Clinical trial NCT00274573: Effects of Once Daily Tiotropium in Patients With Chronic Obstructive Pulmonary Disease (COPD) of Different Severity
Official title: Acute and Long-term Effects of Once Daily Oral Inhalation of Tiotropium 18 Mcg Dry Powder Inhalation Capsules in a Placebo Controlled Parallel Group Design Study in Patients With Chronic Obstructive Pulmonary Disease (COPD) of Different Severity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2006-01-11
Enrollment: 1639
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to investigate the effect of tiotropium vs. placebo on trough FEV1 and FEV1 2 hours post inhalation after 12 weeks of treatment. For both endpoints changes from baseline will be analysed. Three strata of patients will be included (severe COPD, i.e. \<35% of predicted FEV1, moderate COPD, i.e. 35% - \<50% of predicted FEV1, mild COPD, i.e. 50% - 70% of predicted FEV1, according to American Thoracic Society \[ATS\] criteria). The study is conducted in order to find out for which endpoint tiotropium is different from placebo in which stratum.


Eligibility criteria: Inclusion Criteria:

1. All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:

   * Patients must have relatively stable, mild to severe airway obstruction with an FEV1 =\<70% of predicted normal and an FEV1/FVC \< 70 %.
   * Predicted normal values will be taken from the print-outs of the spirometers. Spirometers have to calibrated according to ECCS.
2. Male or female patients 40 years of age or older.
3. Patients must be current or ex-smokers with a smoking history of 10 or more than 10 pack-years. Pack Years = Number of cigarettes/day : 20 x years of smoking (Patients who have never smoked cigarettes must not be included)
4. Patients must be able to perform all study related tests, acceptable pulmonary function tests, including Peak Expiratory Flow Rate (PEFR) measurements, and must be able to maintain diary cards during the study period as required in the protocol.
5. Patients must be able to inhale medication from the HandiHaler.
6. All patients must sign an Informed Consent Form prior to participation in the trial i.e. prior to pre-study washout of their usual pulmonary medications.

Exclusion Criteria:

1. Patients with significant diseases other than COPD will be excluded. A significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study.
2. Patients with a recent history (i.e., one year or less) of myocardial infarction.
3. Patients with any cardiac arrhythmia requiring drug therapy or who have been hospitalised for heart failure within the past three years.
4. Patients who regularly use daytime oxygen therapy for more than 1 hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy.
5. Patients with known active tuberculosis.
6. Patients with a history of cancer within the last five years. Patients with treated basal cell carcinoma are allowed.
7. Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis.
8. Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion 1.
9. Patients with any respiratory infection in the past six weeks prior to the Screening Visit (Visit 1) or during the run-in period.
10. Patients who are currently in a pulmonary rehabilitation programme or who have completed a pulmonary rehabilitation programme in the six week prior to the Screening Visit (Visit 1).
11. Patients with known hypersensitivity to anticholinergic drugs, lactose or any other components of the inhalation capsule delivery system.
12. Patients with known symptomatic prostate hypertrophy or bladder neck obstruction.
13. Patients with known narrow-angle glaucoma.
14. Patients using oral corticosteroid medication at unstable doses (i.e., less than four weeks on a stable dose before Visit 1) or at doses in excess of the equivalent of 10 mg of prednisolone per day or 20 mg every other day.
15. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e. oral contraceptives, intrauterine devices, diaphragm or subdermal implants).
16. Patients with a history of asthma, allergic rhinitis or atopy.
17. Patients with a history of and/or active significant alcohol or drug abuse.
18. Patients who have taken an investigational drug within one month prior to Screening Visit (Visit 1). A log of all subjects screened, and reasons for exclusion for those not randomised will be maintained.

