Effect of Tiotropium Plus Salmeterol vs. Fluticasone/Salmeterol on Static Lung Volumes and Exercise Endurance in COPD
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Registration Number
- NCT00530842
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The primary objective of this study is to demonstrate that treatment with a free combination of tiotropium and salmeterol provides superior improvement in static lung volumes and exercise tolerance compared to a fixed combination of fluticasone and salmeterol in patients with COPD.
The secondary objective includes assessment of safety.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 344
-
The patient has signed an Informed Consent Form in accordance with GCP and local legislative requirements prior to participation in the trial, i.e., prior to pre-trial washout of any restricted medications.
-
The patient has a clinical diagnosis of chronic obstructive pulmonary disease (COPD).
-
The patient has relatively stable, moderate to severe airway obstruction.
-
The patient has a pre-bronchodilator forced expiratory volume in the first second (FEV1) less than or equal to 65% of predicted normal determined at Visit 1 using the following predicted equations (R94-1408):
- Males Forced expiratory volume in the first second (FEV1) predicted [Litres (L)] = 4.30 x Height [metres] minus 0.029 x Age [years] minus 2.49
- Females Forced expiratory volume in the first second (FEV1) predicted [Litres (L)] = 3.95 x Height [metres] minus 0.025 x Age [years] minus 2.60 and a Thoracic Gas Volume (Functional residual volume) ((TGV)(FRC)) bigger than 120% predicted normal at visit 1 (or historical data not older than 6 month)
- Males Thoracic Gas Volume (Functional residual volume) ((TGV(FRC)) pred. [Litres (L)] = 2.34 x Height [metres] + 0.009 x Age [years] minus 1.09
- Females Thoracic Gas Volume (Functional residual volume) ((TGV(FRC)) pred. [Litres (L)] = 2.24 x Height [metres] + 0.001 x Age [years] minus 1.00
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The patient is at least 40 years and less than or equal to 75 years old.
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The patient has a cigarette smoking history of at least 10 pack-years. A pack-year is defined as the equivalent of smoking one pack of cigarettes per day for a year.
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The patient is able to perform all specified procedures and able to maintain all necessary records during the study period as required in the protocol.
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The patient is able to inhale the trial medication from the HandiHaler device.
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The patient is able to inhale the trial medication from the Diskus/Accuhaler device.
- a significant disease other than chronic obstructive pulmonary disease (COPD). (review contraindications for exercise testing),
- a recent history of myocardial infarction within one year.
- a recent history of heart failure, pulmonary oedema, or patients with cardiac arrhythmia or any contraindication to exercise described in the CTProtocol within the last 3.
- daytime supplemental oxygen.
- a diagnosis of known active tuberculosis.
- a history of cancer within the last 5 years.
- a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis.
- thoracotomy with pulmonary resection.
- an upper respiratory tract infection or an exacerbation of chronic obstructive pulmonary disease (COPD)
- a known hypersensitivity to anticholinergic drug, ß-adrenergic or corticosteroids, lactose or any other component of the inhalation capsule delivery system.
- a known symptomatic prostatic hypertrophy or bladder neck obstruction.
- a known moderate or severe renal insufficiency.
- a known narrow-angle glaucoma.
- a known untreated hypokalemia.
- a known untreated thyrotoxicosis.
- a history of asthma, allergic rhinitis or atopy, or a total blood eosinophil count larger than 600/mm3.
- treatment with cromolyn sodium or nedocromil sodium
- treatment with antihistamines or antileukotrienes.
- treatment with tiotropium for 1 month before Visit 1.
- treatment with oral corticosteroid medication.
- Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception
- a history of or active alcohol or drug abuse.
- an investigational drug within 1 month or 10 half lives
- a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea.
- participation in a rehabilitation program for chronic obstructive pulmonary disease (COPD).
- treatment with monoamine oxidase inhibitors inhibitors or tricyclic antidepressants.
- participation in another study.
