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

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00274066
• Other study ID #: 205.258
• Status: Completed
• Phase: Phase 3
• First received: January 9, 2006
• Last updated: October 31, 2013
• Start date: October 2002
• Est. completion date: September 2003

Study information

• Verified date: October 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: IGZ Health Inspection
• Study type: Interventional

Clinical Trial Summary

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)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: September 2003
• Est. primary completion date: September 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Tiotropium + placebo

• Tiotropium + ipratropium

• Tiotropium + fenoterol

Locations

Country	Name	City	State
Netherlands	Twenteborg Ziekenhuis	Almelo
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	Boehringer Ingelheim Investigational Site	Groningen
Netherlands	Afdeling longziekten	Winschoten
Netherlands	Gelre Ziekenhuizen	Zutphen

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak FEV1 response, defined as the peak FEV1 minus the steady-state baseline FEV		up to 37 days	No
Secondary	Peak FVC response in the six-hour observation period following administration of the first single dose of randomised treatment		up to 37 days	No
Secondary	FEV1 and FVC response one hour after the second dose of randomised treatment		up to 37 days	No
Secondary	Individual FEV1 and FVC measurements at each time point		up to 37 days	No
Secondary	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		up to 37 days	No
Secondary	All adverse events		up to 37 days	No
Secondary	Pulse rate		up to 37 days	No
Secondary	Sitting blood pressure in conjunction with spirometry		up to 37 days	No
Secondary	ECG recorded one hour after the first dose of randomised treatment		up to 37 days	No
Secondary	Physical examination at baseline (Visit 1) and at the conclusion of patient participation in the trial		up to 37 days	No

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