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Completed

NCT Number: NCT00563381

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

This is a randomised, double-blind, double-dummy, multinational, multicentre, parallel group trial comparing tiotropium (18 mcg) inhalation capsule via HandiHaler and salmeterol (50 mcg) via MDI in patients with COPD. There will be a two-week run-in period followed by a 52-week randomised treatment phase. Patients who withdraw prematurely from trial medication will be encouraged to remain in the trial and participate in follow-up telephone contacts until their predicted normal exit date from the trial (i.e. 52 weeks after taking the first dose of randomised treatment). The phone calls will be made at all scheduled visits.

The primary objective of this study is to compare the effect of tiotropium (18 mcg) inhalation capsule via HandiHaler with that of salmeterol (50 mcg) via MDI on COPD exacerbations.

The primary endpoint is time to first COPD exacerbation during the 52 week randomised treatment period. A COPD exacerbation will be defined as a complex of respiratory events / symptoms (increase or new onset) of more than one of the following: cough, sputum, wheezing, dyspnoea or chest tightness with at least one symptom lasting at least three days requiring treatment with antibiotics and/or systemic steroids and/or hospitalisation.

The onset of an exacerbation is defined as the onset of the first new or increased reported symptom. The end of the exacerbation should be recorded as defined by the investigator.

Only COPD exacerbations with onset during randomised treatment will be included in the analysis.

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Key information

Conditions

Pulmonary Disease, Chronic Obstructive Chronic Disease Disease Attributes Lung Diseases Lung Diseases, Obstructive Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

205.389.1020 Boehringer Ingelheim Investigational Site, Feldbach, Austria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

  • All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial.
  • Male or female patients 40 years of age or older.
  • 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.
  • Patients must be current or ex-smokers with a smoking history of >= 10 pack-years. (Patients who have never smoked cigarettes must be excluded.)
  • Patients must be able to perform all study-related procedures including technically acceptable pulmonary function tests (PFTs).
  • Patients must be able to inhale medication in a competent manner from the HandiHaler and a metered dose inhaler (MDI).
  • Patients must be able to maintain records (patient daily diary card) during the study period as required in the protocol.

Exclusion criteria

  • 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.
  • Patients with a diagnosis of asthma.
  • Patients with a life-threatening pulmonary obstruction, or a history of cystic fibrosis.
  • Patients with known active tuberculosis.
  • 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.
  • Patients with known narrow-angle glaucoma.
  • Patients with a history of myocardial infarction within the year prior to Visit 1.
  • Patients with a history of hospital admission for heart failure within the year prior to Visit 1.
  • Patients with cardiac arrhythmia requiring medical or surgical treatment.
  • Patients with severe cardiovascular disorders.
  • Patients with a known hypersensitivity to anticholinergic drugs, beta-adrenergics, lactose or any other component of the medication delivery system.
  • Patients with known moderate or severe renal insufficiency (known creatinine clearance of <= 50 mL/min).
  • Patients with untreated known hypokalaemia.
  • Patients with untreated known thyrotoxicosis.
  • Patients with brittle/unstable diabetes mellitus.
  • Patients with a history of and/or active significant alcohol or drug abuse. See exclusion criterion 1.
  • Patients who have taken an investigational drug within 30 days or six half-lives (whichever is greater) prior to Screening Visit (Visit 1).
  • 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.
  • 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.
  • Previous participation (receipt of randomised treatment) in this study.
  • Patients who are currently participating in another study.
  • 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.

Treatment and study plan

Tiotropium Bromide

Drug

18 mcg/daily

Salmeterol

Drug

100 mcg/daily

Placebo Salmeterol

Drug

Placebo identical to Salmeterol device

Placebo Tiotropium

Drug

Placebo identical to Tiotropium device

Primary outcomes

  1. First Occurrence of (Moderate or Severe) COPD Exacerbation

    Time frame: 52 weeks

    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).

