Clinical trial NCT00274066: Acute Bronchodilator Response of a Single Dose of Atrovent or Berotec on Top of Pharmacodynamic Steady State of Spiriva
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2006-01-10
Enrollment: 65
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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)

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.

Eligibility criteria: 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

Primary outcomes:
measure: Peak FEV1 response, defined as the peak FEV1 minus the steady-state baseline FEV
timeFrame: up to 37 days
Secondary outcomes:
measure: Peak FVC response in the six-hour observation period following administration of the first single dose of randomised treatment
timeFrame: up to 37 days
measure: FEV1 and FVC response one hour after the second dose of randomised treatment
timeFrame: up to 37 days
measure: Individual FEV1 and FVC measurements at each time point
timeFrame: up to 37 days
measure: 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
timeFrame: up to 37 days
measure: All adverse events
timeFrame: up to 37 days
measure: Pulse rate
timeFrame: up to 37 days
measure: Sitting blood pressure in conjunction with spirometry
timeFrame: up to 37 days
measure: ECG recorded one hour after the first dose of randomised treatment
timeFrame: up to 37 days
measure: Physical examination at baseline (Visit 1) and at the conclusion of patient participation in the trial
timeFrame: up to 37 days
Other outcomes:
Locations:
city: Almelo
country: Netherlands
facility: Twenteborg Ziekenhuis
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
city: Groningen
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Winschoten
country: Netherlands
facility: Afdeling longziekten
city: Zutphen
country: Netherlands
facility: Gelre Ziekenhuizen
Study officials:
affiliation: Boehringer Ingelheim BV/Alkmaar
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References:
citation: Kerstjens HA, Bantje TA, Luursema PB, Sinninghe Damste HE, de Jong JW, Lee A, Wijker SP, Cornelissen PJ. Effects of short-acting bronchodilators added to maintenance tiotropium therapy. Chest. 2007 Nov;132(5):1493-9. doi: 10.1378/chest.06-3059. Epub 2007 Sep 21.