabinet Médical	Toulon		France
141	205.372.3309A Cabinet médical	Toulouse		France
142	205.372.3309B Cabinet médical	Toulouse		France
143	205.372.49002 Boehringer Ingelheim Investigational Site	Berlin		Germany
144	205.372.49004 Boehringer Ingelheim Investigational Site	Berlin		Germany
145	205.372.49013 Boehringer Ingelheim Investigational Site	Berlin		Germany
146	205.372.49007 Boehringer Ingelheim Investigational Site	Bonn		Germany
147	205.372.49008 Boehringer Ingelheim Investigational Site	Bruchsal		Germany
148	205.372.49011 Boehringer Ingelheim Investigational Site	Frankfurt/Main		Germany
149	205.372.49012 Boehringer Ingelheim Investigational Site	Gelnhausen		Germany
150	205.372.49006 Boehringer Ingelheim Investigational Site	Gütersloh		Germany
151	205.372.49014 Boehringer Ingelheim Investigational Site	Hannover		Germany
152	205.372.49005 Boehringer Ingelheim Investigational Site	Kassel		Germany
153	205.372.49009 Boehringer Ingelheim Investigational Site	Minden		Germany
154	205.372.49010 Boehringer Ingelheim Investigational Site	München		Germany
155	205.372.49016 Boehringer Ingelheim Investigational Site	Weinheim		Germany
156	205.372.49015 Boehringer Ingelheim Investigational Site	Weyhe		Germany
157	205.372.49001 Boehringer Ingelheim Investigational Site	Wiesloch		Germany
158	205.372.49003 Boehringer Ingelheim Investigational Site	Witten		Germany
159	205.372.30001 Boehringer Ingelheim Investigational Site	Athens		Greece
160	205.372.30002 Boehringer Ingelheim Investigational Site	Athens		Greece
161	205.372.30003 Boehringer Ingelheim Investigational Site	Athens		Greece
162	205.372.30013 Boehringer Ingelheim Investigational Site	Athens		Greece
163	205.372.30015 Boehringer Ingelheim Investigational Site	Athens		Greece
164	205.372.30009 Boehringer Ingelheim Investigational Site	Heraklion-Crete		Greece
165	205.372.30007 Boehringer Ingelheim Investigational Site	Kalamaria		Greece
166	205.372.30005 Boehringer Ingelheim Investigational Site	Kavala		Greece
167	205.372.30004 Boehringer Ingelheim Investigational Site	Komotini		Greece
168	205.372.30011 Boehringer Ingelheim Investigational Site	Korinthos		Greece
169	205.372.30019 Boehringer Ingelheim Investigational Site	Nafplio		Greece
170	205.372.30008 Boehringer Ingelheim Investigational Site	Serres		Greece
171	205.372.30006 Boehringer Ingelheim Investigational Site	Thessaloniki		Greece
172	205.372.30017 Boehringer Ingelheim Investigational Site	Thessaloniki		Greece
173	205.372.30014 Boehringer Ingelheim Investigational Site	Thiva		Greece
174	205.372.85203 Boehringer Ingelheim Investigational Site	Hong Kong		Hong Kong
175	205.372.85201 Boehringer Ingelheim Investigational Site	Kowloon		Hong Kong
176	205.372.36001 Boehringer Ingelheim Investigational Site	Budapest		Hungary
177	205.372.36002 Boehringer Ingelheim Investigational Site	Debrecen		Hungary
178	205.372.36004 Boehringer Ingelheim Investigational Site	Deszk		Hungary
179	205.372.36005 Boehringer Ingelheim Investigational Site	Erd		Hungary
180	205.372.36006 Boehringer Ingelheim Investigational Site	Mosonmagyarovar		Hungary
181	205.372.36007 Boehringer Ingelheim Investigational Site	Sopron		Hungary
182	205.372.91005 Boehringer Ingelheim Investigational Site	Andhra Pradesh		India
183	205.372.91016 Boehringer Ingelheim Investigational Site	Andhra Pradesh		India
184	205.372.91003 Boehringer Ingelheim Investigational Site	Bangalore		India
185	205.372.91006 Boehringer Ingelheim Investigational Site	Bangalore		India
186	205.372.91017 Boehringer Ingelheim Investigational Site	Calicut,Kerala		India
187	205.372.91007 Boehringer Ingelheim Investigational Site	Chennai		India
188	205.372.91010 Boehringer Ingelheim Investigational Site	Chennai		India
189	205.372.91002 Boehringer Ingelheim Investigational Site	Coimbatore		India
190	205.372.91009 Boehringer Ingelheim Investigational Site	Gujarat		India
191	205.372.91011 Boehringer Ingelheim Investigational Site	indore,MP		India
192	205.372.91012 Boehringer Ingelheim Investigational Site	Maharashtra		India
193	205.372.91004 Boehringer Ingelheim Investigational Site	Mumbai		India
194	205.372.91008 Boehringer Ingelheim Investigational Site	Mumbai		India
195	205.372.91015 Boehringer Ingelheim Investigational Site	New Delhi		India
196	205.372.91014 Boehringer Ingelheim Investigational Site	Punjab		India
197	205.372.91013 Boehringer Ingelheim Investigational Site	Tamil Nadu		India
198	205.372.91001 Boehringer Ingelheim Investigational Site	Uttar Pradesh		India
199	205.372.35303 Boehringer Ingelheim Investigational Site	Mullingar		Ireland
200	205.372.39007 Boehringer Ingelheim Investigational Site	Bussolengo (vr)		Italy
201	205.372.39012 Boehringer Ingelheim Investigational Site	Ferrara		Italy
202	205.372.39003 Boehringer Ingelheim Investigational Site	Genova		Italy
203	205.372.39004 Boehringer Ingelheim Investigational Site	Genova		Italy
204	205.372.39005 Boehringer Ingelheim Investigational Site	Milano		Italy
205	205.372.39008 Boehringer Ingelheim Investigational Site	Modena		Italy
206	205.372.39009 Boehringer Ingelheim Investigational Site	Orbassano (to)		Italy
207	205.372.39001 Boehringer Ingelheim Investigational Site	Pisa		Italy
208	205.372.39010 Boehringer Ingelheim Investigational Site	Pordenone		Italy
209	205.372.39002 Boehringer Ingelheim Investigational Site	Prato (fi)		Italy
210	205.372.39011 Boehringer Ingelheim Investigational Site	Roma		Italy
211	205.372.39006 Boehringer Ingelheim Investigational Site	Trieste		Italy
212	205.372.82010 Boehringer Ingelheim Investigational Site	Anyang		Korea, Republic of
213	205.372.82005 Boehringer Ingelheim Investigational Site	Daegu		Korea, Republic of
214	205.372.82009 Boehringer Ingelheim Investigational Site	Daejoen		Korea, Republic of
215	205.372.82003 Boehringer Ingelheim Investigational Site	Incheon		Korea, Republic of
216	205.372.82008 Boehringer Ingelheim Investigational Site	Jeonbuk		Korea, Republic of
217	205.372.82007 Boehringer Ingelheim Investigational Site	Kwangju		Korea, Republic of
218	205.372.82002 Boehringer Ingelheim Investigational Site	Pusan		Korea, Republic of
219	205.372.82001 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
220	205.372.82004 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
221	205.372.82006 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
222	205.372.37001 Boehringer Ingelheim Investigational Site	Kaunas		Lithuania
223	205.372.37003 Boehringer Ingelheim Investigational Site	Kaunas		Lithuania
224	205.372.37002 Boehringer Ingelheim Investigational Site	Vilnius		Lithuania
225	205.372.60007 Boehringer Ingelheim Investigational Site	Johor Baharu		Malaysia
226	205.372.60004 Boehringer Ingelheim Investigational Site	Kelantan Darul Naim		Malaysia
227	205.372.60005 Boehringer Ingelheim Investigational Site	Kuala Lumpur		Malaysia
228	205.372.60006 Boehringer Ingelheim Investigational Site	Kuala Lumpur		Malaysia
229	205.372.60002 Boehringer Ingelheim Investigational Site	Kuching, Sarawak		Malaysia
230	205.372.60003 Boehringer Ingelheim Investigational Site	Penang		Malaysia
231	205.372.60001 Boehringer Ingelheim Investigational Site	Selangor		Malaysia
232	205.372.52018 Hospital Universitario de Chihuahua	Chihuahua		Mexico
233	205.372.52017 Instituto Nacional de Enfermedades Respiratorias (INER)	Col. Seccion XVI		Mexico
234	205.372.52013 Sanatorio Henri Dunant	Cuernavaca, Mor. México		Mexico
235	205.372.52009 Hospital Civil Antiguo	Guadalajara Jal.		Mexico
236	205.372.52005 Hospital Civil Nuevo de Guadalajara	Guadalajara		Mexico
237	205.372.52001 Hospital General del Estado de Sonora	Hermosillo, Sonora		Mexico
238	205.372.52014 Hospital Angeles de las Lomas	Huixquilucan Edo.Mex.		Mexico