Primary outcomes:
measure: Change from baseline in trough FEV1 (Forced expiratory volume in one second)
timeFrame: after 12 weeks
measure: Change from baseline in FEV1 2 hours post inhalation
timeFrame: after 12 weeks
Secondary outcomes:
measure: Change from baseline in FEV1 2 hours post inhalation
timeFrame: Day 1
measure: Change from baseline in FVC (Forced Vital Capacity) 2 hours post inhalation
timeFrame: Day 1 and 85
measure: Change from baseline in IVC (Inspiratory Vital Capacity) 2 hours post inhalation
timeFrame: Day 1 and 85
measure: Number of patients having a COPD exacerbation
timeFrame: 12 weeks
measure: Number of patients being hospitalised due to a COPD exacerbation
timeFrame: 12 weeks
measure: Number of COPD exacerbations per patient
timeFrame: 12 weeks
measure: Number hospitalisations due to COPD exacerbations per patient
timeFrame: 12 weeks
measure: Duration of COPD exacerbations per patient
timeFrame: 12 weeks
measure: Duration of hospitalisations due to a COPD exacerbation
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Ahrensburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Altenburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Amberg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Aschaffenburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Auerbach
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Aue
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Augsburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Backnang
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Bad Kissingen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Bad Krozingen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Bad Lippspringe
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Bad Nauheim
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Bad Neustadt
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Bad Soden
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Baunatal
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Beckum
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Bensheim
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: MEDARS GmbH
city: Bernau
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Bielefeld
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Bochum
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Bonn
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Brake
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Brandenburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Braunschweig
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Bruchsal
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Buchholz
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Celle
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Chemnitz
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Cloppenburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Coburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Dachau
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Darmstadt
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Deggendorf
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Delmenhorst
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Detmold
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Dillingen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Dinslaken
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Dortmund
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Dresden
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Duisburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Dülmen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Düren
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Düsseldorf
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Eggenfelden
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Eisenach
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Eisenhüttenstadt
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Emden
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Erfurt
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Erlangen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Essen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Euskirchen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Fellbach
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Fluda
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Frankenthal
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Frankfurt/Main
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Frankfurt/Oder
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Freising
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Fulda
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Fürstenfeldbruck
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Fürstenwalde
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Fürth
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Garmisch-Partenkirchen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Gelsenkirchen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Germering
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Goch
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Greiz
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Groß Gaglow
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Großenhain
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Göppingen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Gütersloh
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Hagen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Hamm
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Hannover
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Hartha
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Heidelberg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Heidenheim
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Heilbronn
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Hemmingen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Hildburghausen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Hildesheim
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Homburg/Saar
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Hoyerswerda
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Ingolstadt
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Kamen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Karlsruhe
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Kaufbeuren
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Kempten
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Kiel
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Koblenz
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Krefeld
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Köln
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Köthen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Landshut
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Langenhagen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Leipzig
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Leonberg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Ludwigsburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Lörrach
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Lübeck
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Lüdenscheid
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Lüneburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Magdeburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: Johannes-Gutenberg-Universität Mainz
city: Mannheim
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Marburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Markkleeberg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Minden
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Mittweida
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Moers
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Mönchengladbach
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Mühlhausen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Münster
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Neu-Isenburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Neu-Ulm
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Neubrandenburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Neuss
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Neuwied
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Niesky
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Nordhausen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Nortorf
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Oschatz
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Oschersleben
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Papenburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Potsdam
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Rathenow
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Recklinghausen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Regensburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Rehau
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Remscheid
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Reutlingen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Rhaunen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Rostock
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Rüdersdorf
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Rüsselsheim
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Saarbrücken
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Saarlouis
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Schrobenhausen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Schwabach
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Schweinfurt
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Schwetzingen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Schwäbisch Gmünd
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Siegen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Simmern
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Sindelfingen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Singen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Solingen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Sonneberg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: St. Ingbert
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Stade
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Steinhagen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Stolberg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Stuttgart
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Teuchern
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Ulm
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Uttenreuth
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Vechta
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Velbert
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Verden
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Vöhringen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Waiblingen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Waren
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Welzheim
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Weyhe
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Wiesbaden
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Wiesloch
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Witten
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Wolfsburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Wuppertal
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Zerbst
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Zwickau
country: Germany
facility: Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim KG
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References: