Official Title: “The Acute Bronchodilator Effects of a Single Dose (2 Puffs) of the Short-Acting Anticholinergic Ipratropium Bromide (40 Mcg) and the Short-Acting Beta-Adrnergic Fenoterol (200 Mcg) in Comparison to Placebo on Top of Pharmacodynamic Steady State of Once-Daily Tiotropium (18 Mcg) Inhalation Capsule in”

To evalute 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)

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Efficacy Study

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 wit hother bronchodilators will be prescribed i ndaily practise. 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.

Intervention(s) in this Clinical Trial

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

Primary Measures

• In terms of peak as well as duration of the bronchodilatory effect, add-on therapy of fenoterol on top of tiotropium was found to be superior compared to added ipratropium.

Secondary Measures

• The safety profile indicates that adding single doses of fenoterol or ipratropium to steady state of tiotropium is safe and well tolerated.

• 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 bronchietasis; tuberculosis;
• pulmonary resection.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Boehringer Ingelheim Pharmaceuticals

Overall Clinical Trial Officials and Contacts

Boehringer Ingelheim Study Coordinator Study Chair Boehringer Ingelheim BV/Alkmaar  

Information obtained from ClinicalTrials.gov on October 15, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00274066

Study ID Number: 205.258

ClinicalTrials.gov Identifier: NCT00274066

Health Authority: Netherlands: IGZ Health Inspection