efficacy and safety of tiotropium compared to salmeterol and placebo in patients with chronic obstructive bronchitis (copd)

Conditions: Pulmonary Disease, Chronic Obstructive

Summary: the objective of this study is to compare the long-term (six month) bronchodilator efficacy and safety of tiotropium inhalation capsules, salmeterol inhalation aerosol and placebo inpatients with copd.


Eligibility criteria:
inclusion criteria: * age ≥ 40 years. * a diagnosis of relatively stable, moderate to severe copd with: * screening fev1 ≤ 60% of predicted normal value (calculated according to european community for coal and steel (eccs) criteria and screening fev1/fvc ≤ 70% * smoking history ≥ 10 pack-years (a pack-year is 20 cigarettes per day for one year or equivalent) * ability to be trained in the proper use of the handihaler® device and metered dose inhaler (mdi). * ability to perform all study related tests including the shuttle walking test, acceptable pulmonary function tests, including peak expiratory flow rate (pefr) measurements, and maintenance of diary card records. * ability to give written informed consent in accordance with good clinical practice and local regulations. exclusion criteria: * clinically significant diseases other than copd. * patients with clinically relevant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a disease listed as an exclusion criterion, will be excluded. * all patients with a serum glutamic oxaloacetic transaminase (sgot) \> 80 iu/l, serum glutamic pyruvic transaminase (sgpt) \> 80 iu/l, bilirubin \>2.0 mg/dl or creatinine \> 2.0 mg/dl will be excluded regardless of clinical condition. * a recent history (i.e., one year or less) of myocardial infarction. * any cardiac arrhythmia requiring drug therapy or hospitalisation for heart failure within the past three years. * inability to abstain from regular daytime use of oxygen therapy for more than 1 hour per day. * known active tuberculosis. * history of cancer within the last five years (excluding basal cell carcinoma) * history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis. * patients who have undergone thoracotomy with pulmonary resection. * any upper respiratory infection in the past six weeks prior to the screening visit or during the run-in period. * current participation in a pulmonary rehabilitation programme or completion of a pulmonary rehabilitation programme in the six week prior to the screening visit. * known hypersensitivity to anticholinergic drugs, salmeterol, or any of the components of the lactose powder capsule or mdi delivery systems. * known symptomatic prostatic hypertrophy or bladder neck obstruction. * patients with known narrow-angle glaucoma. * current treatment with cromolyn sodium or nedocromil sodium. * current treatment with antihistamines (h1 receptor antagonists). * oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisolone per day or 20 mg every other day. * current use of β-blocker medication. * current treatment with monoamine oxidase inhibitors or tricyclic antidepressants. * pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception. * patients with a history of asthma, allergic rhinitis or atopy or who have a total blood eosinophil count \> 600mm3. * history of and/or active significant alcohol or drug abuse. * concomitant or recent use of an investigational drug within one month or six half lives (whichever is greater) prior to the screening visit. * changes in the pulmonary therapeutic plan within the six weeks prior to the screening visit. * inability to comply with the medication restrictions specified in section 4.2 of the trial protocol