239	205.372.52004 Clínica de Mérida	Merida Yuc.		Mexico
240	205.372.52016 Hospital General de Mexicali	Mexicali Baja California Norte		Mexico
241	205.372.52002 Unidad de Investigación clínica en Medicina	Monterrey, Nuevo León		Mexico
242	205.372.52006 Hospital Universitario	Monterrey, Nuevo León		Mexico
243	205.372.52010 Hospital General Agustin O´Haran	Mérida Yucatán		Mexico
244	205.372.52012 Hospital de Nuestra Señora de la Salud	San Luis Potosi		Mexico
245	205.372.52003 Hospital "Angel Leaño"	Zapopan, Jal.		Mexico
246	205.372.31009 Boehringer Ingelheim Investigational Site	Amsterdam		Netherlands
247	205.372.31006 Boehringer Ingelheim Investigational Site	Drachten		Netherlands
248	205.372.31001 Boehringer Ingelheim Investigational Site	Groningen		Netherlands
249	205.372.31011 Boehringer Ingelheim Investigational Site	Hoofddorp		Netherlands
250	205.372.31007 Boehringer Ingelheim Investigational Site	Leeuwarden		Netherlands
251	205.372.31004 Boehringer Ingelheim Investigational Site	Roosendaal		Netherlands
252	205.372.31003 Boehringer Ingelheim Investigational Site	Sneek		Netherlands
253	205.372.31012 Boehringer Ingelheim Investigational Site	Utrecht		Netherlands
254	205.372.31002 Boehringer Ingelheim Investigational Site	Voorburg		Netherlands
255	205.372.31008 Boehringer Ingelheim Investigational Site	Weerselo		Netherlands
256	205.372.31005 Boehringer Ingelheim Investigational Site	Winschoten		Netherlands
257	205.372.47001 Boehringer Ingelheim Investigational Site	Sandvika		Norway
258	205.372.47003 Boehringer Ingelheim Investigational Site	Trondheim		Norway
259	205.372.47002 Boehringer Ingelheim Investigational Site	Ålesund		Norway
260	205.372.35102 Hospital Fernando Fonseca	Amadora		Portugal
261	205.372.35101 Hospital Pulido Valente	Lisboa		Portugal
262	205.372.35104 Hospital de Santa Marta	Lisboa		Portugal
263	205.372.35103 Hospital de São João	Porto		Portugal
264	205.372.35105 Centro Hospitalar do Alto Minho, Estrada de Santa Luzia	Viana do Castelo		Portugal
265	205.372.65001 Boehringer Ingelheim Investigational Site	Singapore		Singapore
266	205.372.65003 Boehringer Ingelheim Investigational Site	Singapore		Singapore
267	205.372.65005 Boehringer Ingelheim Investigational Site	Singapore		Singapore
268	205.372.42102 Boehringer Ingelheim Investigational Site	Bratislava		Slovakia
269	205.372.42103 Boehringer Ingelheim Investigational Site	Nove Zamky		Slovakia
270	205.372.27002 Boehringer Ingelheim Investigational Site	Bellville		South Africa
271	205.372.27001 Boehringer Ingelheim Investigational Site	Cape Town		South Africa
272	205.372.27004 Boehringer Ingelheim Investigational Site	Cape Town		South Africa
273	205.372.27008 Boehringer Ingelheim Investigational Site	Cape Town		South Africa
274	205.372.27006 Boehringer Ingelheim Investigational Site	Centurion		South Africa
275	205.372.27003 Boehringer Ingelheim Investigational Site	Durban		South Africa
276	205.372.27005 Boehringer Ingelheim Investigational Site	Pretoria		South Africa
277	205.372.27007 Boehringer Ingelheim Investigational Site	Somerset West		South Africa
278	205.372.34005 Hospital San Pedro de Alcántara	Cáceres		Spain
279	205.372.34004 Hospital Gregorio Marañón	Madrid		Spain
280	205.372.34006 Hospital 12 de octubre	Madrid		Spain
281	205.372.34001 Hospital Mutua Terrassa	Terrassa (Barcelona)		Spain
282	205.372.34002 Hospital Universitario Dr. Peset	Valencia		Spain
283	205.372.46001 Björknäs Vårdcentral	Boden		Sweden
284	205.372.46004 Näsets läkargrupp	Höllviken		Sweden
285	205.372.46005 Lungmedicinska kliniken	Linköping		Sweden
286	205.372.46006 Lungmedicinska Kliniken	Stockholm		Sweden
287	205.372.46002 Alnö Vårdcentral	Sundsvall		Sweden
288	205.372.41002 Boehringer Ingelheim Investigational Site	Lugano		Switzerland
289	205.372.41003 Boehringer Ingelheim Investigational Site	Montana		Switzerland
290	205.372.41001 Boehringer Ingelheim Investigational Site	Zürich		Switzerland
291	205.372.88607 Kaohsiung Medical University Hospital	Kaohsiung		Taiwan
292	205.372.88606 National Cheng Kung University Hospital	Tainan		Taiwan
293	205.372.88601 National Taiwan University Hospital	Taipei		Taiwan
294	205.372.88602 Taipei Veterans General Hospital	Taipei		Taiwan
295	205.372.88603 Mackay Memorial Hospital	Taipei		Taiwan
296	205.372.88604 Tri-Service General Hospital	Taipei		Taiwan
297	205.372.88608 Boehringer Ingelheim Investigational Site	Taipei		Taiwan
298	205.372.88609 Boehringer Ingelheim Investigational Site	Taipei		Taiwan
299	205.372.88605 Chang Gung Memorial Hosp-Linkou	Taoyuan		Taiwan
300	205.372.90006 Gazi Universitesi Tip Fakultesi Gogus Hastaliklari A.B.D.	Ankara		Turkey
301	205.372.90007 Atatürk Gög. Hastaliklari ve Cerrahisi Egitim Hastanesi	Ankara		Turkey
302	205.372.90003 Uludag Universitesi Tip Fakultesi Gogus Hastaliklari	Bursa		Turkey
303	205.372.90009 Trakya Universitesi Tip Fakultesi Gogus Hastaliklari A.B.D.	Edirne		Turkey
304	205.372.90004 Dr. Lütfi Kirdar Egitim ve Arastirma Hastanesi	Istanbul		Turkey
305	205.372.90005 Istanbul Universitesi Cerrahpasa Tip Fakultesi	Istanbul		Turkey
306	205.372.90001 Izmir Tepecik Gogus Hastaliklari ve Gogus Cerrahisi Hast.	Izmir		Turkey
307	205.372.90008 Erciyes Universitesi Tip Fakultesi	Kayseri		Turkey
308	205.372.90010 Selcuk Universitesi Tip Fakultesi	Konya		Turkey
309	205.372.90002 19 Mayis Universitesi Tip Fakultesi Gogus Hastaliklari A.B.D	Samsun		Turkey
310	205.372.44027 Boehringer Ingelheim Investigational Site	Aston Clinton, Aylesbury		United Kingdom
311	205.372.44022 Boehringer Ingelheim Investigational Site	Carmarthen		United Kingdom
312	205.372.44002 Boehringer Ingelheim Investigational Site	Chertsey		United Kingdom
313	205.372.44023 Boehringer Ingelheim Investigational Site	Chesterfield		United Kingdom
314	205.372.44014 Boehringer Ingelheim Investigational Site	Darlington		United Kingdom
315	205.372.44009 Boehringer Ingelheim Investigational Site	East Horsley		United Kingdom
316	205.372.44011 Boehringer Ingelheim Investigational Site	Fowey		United Kingdom
317	205.372.44003 Boehringer Ingelheim Investigational Site	Frome		United Kingdom
318	205.372.44026 Boehringer Ingelheim Investigational Site	Greenisland		United Kingdom
319	205.372.44013 Boehringer Ingelheim Investigational Site	Heywood		United Kingdom
320	205.372.44016 Boehringer Ingelheim Investigational Site	Isleworth		United Kingdom
321	205.372.44020 Boehringer Ingelheim Investigational Site	Kirkby in Ashfield		United Kingdom
322	205.372.44024 Boehringer Ingelheim Investigational Site	Mortimer		United Kingdom
323	205.372.44001 Boehringer Ingelheim Investigational Site	Nottingham		United Kingdom
324	205.372.44018 Boehringer Ingelheim Investigational Site	Penzance		United Kingdom
325	205.372.44021 Boehringer Ingelheim Investigational Site	Plymouth		United Kingdom
326	205.372.44007 Boehringer Ingelheim Investigational Site	Sheffield		United Kingdom
327	205.372.44010 Boehringer Ingelheim Investigational Site	Sneinton, Nottingham		United Kingdom
328	205.372.44005 Boehringer Ingelheim Investigational Site	St Just, Penzance		United Kingdom
329	205.372.44015 Boehringer Ingelheim Investigational Site	St. Austell		United Kingdom
330	205.372.44006 Boehringer Ingelheim Investigational Site	Sunderland		United Kingdom
331	205.372.44008 Boehringer Ingelheim Investigational Site	Wellingborough		United Kingdom
332	205.372.44012 Boehringer Ingelheim Investigational Site	Westbury on Trym		United Kingdom
333	205.372.44028 Boehringer Ingelheim Investigational Site	Windsor		United Kingdom
334	205.372.44019 Boehringer Ingelheim Investigational Site	Woking		United Kingdom

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info
• Related Info

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00387088
• Other Study ID Numbers: 205.372; 2006-001009-27
• First Posted: Oct 12, 2006
• Last Update Posted: May 16, 2014
• Last Verified: Sep 1, 2013

• Additional relevant MeSH terms: Pulmonary Disease, Chronic Obstructive; Tiotropium Bromide

Study Results

Participant Flow

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Period Title: Overall Study
STARTED	1989	2002
COMPLETED	1671	1629
NOT COMPLETED	318	373

Baseline Characteristics

Arm/Group Title	Tiotropium	Placebo	Total
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Total of all reporting groups
Overall Participants	1952	1965	3917
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.8 (9.1)	64.8 (9)	64.80 (9.00)
Sex: Female, Male (Count of Participants)
Female	428 21.9%	452 23%	880 22.5%
Male	1524 78.1%	1513 77%	3037 77.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 337
Description	Trough FEV1 is defined as the FEV1 measured at the -10 min time point at the end of the dosing interval (24 h post drug administration).
Time Frame	Baseline and Day 337

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. 133 participants from the FAS were excluded due to insufficient FEV1 data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1889	1870
Least Squares Mean (Standard Error) [Litres]	0.119 (0.007)	0.018 (0.007)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tiotropium, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	ANCOVA with pooled centre, LABA use, and treatment fitted as main effects and the baseline trough FEV1 as a covariate.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.102
	Confidence Interval	(2-Sided) 95%; 0.085 to 0.118
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.009
	Estimation Comments

2. Primary Outcome

Title	Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
Description	Time to first COPD exacerbation (defined as a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment). Time is days from start of study treatment to onset of exacerbation.
Time Frame	During actual study treatment period (planned Day 1 to Day 337)

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1939	1953
Median (95% Confidence Interval) [Days]	NA	NA

3. Secondary Outcome

Title	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29
Description	Trough FEV1 is the mean volume of air that can be forced out in one second after taking a deep breath approximately 24 hours after the last administration of study drug.
Time Frame	Baseline and Day 29

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. 147 participants from the FAS were excluded due to insufficient FEV1 data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1879	1866
Least Squares Mean (Standard Error) [Litres]	0.11 (0.005)	0.017 (0.005)

4. Secondary Outcome

Title	Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 169
Description	Trough FEV1 is the mean volume of air that can be forced out in one second after taking a deep breath approximately 24 hours after the last administration of study drug.
Time Frame	Baseline and Day 169

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. 133 participants from the FAS were excluded due to insufficient FEV1 data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1889	1870
Least Squares Mean (Standard Error) [Litres]	0.121 (0.006)	0.018 (0.006)

5. Secondary Outcome

Title	Number of COPD Exacerbations Per Patient - Exposure Adjusted
Description	Number of COPD exacerbations (defined as a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment) per patient adjusted by length of treatment exposure (i.e. number of exacerbations multiplied by 365.25 and then divided by days of treatment exposure)
Time Frame	During actual study treatment period (planned Day 1 to Day 337)

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1939	1953
Median (Full Range) [COPD exacerbations per year]	0 (0)	0 (0)

6. Secondary Outcome

Title	Number of COPD Exacerbations Per Patient - naïve Estimate
Description	Number of COPD exacerbations (defined as a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment) per patient not adjusted for treatment exposure (i.e. naïve estimate)
Time Frame	During actual study treatment period (planned Day 1 to Day 337)

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1939	1953
Median (Full Range) [COPD exacerbations]	0 (0)	0 (0)

7. Secondary Outcome

Title	Number of Patients With at Least One COPD Exacerbation
Description	Number of patients with at least one COPD exacerbation (defined as a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment)
Time Frame	During actual study treatment period (planned Day 1 to Day 337)

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1939	1953
Number [participants]	685 35.1%	842 42.8%

8. Secondary Outcome

Title	Time to First Hospitalisation for COPD Exacerbation
Description	Time to first hospitalisation for COPD exacerbation (a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment). Time is days from start of study treatment to onset of exacerbation
Time Frame	During actual study treatment period (planned Day 1 to Day 337)

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1939	1953
Median (95% Confidence Interval) [Days]	NA	NA

9. Secondary Outcome

Title	Number of Hospitalisations for COPD Exacerbations Per Patient - Exposure Adjusted
Description	Number of hospitalisations for COPD exacerbations (a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment) per patient adjusted by length of treatment exposure (i.e. no. of exacerbations multiplied by 365.25 and then divided by days of treatment exposure)
Time Frame	During actual study treatment period (planned Day 1 to Day 337)

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1939	1953
Median (Full Range) [hospitalisations for COPD exacerbations]	0 (0)	0 (0)

10. Secondary Outcome

Title	Number of Hospitalisations for COPD Exacerbations Per Patient - naïve Estimate
Description	Number of hospitalisations for COPD exacerbations (a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment) per patient not adjusted for treatment exposure (i.e. naïve estimate)
Time Frame	During actual study treatment period (planned Day 1 to Day 337)

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1939	1953
Median (Full Range) [hospitalisations for COPD exacerbations]	0 (0)	0 (0)

11. Secondary Outcome

Title	Number of Patients With at Least One Hospitalisation for a COPD Exacerbation
Description	Number of patients with at least one hospitalisation for a COPD exacerbation (a complex of respiratory events/symptoms (increase or new onset) with a duration of 3 days or more requiring a change in treatment)
Time Frame	During actual study treatment period (planned Day 1 to Day 337)

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1939	1953
Number [participants]	161 8.2%	198 10.1%

12. Secondary Outcome

Title	Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Day 337
Description	The SGRQ total score measures quality of life on a continuous scale ranging from 0=best state to 100=worst state
Time Frame	Baseline and Day 337

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. 534 participants from the FAS were excluded due to insufficient SGRQ data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1690	1668
Least Squares Mean (Standard Error) [Units on a scale]	-4.726 (0.372)	-1.787 (0.374)

13. Secondary Outcome

Title	Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Day 169
Description	The SGRQ total score measures quality of life on a continuous scale ranging from 0=best state to 100=worst state
Time Frame	Baseline and Day 169

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. 534 participants from the FAS were excluded due to insufficient SGRQ data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1690	1668
Least Squares Mean (Standard Error) [Units on a scale]	-4.764 (0.348)	-2.568 (0.35)

14. Secondary Outcome

Title	Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 337
Description	The SGRQ domain score (symptom, activity and impact) measures quality of life on a continuous scale ranging from 0=best state to 100=worst state
Time Frame	Baseline and Day 337

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. Up to 534 participants from the FAS were excluded due to insufficient SGRQ data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1939	1953
Symptoms (N=1704,1688)	-7.260 (0.546)	-3.307 (0.548)
Activities (N=1690,1668)	-3.196 (0.456)	-0.226 (0.460)
Impacts (N=1690,1668)	-4.873 (0.409)	-2.038 (0.412)

15. Secondary Outcome

Title	Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Domain Score at Day 169
Description	The SGRQ domain score (symptom, activity and impact) measures quality of life on a continuous scale ranging from 0=best state to 100=worst state
Time Frame	Baseline and Day 169

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. Up to 534 participants from the FAS were excluded due to insufficient SGRQ data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1939	1953
Symptoms (N=1704,1688)	-6.555 (0.530)	-3.268 (0.532)
Activities (N=1690,1668)	-3.573 (0.432)	-1.218 (0.435)
Impacts (N=1690,1668)	-4.917 (0.390)	-2.935 (0.392)

16. Secondary Outcome

Title	Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 29
Description	Trough FVC is the mean maximum volume of air that can be forcibly expired from the lungs; measured approximately 24 hours after the last administration of study drug.
Time Frame	Baseline and Day 29

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. 147 participants from the FAS were excluded due to insufficient FVC data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1879	1866
Least Squares Mean (Standard Error) [Litres]	0.176 (0.009)	0.025 (0.009)

17. Secondary Outcome

Title	Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 169
Description	Trough FVC is the mean maximum volume of air that can be forcibly expired from the lungs; measured approximately 24 hours after the last administration of study drug.
Time Frame	Baseline and Day 169

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. 133 participants from the FAS were excluded due to insufficient FVC data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1889	1870
Least Squares Mean (Standard Error) [Litres]	0.179 (0.010)	0.019 (0.010)

18. Secondary Outcome

Title	Change From Baseline in Trough Forced Vital Capacity (FVC) at Day 337
Description	Trough FVC is the mean maximum volume of air that can be forcibly expired from the lungs; measured approximately 24 hours after the last administration of study drug.
Time Frame	Baseline and Day 337

Outcome Measure Data

Analysis Population Description

The FAS was made up of all randomised and treated participants excluding 99 patients with questionable data. 133 participants from the FAS were excluded due to insufficient FVC data.

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1889	1870
Least Squares Mean (Standard Error) [Litres]	0.168 (0.011)	-0.001 (0.011)

19. Secondary Outcome

Title	Marked Changes From Baseline in Vital Signs at End of Treatment
Description	Marked changes from baseline in vital signs (diastolic and systolic blood pressure (DBP and SBP) and pulse rate (PR)) at end of treatment. SBP - Increase means SBP >150 mmHg and an increase above baseline of >25 mmHg. SBP - Decrease means SBP <100 mmHg and a decrease below baseline of >10 mmHg. DBP - Increase means DBP >90 mmHg and an increase above baseline of >10 mmHg. DBP - Decrease means DBP <60 mmHg and a decrease below baseline of >10 mmHg. PR - Increase means PR >100 bpm and an increase above baseline of >10 bpm. PR - Decrease means PR <60 bpm and a decrease below baseline of >10 bpm.
Time Frame	Baseline and end of treatment

Outcome Measure Data

Analysis Population Description

Treated set

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1747	1749
SBP - Increase	29 1.5%	31 1.6%
SBP - Decrease	6 0.3%	12 0.6%
DBP - Increase	40 2%	39 2%
DBP - Decrease	9 0.5%	14 0.7%
PR - Increase	35 1.8%	43 2.2%
PR - Decrease	26 1.3%	26 1.3%

20. Secondary Outcome

Title	Clinically Relevant Findings in Physical Examination and ECG
Description	Clinically relevant findings in Physical Examination and ECG at end of treatment
Time Frame	End of treatment

Outcome Measure Data

Analysis Population Description

Treated set

Arm/Group Title	Tiotropium	Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)	Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
Measure Participants	1952	1965
Phys. Exam - No new/worsened finding	1723 88.3%	1733 88.2%
Phys. Exam - new or worsened finding	22 1.1%	17 0.9%
Phys. Exam - Missing	207 10.6%	215 10.9%
ECG - No new/worsened finding	1674 85.8%	1677 85.3%
ECG - new or worsened finding	37 1.9%	39 2%
ECG - Missing	241 12.3%	249 12.7%

Adverse Events

Time Frame	From first drug administration until 30 days after last drug administration.
Adverse Event Reporting Description	74 patients were excluded from the treated set due to potential fraudulent data from one investigator site
Arm/Group Title	Tiotropium		Placebo
Arm/Group Description	Tiotropium 5µg via Respimat® inhaler (2 inhalations of 2.5µg per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)		Placebo via Respimat® inhaler (2 inhalations per day) + usual maintenance treatment (only anticholinergic bronchodilators were excluded)
All Cause Mortality
	Tiotropium		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Tiotropium		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	342/1952 (17.5%)		336/1965 (17.1%)
Blood and lymphatic system disorders
Anaemia	1/1952 (0.1%)		0/1965 (0%)
Leukocytosis	0/1952 (0%)		1/1965 (0.1%)
Lymphadenopathy mediastinal	0/1952 (0%)		1/1965 (0.1%)
Normochromic normocytic anaemia	1/1952 (0.1%)		0/1965 (0%)
Thrombocytopenia	0/1952 (0%)		1/1965 (0.1%)
Cardiac disorders
Acute coronary syndrome	3/1952 (0.2%)		2/1965 (0.1%)
Acute myocardial infarction	2/1952 (0.1%)		5/1965 (0.3%)
Angina pectoris	4/1952 (0.2%)		3/1965 (0.2%)
Angina unstable	1/1952 (0.1%)		5/1965 (0.3%)
Aortic valve incompetence	1/1952 (0.1%)		0/1965 (0%)
Arrhythmia	2/1952 (0.1%)		1/1965 (0.1%)
Arteriosclerosis coronary artery	0/1952 (0%)		1/1965 (0.1%)
Atrial fibrillation	3/1952 (0.2%)		2/1965 (0.1%)
Atrial flutter	1/1952 (0.1%)		0/1965 (0%)
Atrioventricular block	0/1952 (0%)		2/1965 (0.1%)
Atrioventricular block complete	0/1952 (0%)		1/1965 (0.1%)
Bradyarrhythmia	1/1952 (0.1%)		0/1965 (0%)
Bradycardia	1/1952 (0.1%)		0/1965 (0%)
Cardiac arrest	2/1952 (0.1%)		1/1965 (0.1%)
Cardiac failure	8/1952 (0.4%)		10/1965 (0.5%)
Cardiac failure congestive	5/1952 (0.3%)		4/1965 (0.2%)
Cardiac valve disease	0/1952 (0%)		1/1965 (0.1%)
Cardio-respiratory arrest	4/1952 (0.2%)		1/1965 (0.1%)
Cardiogenic shock	1/1952 (0.1%)		0/1965 (0%)
Cardiomyopathy	1/1952 (0.1%)		0/1965 (0%)
Cardiopulmonary failure	1/1952 (0.1%)		1/1965 (0.1%)
Congestive cardiomyopathy	0/1952 (0%)		1/1965 (0.1%)
Cor pulmonale	2/1952 (0.1%)		3/1965 (0.2%)
Cor pulmonale acute	0/1952 (0%)		1/1965 (0.1%)
Coronary artery disease	5/1952 (0.3%)		2/1965 (0.1%)
Coronary artery occlusion	1/1952 (0.1%)		0/1965 (0%)
Coronary artery stenosis	0/1952 (0%)		1/1965 (0.1%)
Left ventricular failure	2/1952 (0.1%)		1/1965 (0.1%)
Mitral valve incompetence	0/1952 (0%)		2/1965 (0.1%)
Myocardial infarction	5/1952 (0.3%)		5/1965 (0.3%)
Myocardial ischaemia	5/1952 (0.3%)		0/1965 (0%)
Palpitations	1/1952 (0.1%)		0/1965 (0%)
Pericardial effusion	1/1952 (0.1%)		1/1965 (0.1%)
Pericarditis	1/1952 (0.1%)		0/1965 (0%)
Right ventricular failure	1/1952 (0.1%)		1/1965 (0.1%)
Sinus arrhythmia	1/1952 (0.1%)		0/1965 (0%)
Sinus tachycardia	1/1952 (0.1%)		0/1965 (0%)
Supraventricular tachycardia	1/1952 (0.1%)		1/1965 (0.1%)
Tachycardia	1/1952 (0.1%)		1/1965 (0.1%)
Tricuspid valve disease	0/1952 (0%)		1/1965 (0.1%)
Tricuspid valve incompetence	0/1952 (0%)		1/1965 (0.1%)
Ventricular extrasystoles	0/1952 (0%)		1/1965 (0.1%)
Ventricular tachycardia	1/1952 (0.1%)		0/1965 (0%)
Ear and labyrinth disorders
Tinnitus	0/1952 (0%)		1/1965 (0.1%)
Vertigo	1/1952 (0.1%)		1/1965 (0.1%)
Vertigo positional	1/1952 (0.1%)		0/1965 (0%)
Endocrine disorders
Hyperthyroidism	1/1952 (0.1%)		0/1965 (0%)
Eye disorders
Cataract	0/1952 (0%)		1/1965 (0.1%)
Retinal artery occlusion	1/1952 (0.1%)		0/1965 (0%)
Gastrointestinal disorders
Abdominal distension	1/1952 (0.1%)		0/1965 (0%)
Abdominal pain	2/1952 (0.1%)		1/1965 (0.1%)
Abdominal strangulated hernia	1/1952 (0.1%)		0/1965 (0%)
Ascites	1/1952 (0.1%)		0/1965 (0%)
Chilaiditi's syndrome	1/1952 (0.1%)		0/1965 (0%)
Colitis ischaemic	1/1952 (0.1%)		1/1965 (0.1%)
Colonic polyp	1/1952 (0.1%)		0/1965 (0%)
Constipation	2/1952 (0.1%)		0/1965 (0%)
Crohn's disease	0/1952 (0%)		1/1965 (0.1%)
Diarrhoea	0/1952 (0%)		5/1965 (0.3%)
Duodenal ulcer	0/1952 (0%)		2/1965 (0.1%)
Duodenal ulcer haemorrhage	1/1952 (0.1%)		0/1965 (0%)
Dyspepsia	0/1952 (0%)		1/1965 (0.1%)
Dysphagia	1/1952 (0.1%)		0/1965 (0%)
Enterocutaneous fistula	1/1952 (0.1%)		0/1965 (0%)
Erosive oesophagitis	1/1952 (0.1%)		0/1965 (0%)
Food poisoning	0/1952 (0%)		1/1965 (0.1%)
Gastric polyps	1/1952 (0.1%)		0/1965 (0%)
Gastric ulcer haemorrhage	1/1952 (0.1%)		0/1965 (0%)
Gastritis	1/1952 (0.1%)		2/1965 (0.1%)
Gastritis erosive	1/1952 (0.1%)		0/1965 (0%)
Gastritis haemorrhagic	0/1952 (0%)		1/1965 (0.1%)
Gastrooesophageal reflux disease	2/1952 (0.1%)		1/1965 (0.1%)
Haematemesis	1/1952 (0.1%)		0/1965 (0%)
Inguinal hernia	6/1952 (0.3%)		6/1965 (0.3%)
Intestinal ischaemia	1/1952 (0.1%)		0/1965 (0%)
Intestinal obstruction	2/1952 (0.1%)		1/1965 (0.1%)
Intra-abdominal haematoma	0/1952 (0%)		1/1965 (0.1%)
Large intestine perforation	2/1952 (0.1%)		0/1965 (0%)
Melaena	1/1952 (0.1%)		0/1965 (0%)
Nausea	1/1952 (0.1%)		1/1965 (0.1%)
Pancreatitis	1/1952 (0.1%)		0/1965 (0%)
Pancreatitis acute	0/1952 (0%)		1/1965 (0.1%)
Peptic ulcer	1/1952 (0.1%)		0/1965 (0%)
Peptic ulcer haemorrhage	0/1952 (0%)		1/1965 (0.1%)
Proctocolitis	1/1952 (0.1%)		0/1965 (0%)
Rectal haemorrhage	2/1952 (0.1%)		0/1965 (0%)
Reflux oesophagitis	1/1952 (0.1%)		2/1965 (0.1%)
Umbilical hernia	1/1952 (0.1%)		1/1965 (0.1%)
Upper gastrointestinal haemorrhage	0/1952 (0%)		2/1965 (0.1%)
Volvulus	1/1952 (0.1%)		0/1965 (0%)
General disorders
Asthenia	2/1952 (0.1%)		1/1965 (0.1%)
Chest discomfort	2/1952 (0.1%)		0/1965 (0%)
Chest pain	4/1952 (0.2%)		0/1965 (0%)
Death	5/1952 (0.3%)		1/1965 (0.1%)
Drowning	2/1952 (0.1%)		0/1965 (0%)
Drug interaction	1/1952 (0.1%)		0/1965 (0%)
Malaise	0/1952 (0%)		1/1965 (0.1%)
Mass	2/1952 (0.1%)		0/1965 (0%)
Oedema peripheral	2/1952 (0.1%)		1/1965 (0.1%)
Pitting oedema	0/1952 (0%)		1/1965 (0.1%)
Polyp	1/1952 (0.1%)		0/1965 (0%)
Pyrexia	1/1952 (0.1%)		1/1965 (0.1%)
Sudden death	2/1952 (0.1%)		1/1965 (0.1%)
Hepatobiliary disorders
Bile duct stone	0/1952 (0%)		1/1965 (0.1%)
Cholecysititis	1/1952 (0.1%)		1/1965 (0.1%)
Cholecysititis acute	0/1952 (0%)		3/1965 (0.2%)
Cholelithiasis	0/1952 (0%)		2/1965 (0.1%)
Hepatitis acute	0/1952 (0%)		1/1965 (0.1%)
Hyperbilirubinaemia	1/1952 (0.1%)		0/1965 (0%)
Immune system disorders
Anaphylactic reaction	0/1952 (0%)		1/1965 (0.1%)
Infections and infestations
Abscess intestinal	1/1952 (0.1%)		0/1965 (0%)
Acute sinusitis	0/1952 (0%)		1/1965 (0.1%)
Appendicitis	1/1952 (0.1%)		0/1965 (0%)
Bronchitis	7/1952 (0.4%)		6/1965 (0.3%)
Bronchopneumonia	2/1952 (0.1%)		4/1965 (0.2%)
Bronchopulmonary aspergillosis	1/1952 (0.1%)		0/1965 (0%)
Bursitis infective	0/1952 (0%)		1/1965 (0.1%)
Cellulitis	2/1952 (0.1%)		1/1965 (0.1%)
Clostridium difficile colitis	1/1952 (0.1%)		0/1965 (0%)
Cystitis	1/1952 (0.1%)		0/1965 (0%)
Diverticulitis	2/1952 (0.1%)		1/1965 (0.1%)
Empyema	1/1952 (0.1%)		0/1965 (0%)
Endocarditis	1/1952 (0.1%)		0/1965 (0%)
Epiglottitis haemophilus	1/1952 (0.1%)		0/1965 (0%)
Febrile infection	1/1952 (0.1%)		0/1965 (0%)
Gastroenteritis	1/1952 (0.1%)		6/1965 (0.3%)
Gastroenteritis viral	1/1952 (0.1%)		1/1965 (0.1%)
Herpes zoster	0/1952 (0%)		3/1965 (0.2%)
Infection	0/1952 (0%)		2/1965 (0.1%)
Infective exacerbation of chronic obstructive airways disease	9/1952 (0.5%)		18/1965 (0.9%)
Influenza	0/1952 (0%)		2/1965 (0.1%)
Lobar pneumonia	3/1952 (0.2%)		7/1965 (0.4%)
Localised infection	0/1952 (0%)		1/1965 (0.1%)
Lower respiratory tract infection	0/1952 (0%)		6/1965 (0.3%)
Lung infection	0/1952 (0%)		2/1965 (0.1%)
Lung infection pseudomonal	1/1952 (0.1%)		0/1965 (0%)
Osteomyelitis	1/1952 (0.1%)		0/1965 (0%)
Osteomyelitis chronic	0/1952 (0%)		1/1965 (0.1%)
Pharyngeal abscess	1/1952 (0.1%)		0/1965 (0%)
Pneumococcal sepsis	1/1952 (0.1%)		0/1965 (0%)
Pneumonia	26/1952 (1.3%)		37/1965 (1.9%)
Postoperative wound infection	1/1952 (0.1%)		0/1965 (0%)
Pyelonephritis	2/1952 (0.1%)		0/1965 (0%)
Pyelonephritis acute	0/1952 (0%)		1/1965 (0.1%)
Rectal abscess	0/1952 (0%)		1/1965 (0.1%)
Respiratory tract infection	2/1952 (0.1%)		2/1965 (0.1%)
Sepsis	4/1952 (0.2%)		2/1965 (0.1%)
Septic shock	2/1952 (0.1%)		2/1965 (0.1%)
Staphylococcal infection	0/1952 (0%)		1/1965 (0.1%)
Subcutaneous abscess	0/1952 (0%)		1/1965 (0.1%)
Tuberculosis	1/1952 (0.1%)		1/1965 (0.1%)
Upper respiratory tract infection	3/1952 (0.2%)		2/1965 (0.1%)
Urinary tract infection	0/1952 (0%)		1/1965 (0.1%)
Urinary tract infection fungal	1/1952 (0.1%)		0/1965 (0%)
Injury, poisoning and procedural complications
Accident	1/1952 (0.1%)		0/1965 (0%)
Arthropod sting	0/1952 (0%)		1/1965 (0.1%)
Chest injury	1/1952 (0.1%)		0/1965 (0%)
Fall	5/1952 (0.3%)		4/1965 (0.2%)
Femoral neck fracture	1/1952 (0.1%)		2/1965 (0.1%)
Femur fracture	0/1952 (0%)		1/1965 (0.1%)
Head injury	1/1952 (0.1%)		1/1965 (0.1%)
Hip fracture	1/1952 (0.1%)		0/1965 (0%)
Joint dislocation	0/1952 (0%)		1/1965 (0.1%)
Lower limb fracture	0/1952 (0%)		1/1965 (0.1%)
Patella fracture	0/1952 (0%)		1/1965 (0.1%)
Radius fracture	0/1952 (0%)		1/1965 (0.1%)
Rib fracture	3/1952 (0.2%)		1/1965 (0.1%)
Road traffic accident	4/1952 (0.2%)		1/1965 (0.1%)
Spinal compression fracture	0/1952 (0%)		1/1965 (0.1%)
Splenic rupture	1/1952 (0.1%)		0/1965 (0%)
Sternal fracture	1/1952 (0.1%)		0/1965 (0%)
Subdural haematoma	2/1952 (0.1%)		0/1965 (0%)
Tendon injury	0/1952 (0%)		1/1965 (0.1%)
Thermal burn	0/1952 (0%)		1/1965 (0.1%)
Thoracic vertebral fracture	1/1952 (0.1%)		1/1965 (0.1%)
Upper limb fracture	2/1952 (0.1%)		0/1965 (0%)
Investigations
Alanine aminotransferase increased	0/1952 (0%)		1/1965 (0.1%)
Aspartate aminotransferase increased	0/1952 (0%)		1/1965 (0.1%)
Blood alcohol increased	1/1952 (0.1%)		0/1965 (0%)
Blood glucose increased	1/1952 (0.1%)		1/1965 (0.1%)
Blood pressure increased	1/1952 (0.1%)		0/1965 (0%)
Chest x-ray abnormal	1/1952 (0.1%)		0/1965 (0%)
Prostatic specific antigen increased	1/1952 (0.1%)		0/1965 (0%)
Weight decreased	1/1952 (0.1%)		0/1965 (0%)
Metabolism and nutrition disorders
Diabetes mellitus	0/1952 (0%)		1/1965 (0.1%)
Diabetes mellitus inadequate control	2/1952 (0.1%)		0/1965 (0%)
Diabetic foot	2/1952 (0.1%)		0/1965 (0%)
Electrolyte imbalance	0/1952 (0%)		1/1965 (0.1%)
Gout	1/1952 (0.1%)		0/1965 (0%)
Hypercalcaemia	0/1952 (0%)		1/1965 (0.1%)
Hypoglycaemia	1/1952 (0.1%)		1/1965 (0.1%)
Hypokalaemia	2/1952 (0.1%)		2/1965 (0.1%)
Hypomagnesaemia	0/1952 (0%)		1/1965 (0.1%)
Hyponatraemia	0/1952 (0%)		2/1965 (0.1%)
Musculoskeletal and connective tissue disorders
Back pain	2/1952 (0.1%)		2/1965 (0.1%)
Bursitis	0/1952 (0%)		1/1965 (0.1%)
Cervical spinal stenosis	0/1952 (0%)		1/1965 (0.1%)
Facet joint syndrome	0/1952 (0%)		1/1965 (0.1%)
Intervertebral disc protrusion	1/1952 (0.1%)		0/1965 (0%)
Joint swelling	1/1952 (0.1%)		0/1965 (0%)
Lumbar spinal stenosis	1/1952 (0.1%)		0/1965 (0%)
Muscular weakness	1/1952 (0.1%)		0/1965 (0%)
Musculoskeletal chest pain	0/1952 (0%)		2/1965 (0.1%)
Myalgia	0/1952 (0%)		1/1965 (0.1%)
Osteoarthritis	1/1952 (0.1%)		0/1965 (0%)
Osteoporotic fracture	1/1952 (0.1%)		0/1965 (0%)
Pain in extremity	0/1952 (0%)		1/1965 (0.1%)
Rotator cuff syndrome	1/1952 (0.1%)		1/1965 (0.1%)
Spinal osteoarthritis	1/1952 (0.1%)		0/1965 (0%)
Tenosynovitis	0/1952 (0%)		1/1965 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myelomonocytic leukaemia	1/1952 (0.1%)		0/1965 (0%)
Basal cell carcinoma	1/1952 (0.1%)		1/1965 (0.1%)
Benigh neoplasm of bladder	1/1952 (0.1%)		0/1965 (0%)
Benign neoplasm of thyroid gland	0/1952 (0%)		1/1965 (0.1%)
Bladder cancer	1/1952 (0.1%)		2/1965 (0.1%)
Bladder neoplasm	2/1952 (0.1%)		1/1965 (0.1%)
Bladder transitional cell carcinoma	1/1952 (0.1%)		0/1965 (0%)
Bone cancer metastatic	0/1952 (0%)		1/1965 (0.1%)
Brain cancer metastatic	0/1952 (0%)		1/1965 (0.1%)
Brain neoplasm	3/1952 (0.2%)		0/1965 (0%)
Breast cancer	1/1952 (0.1%)		1/1965 (0.1%)
Bronchial carcinoma	3/1952 (0.2%)		2/1965 (0.1%)
Colon adenoma	1/1952 (0.1%)		0/1965 (0%)
Colon cancer	2/1952 (0.1%)		1/1965 (0.1%)
Gastric cancer	3/1952 (0.2%)		1/1965 (0.1%)
Gastrointestinal carcinoma	0/1952 (0%)		1/1965 (0.1%)
Hepatic cancer metastatic	0/1952 (0%)		1/1965 (0.1%)
Hepatic neoplasm malignant	1/1952 (0.1%)		3/1965 (0.2%)
Hypopharyngeal neoplasm	0/1952 (0%)		1/1965 (0.1%)
Keratoacanthoma	1/1952 (0.1%)		0/1965 (0%)
Lung adenocarcinoma	0/1952 (0%)		1/1965 (0.1%)
Lung neoplasm	1/1952 (0.1%)		1/1965 (0.1%)
Lung neoplasm malignant	10/1952 (0.5%)		2/1965 (0.1%)
Lung squamous cell carcinoma stage unspecified	1/1952 (0.1%)		0/1965 (0%)
Meningioma	1/1952 (0.1%)		0/1965 (0%)
Metastases to bone	0/1952 (0%)		1/1965 (0.1%)
Metastases to liver	1/1952 (0.1%)		0/1965 (0%)
Metastases to lung	1/1952 (0.1%)		0/1965 (0%)
Metastases to skin	1/1952 (0.1%)		0/1965 (0%)
Metastases to spine	1/1952 (0.1%)		0/1965 (0%)
Multiple myeloma	1/1952 (0.1%)		0/1965 (0%)
Neoplasm	0/1952 (0%)		1/1965 (0.1%)
Neoplasm prostate	1/1952 (0.1%)		0/1965 (0%)
Non-small cell lung cancer	1/1952 (0.1%)		0/1965 (0%)
Non-small cell lung cancer metastatic	0/1952 (0%)		1/1965 (0.1%)
Prostate cancer	2/1952 (0.1%)		1/1965 (0.1%)
Renal cancer	0/1952 (0%)		1/1965 (0.1%)
Renal neoplasm	1/1952 (0.1%)		0/1965 (0%)
Squamous cell carcinoma	2/1952 (0.1%)		0/1965 (0%)
Nervous system disorders
Ataxia	0/1952 (0%)		1/1965 (0.1%)
Carotid artery stenosis	0/1952 (0%)		2/1965 (0.1%)
Carpal tunnel syndrome	1/1952 (0.1%)		0/1965 (0%)
Cerebral circulatory failure	0/1952 (0%)		1/1965 (0.1%)
Cerebral haemorrhage	1/1952 (0.1%)		0/1965 (0%)
Cerebral infarction	3/1952 (0.2%)		2/1965 (0.1%)
Cerebral thrombosis	1/1952 (0.1%)		0/1965 (0%)
Cerebrovascular accident	0/1952 (0%)		2/1965 (0.1%)
Cerebrovascular disorder	0/1952 (0%)		1/1965 (0.1%)
Cervical myelopathy	0/1952 (0%)		1/1965 (0.1%)
Convulsion	1/1952 (0.1%)		0/1965 (0%)
Dementia	0/1952 (0%)		1/1965 (0.1%)
Dizziness	1/1952 (0.1%)		2/1965 (0.1%)
