Acute Bronchodilator Response of a Single Dose of Atrovent or Berotec on Top of Pharmacodynamic Steady State of Spiriva

Overview

To evaluate acute effect of single dose of ipratropium (Atrovent) or fenoterol (Berotec) in comparison to placebo when given to COPD patients on pharmacodynamic steady state of tiotropium (Spiriva)

Full Title of Study: “The Acute Bronchodilator Effects of a Single Dose (2 Puffs) of the Shortacting Anticholinergic Ipratropium Bromide (40μg) and the Short-acting Beta-adrenergic Fenoterol (200μg) in Comparison to Placebo on Top of Pharmacodynamic Steady State of Once Daily Tiotropium (18μg) Inhalation Capsule in Patients With Chronic Pulmonary Disease (COPD)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Crossover Assignment
    • Primary Purpose: Treatment
    • Masking: Double
  • Study Primary Completion Date: September 2003

Detailed Description

In case mono-bronchodilator therapy does not control symptoms of COPD adequately or if regular maintenance therapy is desired, a therapeutic intervention with a combination of bronchodilators is recommended. The risks of side-effects increases with increasing dose of any drug and, therefore, the most important rationale for combination therapy is a very favourable ratio of efficacy and safety. Knowing that anticholinergic and beta-adrenergic agents achieve their bronchodilating effects by different mechanisms, in particular the combination of these agents has proven to be beneficial in the management of COPD. Based on the established clinical benefits, tiotropium is an attractive and promising agent for the first-line long-term maintenance therapy in COPD. This also implies that a therapeutic intervention with other bronchodilators will be prescribed in daily practice. At present no studies on combination therapy with short-acting agents are available. Therefore, using a double-blind, randomised, crossover design, the bronchodilator effects of single doses of ipratropium or fenoterol were compared with placebo when added on top of steady state tiotropium. Patients were pre-treated with tiotropium to achieve this pharmacodynamic steady state. Serial lung function tests (FEV1, FVC, Raw, sGaw) were conducted following add-on of the short-acting bronchodilators or placebo.

Study Hypothesis:

H0: there is no difference between treatments in mean peak FEV1 H1: there is a difference between treatments in mean peak FEV1

Comparison(s):

Add-on of placebo was compared to add-on of ipratropium or add-on of fenoterol. The comparison of ipratropium with placebo was primary. The other 2 pair-wise comparisons were secondary.

Interventions

  • Drug: Tiotropium + placebo
  • Drug: Tiotropium + ipratropium
  • Drug: Tiotropium + fenoterol

Clinical Trial Outcome Measures

Primary Measures

  • Peak FEV1 response, defined as the peak FEV1 minus the steady-state baseline FEV
    • Time Frame: up to 37 days

Secondary Measures

  • Peak FVC response in the six-hour observation period following administration of the first single dose of randomised treatment
    • Time Frame: up to 37 days
  • FEV1 and FVC response one hour after the second dose of randomised treatment
    • Time Frame: up to 37 days
  • Individual FEV1 and FVC measurements at each time point
    • Time Frame: up to 37 days
  • sGaw and Raw measured at 1 and 6 hour after the first dose of randomised treatment and at 1 hour after the second dose of randomised treatment
    • Time Frame: up to 37 days
  • All adverse events
    • Time Frame: up to 37 days
  • Pulse rate
    • Time Frame: up to 37 days
  • Sitting blood pressure in conjunction with spirometry
    • Time Frame: up to 37 days
  • ECG recorded one hour after the first dose of randomised treatment
    • Time Frame: up to 37 days
  • Physical examination at baseline (Visit 1) and at the conclusion of patient participation in the trial
    • Time Frame: up to 37 days

Participating in This Clinical Trial

Inclusion:

  • diagnosis of COPD
  • FEV1 < 60% of predicted
  • FEV1 < 70% of FVC
  • smoking history of 10 pack-years

Exclusion:

  • significant other disease than COPD
  • history of asthma, allergic rhinitis or blood eosinophil count > 600mm3
  • cardiac arrhythmia requiring drug therapy
  • symptomatic prostatic hypertrophy, bladder neck obstruction or narrow-angle glaucoma
  • recent history of MI (within past year)
  • history of cancer within past 5 years
  • life-threatening pulmonary obstruction
  • cystic fibrosis or bronchiectasis; tuberculosis
  • pulmonary resection

Gender Eligibility: All

Minimum Age: 40 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Boehringer Ingelheim
  • Overall Official(s)
    • Boehringer Ingelheim Study Coordinator, Study Chair, Boehringer Ingelheim BV/Alkmaar

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