- more than eight puffs of salbutamol/day during the run-in period
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Primary Outcome Measures
Name Time Method Post-dose TGV(FRC) (After 8 Weeks) 8 weeks Post-dose TGV(FRC) (Thoracic Gas Volume; co-primary endpoint) after 8 weeks
Endurance Time (After 8 Weeks) 8 weeks Endurance time to the point of symptom limitation after 8 weeks during a constant work rate exercise test at 75% Wcap (co-primary endpoint)
- Secondary Outcome Measures
Name Time Method Static Lung Volumes 4 weeks Post-dose TLC (Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)
FEV1 Over FVC (Percent) 4 weeks Post-dose FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)
Symptom Intensity During Exercise 4 weeks Isotime Borg leg discomfort scale after 4 weeks, Unit on a Scale (min. 0, max. 10), 0 = no leg dyscomfort, 10 = worst imaginable leg dyscomfort
Forced Expiratory Volume in 1 Second (FEV1) 4 weeks Post-dose percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 4 weeks (measured by spirometry)
Locus of Symptom Limitation at Peak Exercise During Exercise 8 weeks Reason for stopping exercise after 8 weeks (leg discomfort, breathing discomfort, both or none)
Post-dose TGV(FRC) (After 4 Weeks) 4 weeks Post-dose TGV(FRC) (Thoracic Gas Volume) after 4 weeks
Endurance Time (After 4 Weeks) 4 weeks Endurance time to the point of symptom limitation after 4 weeks during a constant work rate exercise test at 75% Wcap (co-primary endpoint)
Dyspnea and Leg Discomfort 8 weeks Peak Borg leg discomfort scale after 8 weeks, Unit on a Scale (min. 0, max 10)
Static Lung Volumes (Percent) 4 weeks Post-dose TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)
Slow Vital Capacity (SVC) 4 weeks Post-dose SVC (Slow Vital Capacity) after 4 weeks (measured by spirometry)
Forced Vital Capacity (FVC) 4 weeks Post-dose FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)
Trial Locations
- Locations (42)
205.334.4309 Boehringer Ingelheim Investigational Site
🇦🇹Gänserndorf, Austria
205.334.4904 Boehringer Ingelheim Investigational Site
🇩🇪Donaustauf, Germany
205.334.4901 Boehringer Ingelheim Investigational Site
🇩🇪Großhansdorf, Germany
205.334.3304A Boehringer Ingelheim Investigational Site
🇫🇷St Priest en Jarez, France
205.334.3306B Boehringer Ingelheim Investigational Site
🇫🇷Strasbourg, France
205.334.4308 Boehringer Ingelheim Investigational Site
🇦🇹Hallein, Austria
205.334.1005 Boehringer Ingelheim Investigational Site
🇨🇦Hamilton, Ontario, Canada
205.334.3301A Boehringer Ingelheim Investigational Site
🇫🇷Grenoble, France
205.334.1006 Boehringer Ingelheim Investigational Site
🇨🇦Quebec, Canada
205.334.3303B Boehringer Ingelheim Investigational Site
🇫🇷Beuvry, France
205.334.1004 Boehringer Ingelheim Investigational Site
🇨🇦Ottawa, Ontario, Canada
205.334.3303A Boehringer Ingelheim Investigational Site
🇫🇷Beuvry, France
205.334.3305A Boehringer Ingelheim Investigational Site
🇫🇷Créteil, France
205.334.3302A Boehringer Ingelheim Investigational Site
🇫🇷Toulouse, France
205.334.3302B Boehringer Ingelheim Investigational Site
🇫🇷Toulouse, France
205.334.4908 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
205.334.4909 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
205.334.4907 Boehringer Ingelheim Investigational Site
🇩🇪Kiel, Germany
205.334.39007 Boehringer Ingelheim Investigational Site
🇮🇹Catania, Italy
205.334.4902 Boehringer Ingelheim Investigational Site
🇩🇪Köln, Germany
205.334.39002 Boehringer Ingelheim Investigational Site
🇮🇹Gaiato Pavullo (mo), Italy
205.334.39004 Boehringer Ingelheim Investigational Site
🇮🇹Milano, Italy
205.334.46003 Boehringer Ingelheim Investigational Site
🇸🇪Jönköping, Sweden
205.334.46002 Boehringer Ingelheim Investigational Site
🇸🇪Lund, Sweden
205.334.46001 Boehringer Ingelheim Investigational Site
🇸🇪Uppsala, Sweden
205.334.4306 Boehringer Ingelheim Investigational Site
🇦🇹Leoben, Austria
205.334.4301 Boehringer Ingelheim Investigational Site
🇦🇹Linz, Austria
205.334.4302 Boehringer Ingelheim Investigational Site
🇦🇹Neumarkt am Wallersee, Austria
205.334.4305 Boehringer Ingelheim Investigational Site
🇦🇹Salzburg, Austria
205.334.1009 Boehringer Ingelheim Investigational Site
🇨🇦Vancouver, British Columbia, Canada
205.334.1003 Boehringer Ingelheim Investigational Site
🇨🇦Halifax, Nova Scotia, Canada
205.334.7001 Boehringer Ingelheim Investigational Site
🇷🇺Moscow, Russian Federation
205.334.1007 Boehringer Ingelheim Investigational Site
🇨🇦Saskatoon, Saskatchewan, Canada
205.334.1001 Boehringer Ingelheim Investigational Site
🇨🇦Montreal, Quebec, Canada
205.334.7002 Boehringer Ingelheim Investigational Site
🇷🇺Moscow, Russian Federation
205.334.7003 Boehringer Ingelheim Investigational Site
🇷🇺St. Petersburg, Russian Federation
205.334.39001 Boehringer Ingelheim Investigational Site
🇮🇹Pisa, Italy
205.334.39005 Boehringer Ingelheim Investigational Site
🇮🇹Roma, Italy
205.334.39006 Boehringer Ingelheim Investigational Site
🇮🇹Roma, Italy
205.334.3306A Boehringer Ingelheim Investigational Site
🇫🇷Strasbourg, France
205.334.1008 Boehringer Ingelheim Investigational Site
🇨🇦Kingston, Ontario, Canada
205.334.1010 Boehringer Ingelheim Investigational Site
🇨🇦Toronto, Ontario, Canada