Secondary outcomes

  1. COPD Exacerbations Per Patient-year Leading to Hospitalisation

    Time frame: 52 weeks

    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).

  2. Number of Participants With at Least One COPD Exacerbation

    Time frame: 52 weeks

    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).

  3. COPD Exacerbations Per Patient-year

    Time frame: 52 weeks

  4. First Occurrence of COPD Exacerbation Leading to Hospitalization

    Time frame: 52 weeks

    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).

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

    Time frame: 52 weeks

    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).

  6. Occurrence of Premature Discontinuation of Trial Medication

    Time frame: 52 weeks

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

  7. Number of Participants With Premature Discontinuation of Trial Medication

    Time frame: 52 weeks

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

    Time frame: 52 weeks

    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).

  9. First Occurrence of COPD Exacerbations Treated With Systemic Steroids

    Time frame: 52 weeks

    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).

  10. First Occurrence of COPD Exacerbations Treated With Antibiotics

    Time frame: 52 weeks

    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).

  11. First Occurrence of COPD Exacerbations Treated With Systemic Steroids and Antibiotics

    Time frame: 52 weeks

    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).

  12. COPD Exacerbations Treated With Systemic Steroids Per Patient-year

    Time frame: 52 weeks

    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).

  13. COPD Exacerbations Treated With Antibiotics Per Patient-year

    Time frame: 52 weeks

    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).

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

    Time frame: 52 weeks

    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).

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

    Time frame: 16 weeks

    PEFR means peak expiratory flow rate and is measured in liter per minute

  16. Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 2

    Time frame: 16 weeks

    PEFR means peak expiratory flow rate and is measured in liter per minute

  17. Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 3

    Time frame: 16 weeks

    PEFR means peak expiratory flow rate and is measured in liter per minute

  18. Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 4

    Time frame: 16 weeks

    PEFR means peak expiratory flow rate and is measured in liter per minute

  19. Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 5

    Time frame: 16 weeks

    PEFR means peak expiratory flow rate and is measured in liter per minute

  20. Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 6

    Time frame: 16 weeks

    PEFR means peak expiratory flow rate and is measured in liter per minute

  21. Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 7

    Time frame: 16 weeks

    PEFR means peak expiratory flow rate and is measured in liter per minute

  22. Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 8

    Time frame: 16 weeks

    PEFR means peak expiratory flow rate and is measured in liter per minute

  23. Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 9

    Time frame: 16 weeks

    PEFR means peak expiratory flow rate and is measured in liter per minute

  24. Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 10

    Time frame: 16 weeks

    PEFR means peak expiratory flow rate and is measured in liter per minute

  25. Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 11

    Time frame: 16 weeks

    PEFR means peak expiratory flow rate and is measured in liter per minute

  26. Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 12

    Time frame: 16 weeks

    PEFR means peak expiratory flow rate and is measured in liter per minute

  27. Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 13

    Time frame: 16 weeks

    PEFR means peak expiratory flow rate and is measured in liter per minute

  28. Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 14

    Time frame: 16 weeks

    PEFR means peak expiratory flow rate and is measured in liter per minute

  29. Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 15

    Time frame: 16 weeks

    PEFR means peak expiratory flow rate and is measured in liter per minute

  30. Pre-dose Morning PEFR Measured by Patients at Home During the First Four Months of Randomised Treatment (Weekly Means Will be Calculated), Week 16

    Time frame: 16 weeks

    PEFR means peak expiratory flow rate and is measured in liter per minute

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Collaborators

  • Pfizer

Registry information

Official study title

Effect of Inhalation of Tiotropium Once Daily 18 Mcg Versus Salmeterol Twice Daily 50 Mcg on Time to First Exacerbation in COPD Patients (a Randomised, Double-blind, Double-dummy, Parallel Group, One-year Study).

Important dates

Study start
2008
Primary completion
2010
First posted
Nov 26, 2007
Registry last updated
Dec 24, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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