NCT00563381 - Tiotropium Once Daily 18 Mcg Versus Salmeterol Twice Daily 50 Mcg on Time to First Exacerbation in COPD Patients. | Crick

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. All patients must have a diagnosis of chronic obstructive pulmonary disease (COPD) and must meet the following criteria at Visit 1: Patients must have relatively stable, moderate to very severe airway obstruction with a post-bronchodilator FEV1 \<=70% of predicted normal and FEV1 \<=70% of FVC post-bronchodilator (i.e. 30 minutes after inhalation of 4 puffs of 100 µg salbutamol or equivalent SABA). Predicted normal values will be calculated according to ECSC. For Height measured in inches Males: FEV1 predicted (L) = 4.30 x (height (inches) / 39.37)-0.029 x age (yrs) - 2.49 Females:FEV1 predicted (L) = 3.95 x (height (inches) / 39.37)-0.025 x age (yrs) - 2.60 For Height measured in metres Males: FEV1 predicted (L) = 4.30 x (height (metres)) - 0.029 x age (years) - 2.49 Females: FEV1 predicted (L) = 3.95 x (height (metres)) - 0.025 x age (years) - 2.60 2. All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial. 3. Male or female patients 40 years of age or older. 4. Patients with a history of at least one exacerbation within the past year requiring treatment with either antibiotics and/or systemic steroids and/or hospitalisation. 5. Patients must be current or ex-smokers with a smoking history of \>= 10 pack-years. (Patients who have never smoked cigarettes must be excluded.) 6. Patients must be able to perform all study-related procedures including technically acceptable pulmonary function tests (PFTs). 7. Patients must be able to inhale medication in a competent manner from the HandiHaler and a metered dose inhaler (MDI). 8. Patients must be able to maintain records (patient daily diary card) during the study period as required in the protocol. Exclusion Criteria: 1. Significant diseases other than COPD. A significant disease is defined as a disease or condition which, in the opinion of the investigator, may put the patient at risk because of participation in the study or may influence either the results of the study or the patients' ability to participate in the study. 2. Patients with a diagnosis of asthma. 3. Patients with a life-threatening pulmonary obstruction, or a history of cystic fibrosis. 4. Patients with known active tuberculosis. 5. Patients with a known symptomatic prostatic hyperplasia or bladder neck obstruction. Patients with symptomatically-controlled prostatic hyperplasia on medication may be included and should continue their medication. 6. Patients with known narrow-angle glaucoma. 7. Patients with a history of myocardial infarction within the year prior to Visit 1. 8. Patients with a history of hospital admission for heart failure within the year prior to Visit 1. 9. Patients with cardiac arrhythmia requiring medical or surgical treatment. 10. Patients with severe cardiovascular disorders. 11. Patients with a known hypersensitivity to anticholinergic drugs, beta-adrenergics, lactose or any other component of the medication delivery system. 12. Patients with known moderate or severe renal insufficiency (known creatinine clearance of \<= 50 mL/min). 13. Patients with untreated known hypokalaemia. 14. Patients with untreated known thyrotoxicosis. 15. Patients with brittle/unstable diabetes mellitus. 16. Patients with a history of and/or active significant alcohol or drug abuse. See exclusion criterion 1. 17. Patients who have taken an investigational drug within 30 days or six half-lives (whichever is greater) prior to Screening Visit (Visit 1). 18. Use of systemic corticosteroid medication at unstable doses (i.e less than six weeks on stable dose) or at doses in excess of the equivalent of 10 mg prednisolone per day or 20 mg every other day. 19. 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 e.g Norplant) for at least three months prior to, and for the duration of the trial. 20. Previous participation (receipt of randomised treatment) in this study. 21. Patients who are currently participating in another study. 22. Patients with any respiratory infection or COPD exacerbation in the four weeks prior to the Screening Visit (Visit 1) or during the run-in period should be postponed. In the case of a respiratory infection or COPD exacerbation during the run-in period, the latter may be extended up to four weeks.

Outcomes

Primary Outcomes

First Occurrence of (Moderate or Severe) COPD Exacerbation

First occurrence analysed by Cox regression as time to first exacerbation and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).

Time frame: 52 weeks

Secondary Outcomes

COPD Exacerbations Per Patient-year Leading to Hospitalisation

An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).

Time frame: 52 weeks

Number of Participants With at Least One COPD Exacerbation

Time frame: 52 weeks

COPD Exacerbations Per Patient-year

Time frame: 52 weeks

First Occurrence of COPD Exacerbation Leading to Hospitalization

First occurrence analysed by Cox regression as time to first exacerbation leading to hospitalisation and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).

Time frame: 52 weeks

Number of Participants With at Least One COPD Exacerbation Leading to Hospitalisation

Time frame: 52 weeks

Occurrence of Premature Discontinuation of Trial Medication

Occurrence analysed by Cox regression as time to premature discontinuation of trial medication and reported as hazard ratio

Time frame: 52 weeks

Number of Participants With Premature Discontinuation of Trial Medication

Time frame: 52 weeks

First Occurrence of COPD Exacerbation or Discontinuation of Trial Medication Because of Worsening of Underlying Disease, Whichever Comes First

First occurrence analysed by Cox regression as time to first exacerbation or discontinuation of trial medication because of worsening of underlying disease, whichever comes first and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).

Time frame: 52 weeks

First Occurrence of COPD Exacerbations Treated With Systemic Steroids

First occurrence analysed by Cox regression as time to first exacerbation treated with systemic steroids and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).

Time frame: 52 weeks

First Occurrence of COPD Exacerbations Treated With Antibiotics

First occurrence analysed by Cox regression as time to first exacerbation treated with antibiotics and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).

Time frame: 52 weeks

First Occurrence of COPD Exacerbations Treated With Systemic Steroids and Antibiotics

First occurrence analysed by Cox regression as time to first exacerbation treated with systemic steroids and antibiotics and reported as hazard ratio. An exacerbation was defined as an increase or new onset of more than 1 symptom (cough, sputum, wheezing, dyspnoea, chest tightness), with at least 1 symptom lasting at least 3 days and requiring treatment with systemic steroids and/or antibiotics (moderate exacerbation) or hospitalisation (severe exacerbation).

Time frame: 52 weeks

COPD Exacerbations Treated With Systemic Steroids Per Patient-year

Time frame: 52 weeks

COPD Exacerbations Treated With Antibiotics Per Patient-year

Time frame: 52 weeks

COPD Exacerbations Treated With Systemic Steroids and Antibiotics Per Patient-year

Time frame: 52 weeks

Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 1