Pulmonary Disease, Chronic ObstructivePhase 3NCT00274066
Acute Bronchodilator Response of a Single Dose of Atrovent or Berotec on Top of Pharmacodynamic Steady State of Spiriva
A Phase 3 study testing Tiotropium + ipratropium and Tiotropium + fenoterol in people with Pulmonary Disease, Chronic Obstructive, run by Boehringer Ingelheim at 5 sites in Netherlands.
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) Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- Tiotropium + ipratropium and Tiotropium + fenoterol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 5 sitesNetherlands
- Study dates
- Oct 2002to Sep 2003
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- diagnosis of COPD
- FEV1 < 60% of predicted
- FEV1 < 70% of FVC
- smoking history of 10 pack-years
Who cannot join
- 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
Show all 9Show fewer
- life-threatening pulmonary obstruction
- cystic fibrosis or bronchiectasis; tuberculosis
- pulmonary resection
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Netherlands5 sites
Twenteborg Ziekenhuis
Almelo, 7609 PP
Amphia Ziekenhuis
Breda, 4819 EV
Boehringer Ingelheim Investigational Site
Groningen, 9700 RB
Afdeling longziekten
Winschoten, 9670 RA
Gelre Ziekenhuizen
Zutphen, 7207 BA
About this study
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)
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)
Read the 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.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- Tiotropium + placebo, Tiotropium + ipratropium, Tiotropium + fenoterol
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tiotropium + placeboDrug
Tiotropium + ipratropiumDrug
Tiotropium + fenoterolDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak FEV1 response, defined as the peak FEV1 minus the steady-state baseline FEV
Measured: up to 37 days
Secondary outcomes (9)
Peak FVC response in the six-hour observation period following administration of the first single dose of randomised treatment
Measured: up to 37 days
FEV1 and FVC response one hour after the second dose of randomised treatment
Measured: up to 37 days
Individual FEV1 and FVC measurements at each time point
Measured: 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
Measured: up to 37 days
All adverse events
Measured: up to 37 days
Pulse rate
Measured: up to 37 days
Sitting blood pressure in conjunction with spirometry
Measured: up to 37 days
ECG recorded one hour after the first dose of randomised treatment
Measured: up to 37 days
Physical examination at baseline (Visit 1) and at the conclusion of patient participation in the trial
Measured: up to 37 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2006 (estimated)
- Study startOct 2002
- Primary completionSep 2003
- Study completionSep 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Enrolment
- 65 participants
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Boehringer Ingelheim Study Coordinator, Study chair, Boehringer Ingelheim BV/Alkmaar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00274066
- Sponsor's protocol ID
- 205.258
- Status last verified
- Oct 2013
- First submitted
- 9 Jan 2006
- Last updated
- 1 Nov 2013
- Results posted
- No
Publications
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.
PubMed 17890476
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00274066
- Acronym / sponsor ID
- 205.258
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Oct 2002
- Primary completion
- Sep 2003 (actual)
- Study completion
- Sep 2003 (actual)
- First posted
- 10 Jan 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- diagnosis of COPD
- FEV1 < 60% of predicted
- FEV1 < 70% of FVC
- smoking history of 10 pack-years
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tiotropium + placebo | Drug | – |
| Tiotropium + ipratropium | Drug | – |
| Tiotropium + fenoterol | Drug | – |
Primary outcome
Peak FEV1 response, defined as the peak FEV1 minus the steady-state baseline FEV
Time frame: up to 37 days
9 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2013.
- Derived from this study: PubMed 17890476Kerstjens 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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim Study Coordinator study chair
Boehringer Ingelheim BV/Alkmaar
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tiotropium + ipratropium and Tiotropium + fenoterol in people with Pulmonary Disease, Chronic Obstructive, run by Boehringer Ingelheim at 5 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak FEV1 response, defined as the peak FEV1 minus the steady-state baseline FEV (time frame: up to 37 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00274066, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2013.