To test our hypothesis that:The combination of the two long-acting bronchodilators indacaterol and glycopyrronium confers a superior improvement compared to nebulisation with ipratropium/salbutamol, as administered single dose in patients with…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Area under the curve (AUC) from 0 to 6 hours of FEV1 with indacaterol and
glycopyrronium, compared to nebulisation with ipratropium/salbutamol.
Secondary outcome
1. Change in Borg dyspnea score at 30 min: change in Borg score at other time
points, and proportion of patients reaching the MCID at all time points (15,
30, 60, 120 240 and 360 min) (1)
2. Changes in level of hyperinflation (by IC measurement), and proportion of
participants reaching a difference of 100 ml.
3. Time to FEV1 increase of 100 ml
4. Peak effect of FEV1 from 0 to 6 hours
5. Time to peak of FEV1
6. FEV1 at all other time points (15, 30, 60, 120 240 and 360 min)
Background summary
Patients admitted for AECOPD are in many hospitals routinely taken of their
home inhaled medication, and especially of their long-acting bronchodilators,
to be switched to 4 times daily nebulisations with ipratropium and salbutamol.
Although it has been shown in many settings that nebulisations with
bronchodilators in general convey no advantage over pMDI or dry powder (TH)
administration, this practice prevails.(1,2). Additionally, long-acting
bronchodilators have been shown to generally confer greater bronchodilation in
stable state than their short counterparts, and combinations of specific
long-acting bronchodilators have been shown to be more efficacious than the
single constituents.(3) We believe it is likely that combined long-acting
bronchodilators, are more efficacious than short acting bronchodilators per
nebulizers, especially in the onset of action. If this hypothesis can be
confirmed in stable state, this study will be repeated in an exacerbation
state. If the study shows a positive though non-significant effect of
long-acting bronchodilators, the study will also be repeated in an exacerbation
state. If the trend is in favour of short-acting medication, then the study
will not be repeated in the exacerbation state.
Study objective
To test our hypothesis that:
The combination of the two long-acting bronchodilators indacaterol and
glycopyrronium confers a superior improvement compared to nebulisation with
ipratropium/salbutamol, as administered single dose in patients with stable
state COPD.
Primary objective:
The combination of the two long-acting bronchodilators indacaterol and
glycopyrronium once daily confers a superior improvement in FEV1 as compared to
nebulisation with ipratropium/salbutamol, both administered single dose in
patients with stable state COPD.
Secondary objectives:
The combination of the two long-acting bronchodilators indacaterol and
glycopyrronium once daily confers a superior reduction in dyspnea,
hyperinflation (IC), FEV1 onset of action and peak effect compared to
nebulisation with ipratropium/salbutamol, both administered single dose in
patients with stable state COPD.
Study design
Investigator initiated, randomised, active controlled, cross-over double-blind
(and therefore double-dummy), study comparing the effects of single dose
indacaterol/glycopyrronium 110/50 Breezhaler® versus single dose
ipratropium/salbutamol nebulisation in patients with COPD in stable state.
After inclusion long-acting bronchodilators will be washed-out for at least 7
days, and randomised to receive either Ultibro + placebo nebulization or
ipratropium/salbutamol nebulization and placebo Breezhaler first, then after a
new washout period of 7 days they will receive the other treatment.
At 0 min the patient starts with Breezhaler. Nebulization starts immediately
after Breezhaler has been taken. During washout patients may use reliever
fenoterol/ipratropium max 4 times daily (20/50ug by PMDI and spacer, max 8
puffs per day) and they may continue any inhaled corticosteroids in a stable
dose, in stable state during the study. The last dose fenoterol/ipratropium is
permitted till 6 hours before the measurements.
Intervention
After inclusion long-acting bronchodilators will be washed-out for at least 7
days, and patients will be randomised to receive either Ultibro + placebo
nebulization or ipratropium/salbutamol nebulization and placebo Breezhaler
first. After a new washout period of at least 7 days they will receive the
other treatment. During the trial they will be prescribed
fenoterol/ipratropium as reliever medication.
At 0 min the patient starts with Breezhaler. Nebulization starts immediately
after Breezhaler has been taken. During washout patients may use reliever
fenoterol/ipratropium max 4 times daily (20/50ug by PMDI and spacer, max 8
puffs per day) and they may continue any inhaled corticosteroids in a stable
dose, in stable state during the study. The last dose fenoterol/ipratropium is
permitted till 6 hours before the measurements.
Study burden and risks
This study has no specific benefits for the participating patients. The study
also has no major risks. Minor risks for participants after a single dosis can
be throat irritation, cough, headache and dizziness, sinus tachycardia.
The combination of treatments with *2-agonist bronchodilators and
anticholinergic bronchodilators have been used in daily practice for many years
in many countries and they are often prescribed both in COPD. We expect that
most participants have used similar medication before, Both
indacaterol/glycopyrronium and ipratropium/salbutamol are approved for COPD
treatment in the Netherlands.
Safety aspects regarding the replacement of long-acting bronchodilators (1-2 x
daily) by short-acting (fenoterol/ipratropium 4 times daily) are deemed
negligible. Many patients are still on a regimen of short-acting
bronchodilators. Patients can continue all other drugs including inhaled
corticosteroids. Effectively participants will have access to adequate medical
treatment during the whole study.
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria:;1. COPD, post-bronchodilator FEV1/FVC < 70%; post-br FEV1 < 80%pred
2. Active mastery of Dutch
3. Written informed consent
4. At least 40 years old
5. Patients must be able to understand and complete protocol requirements, Instructions, and questionnaires provided in Dutch
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:;1. Non invasive ventilation
2. Saturation by pulse oxymetry <88%
3. Documented history of asthma
4. Instable cardiac disease within 6 months.
5. Known long QTC syndrome
6. Known EGFR <30 ml/min *1,73m2
7. Exacerbations of COPD or change of medication for COPD in the last 6 weeks prior to inclusion
8. Allergic reaction or intolerance for a substance used in one of the products or atropine or atropine derived substances
9. Pregnant or lactating females.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-000473-12-NL |
| CCMO | NL52506.042.15 |