Dysarthria	1/1952 (0.1%)		0/1965 (0%)
Hemiplegia	1/1952 (0.1%)		0/1965 (0%)
Ischaemic stroke	2/1952 (0.1%)		1/1965 (0.1%)
Lethargy	0/1952 (0%)		1/1965 (0.1%)
Loss of consciousness	1/1952 (0.1%)		1/1965 (0.1%)
Monoparesis	0/1952 (0%)		1/1965 (0.1%)
Presyncope	1/1952 (0.1%)		0/1965 (0%)
Sciatica	0/1952 (0%)		1/1965 (0.1%)
Somnolence	0/1952 (0%)		1/1965 (0.1%)
Syncope	2/1952 (0.1%)		0/1965 (0%)
Syncope vasovagal	1/1952 (0.1%)		0/1965 (0%)
Transient ischaemic attack	2/1952 (0.1%)		3/1965 (0.2%)
Unresponsive to stimuli	1/1952 (0.1%)		0/1965 (0%)
Vascular dementia	0/1952 (0%)		1/1965 (0.1%)
Haemorrhagic cerebral infarction	0/1952 (0%)		1/1965 (0.1%)
Psychiatric disorders
Completed suicide	0/1952 (0%)		1/1965 (0.1%)
Confusional state	1/1952 (0.1%)		2/1965 (0.1%)
Delirium	0/1952 (0%)		1/1965 (0.1%)
Depression	0/1952 (0%)		1/1965 (0.1%)
Mental status changes	0/1952 (0%)		1/1965 (0.1%)
Psychotic disorder	0/1952 (0%)		1/1965 (0.1%)
Stress	1/1952 (0.1%)		0/1965 (0%)
Suicide attempt	1/1952 (0.1%)		0/1965 (0%)
Renal and urinary disorders
Calculus ureteric	2/1952 (0.1%)		1/1965 (0.1%)
Dysuria	1/1952 (0.1%)		0/1965 (0%)
Haematuria	2/1952 (0.1%)		0/1965 (0%)
Hydronephrosis	0/1952 (0%)		1/1965 (0.1%)
Incontinence	0/1952 (0%)		1/1965 (0.1%)
Nephrolithiasis	1/1952 (0.1%)		0/1965 (0%)
Nephrotic syndrome	1/1952 (0.1%)		0/1965 (0%)
Renal failure	3/1952 (0.2%)		1/1965 (0.1%)
Renal failure acute	3/1952 (0.2%)		2/1965 (0.1%)
Urethral meatus stenosis	0/1952 (0%)		1/1965 (0.1%)
Urinary retention	5/1952 (0.3%)		1/1965 (0.1%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	6/1952 (0.3%)		3/1965 (0.2%)
Prostatic haemorrhage	1/1952 (0.1%)		0/1965 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/1952 (0%)		1/1965 (0.1%)
Acute respiratory failure	4/1952 (0.2%)		3/1965 (0.2%)
Asphyxia	1/1952 (0.1%)		0/1965 (0%)
Atelectasis	1/1952 (0.1%)		0/1965 (0%)
Chronic obstructive pulmonary disease	130/1952 (6.7%)		155/1965 (7.9%)
Cough	2/1952 (0.1%)		1/1965 (0.1%)
Dyspnoea	10/1952 (0.5%)		4/1965 (0.2%)
Dyspnoea exertional	1/1952 (0.1%)		0/1965 (0%)
Emphysema	2/1952 (0.1%)		1/1965 (0.1%)
Epistaxis	1/1952 (0.1%)		1/1965 (0.1%)
Haemoptysis	3/1952 (0.2%)		3/1965 (0.2%)
Haemothorax	1/1952 (0.1%)		0/1965 (0%)
Hypoxia	2/1952 (0.1%)		1/1965 (0.1%)
Lung disorder	1/1952 (0.1%)		1/1965 (0.1%)
Lung infiltration	0/1952 (0%)		1/1965 (0.1%)
Pleural effusion	2/1952 (0.1%)		2/1965 (0.1%)
Pneumonia aspiration	2/1952 (0.1%)		0/1965 (0%)
Pneumothorax	6/1952 (0.3%)		7/1965 (0.4%)
Pulmonary embolism	3/1952 (0.2%)		2/1965 (0.1%)
Pulmonary fistula	0/1952 (0%)		1/1965 (0.1%)
Pulmonary hypertension	1/1952 (0.1%)		0/1965 (0%)
Pulmonary mass	0/1952 (0%)		1/1965 (0.1%)
Pulmonary oedema	3/1952 (0.2%)		1/1965 (0.1%)
Respiratory acidosis	0/1952 (0%)		1/1965 (0.1%)
Respiratory arrest	2/1952 (0.1%)		0/1965 (0%)
Respiratory disorder	0/1952 (0%)		1/1965 (0.1%)
Respiratory failure	9/1952 (0.5%)		11/1965 (0.6%)
Tachypnoea	0/1952 (0%)		1/1965 (0.1%)
Skin and subcutaneous tissue disorders
Lichen nitidus	1/1952 (0.1%)		0/1965 (0%)
Pruritus	1/1952 (0.1%)		0/1965 (0%)
Rash	0/1952 (0%)		1/1965 (0.1%)
Social circumstances
Living in residential institution	1/1952 (0.1%)		0/1965 (0%)
Surgical and medical procedures
Gallbladder operation	1/1952 (0.1%)		0/1965 (0%)
Hysterectomy	0/1952 (0%)		1/1965 (0.1%)
Ileostomy closure	1/1952 (0.1%)		0/1965 (0%)
Shoulder arthroplasty	0/1952 (0%)		1/1965 (0.1%)
Urethrotomy	1/1952 (0.1%)		0/1965 (0%)
Vascular disorders
Aortic aneurysm	2/1952 (0.1%)		2/1965 (0.1%)
Aortic rupture	0/1952 (0%)		1/1965 (0.1%)
Aortic stenosis	0/1952 (0%)		1/1965 (0.1%)
Arterial stenosis	1/1952 (0.1%)		0/1965 (0%)
Arteriosclerosis	0/1952 (0%)		1/1965 (0.1%)
Deep vein thrombosis	0/1952 (0%)		1/1965 (0.1%)
Haemorrhage	0/1952 (0%)		1/1965 (0.1%)
Hypertension	1/1952 (0.1%)		0/1965 (0%)
Hypertensive crisis	1/1952 (0.1%)		0/1965 (0%)
Hypotension	2/1952 (0.1%)		2/1965 (0.1%)
Hypovolaemic shock	0/1952 (0%)		1/1965 (0.1%)
Intermittent claudication	1/1952 (0.1%)		0/1965 (0%)
Phlebitis	0/1952 (0%)		1/1965 (0.1%)
Venous insufficiency	0/1952 (0%)		1/1965 (0.1%)
Other (Not Including Serious) Adverse Events
	Tiotropium		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	866/1952 (44.4%)		926/1965 (47.1%)
Infections and infestations
Nasopharyngitis	157/1952 (8%)		151/1965 (7.7%)
Upper respiratory tract infection	97/1952 (5%)		123/1965 (6.3%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	561/1952 (28.7%)		659/1965 (33.5%)
Dyspnoea	122/1952 (6.3%)		144/1965 (7.3%)
Cough	123/1952 (6.3%)		106/1965 (5.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.