Acute Bronchodilator Response of a Single Dose of Atrovent or Berotec on Top of Pharmacodynamic Steady State of Spiriva
Primary Purpose
Pulmonary Disease, Chronic Obstructive
Status
Completed
Phase
Phase 3
Locations
Netherlands
Study Type
Interventional
Intervention
Tiotropium + placebo
Tiotropium + ipratropium
Tiotropium + fenoterol
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive
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
Sites / Locations
- Twenteborg Ziekenhuis
- Amphia Ziekenhuis
- Boehringer Ingelheim Investigational Site
- Afdeling longziekten
- Gelre Ziekenhuizen
Outcomes
Primary Outcome Measures
Peak FEV1 response, defined as the peak FEV1 minus the steady-state baseline FEV
Secondary Outcome Measures
Peak FVC response in the six-hour observation period following administration of the first single dose of randomised treatment
FEV1 and FVC response one hour after the second dose of randomised treatment
Individual FEV1 and FVC measurements at each time point
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
All adverse events
Pulse rate
Sitting blood pressure in conjunction with spirometry
ECG recorded one hour after the first dose of randomised treatment
Physical examination at baseline (Visit 1) and at the conclusion of patient participation in the trial
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00274066
Brief Title
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
2. Study Status
Record Verification Date
October 2013
Overall Recruitment Status
Completed
Study Start Date
October 2002 (undefined)
Primary Completion Date
September 2003 (Actual)
Study Completion Date
September 2003 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Chronic Obstructive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
Double
Allocation
Randomized
Enrollment
65 (false)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Tiotropium + placebo
Intervention Type
Drug
Intervention Name(s)
Tiotropium + ipratropium
Intervention Type
Drug
Intervention Name(s)
Tiotropium + fenoterol
Primary Outcome Measure Information:
Title
Peak FEV1 response, defined as the peak FEV1 minus the steady-state baseline FEV
Time Frame
up to 37 days
Secondary Outcome Measure Information:
Title
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
Title
FEV1 and FVC response one hour after the second dose of randomised treatment
Time Frame
up to 37 days
Title
Individual FEV1 and FVC measurements at each time point
Time Frame
up to 37 days
Title
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
Title
All adverse events
Time Frame
up to 37 days
Title
Pulse rate
Time Frame
up to 37 days
Title
Sitting blood pressure in conjunction with spirometry
Time Frame
up to 37 days
Title
ECG recorded one hour after the first dose of randomised treatment
Time Frame
up to 37 days
Title
Physical examination at baseline (Visit 1) and at the conclusion of patient participation in the trial
Time Frame
up to 37 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim Study Coordinator
Organizational Affiliation
Boehringer Ingelheim BV/Alkmaar
Official's Role
Study Chair
Facility Information:
Facility Name
Twenteborg Ziekenhuis
City
Almelo
ZIP/Postal Code
7609 PP
Country
Netherlands
Facility Name
Amphia Ziekenhuis
City
Breda
ZIP/Postal Code
4819 EV
Country
Netherlands
Facility Name
Boehringer Ingelheim Investigational Site
City
Groningen
ZIP/Postal Code
9700 RB
Country
Netherlands
Facility Name
Afdeling longziekten
City
Winschoten
ZIP/Postal Code
9670 RA
Country
Netherlands
Facility Name
Gelre Ziekenhuizen
City
Zutphen
ZIP/Postal Code
7207 BA
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
17890476
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.
Results Reference
derived
Links:
URL
http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/205/205.258.pdf
Description
Related Info
URL
http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/205/205.258_literature.pdf
Description
Related Info
Learn more about this trial
Acute Bronchodilator Response of a Single Dose of Atrovent or Berotec on Top of Pharmacodynamic Steady State of Spiriva
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