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Trial registered on ANZCTR


Registration number
ACTRN12615000336583
Ethics application status
Approved
Date submitted
22/01/2015
Date registered
14/04/2015
Date last updated
14/04/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Effects Of Dual, Inhaled Long-Acting Bronchodilators on Complex Lung Mechanics in Chronic Obstructive Pulmonary Disease
Scientific title
The effects of administration of dual long-acting bronchodilators (beta-agonists and muscarinic-antagonists), compared to mono therapy, on complex lung mechanics in patients with mild to moderate chronic obstructive pulmonary disease
Secondary ID [1] 286042 0
Nil
Universal Trial Number (UTN)
U1111-1166-4714
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease 294019 0
Condition category
Condition code
Respiratory 294319 294319 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
At each of the four study visits, participants will have baseline lung function and complex lung mechanics (forced oscillation technique [FOT] and multiple breath nitrogen washout [MBNW]) measured. They will then be administered a single dose of either indacaterol 150 microg, glycopyrronium 50 microg, glycopyrronium/indacaterol 50/110 microg combination, or salmeterol 50 microg, via oral inhalation route. The lung function and complex lung mechanics will then be repeated at pre-specified time intervals up to 2 hours post-administration. Each study visit will be separated by a period of at least 48 hours to ensure washout of the previous medication.
Intervention code [1] 291030 0
Treatment: Drugs
Comparator / control treatment
Each participant acts as their own control. The post-bronchodilator lung function measurements are compared to the pre-bronchodilator values at each visit.
Control group
Active

Outcomes
Primary outcome [1] 294120 0
The change in forced oscillation technique (FOT) parameters (resistance and reactance) following administration of combination glycopyrronium/indacaterol compared to glycopyrronium alone
Timepoint [1] 294120 0
2 hours post-administration at each study visit
Primary outcome [2] 294121 0
The change in forced oscillation technique (FOT) parameters (resistance and reactance) following administration of combination glycopyrronium/indacaterol compared to indacaterol alone
Timepoint [2] 294121 0
2 hours post-administration at each study visit
Secondary outcome [1] 312552 0
Mean FOT parameters (resistance and reactance) following administration of glycopyrronium/indacaterol combination, compared to pre-bronchodilator values
Timepoint [1] 312552 0
2 hours post-administration at each study visit
Secondary outcome [2] 312553 0
The change in MBNW parameters (lung clearance index, Sacin and Scond) following administration of combination glycopyrronium/indacaterol compared to glycopyrronium alone
Timepoint [2] 312553 0
2 hours post-administration at each study visit
Secondary outcome [3] 312554 0
The change in MBNW parameters (lung clearance index, Sacin and Scond) following administration of combination glycopyrronium/indacaterol compared to indacaterol alone
Timepoint [3] 312554 0
2 hours post-administration at each study visit
Secondary outcome [4] 312555 0
Mean MBNW parameters (lung clearance index, Sacin and Scond) following administration of glycopyrronium/indacaterol combination, compared to pre-bronchodilator values
Timepoint [4] 312555 0
2 hours post-administration at each study visit
Secondary outcome [5] 313981 0
The time course of change in forced oscillation technique (FOT) parameters (resistance and reactance at each of the pre-specified time points) following administration of indacaterol compared to salmeterol
Timepoint [5] 313981 0
1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 60, 90, 120 minutes post-administration at each study visit

Eligibility
Key inclusion criteria
Adults with physician-diagnosed mild-moderate chronic obstructive pulmonary disease, with a history of current or past smoking (total exposure > 10 pack years)
Minimum age
40 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Use of glycopyrronium, indacaterol, salmeterol or any other LAMA or LABA within the previous 4 weeks (unless able to undergo a 2 week washout period)
* Documented hypersensitivity to, or intolerance of, beta-agonists or anti-cholinergic therapies
* Significant respiratory infection or documented exacerbation of COPD within the previous 6 weeks
* Other active or chronic respiratory pathologies (for example, interstitial lung disease, asthma, chest wall pathology causing ventilatory restriction)
* Past history of lung surgery (including lobectomy or pneumonectomy, but not lung biopsy) or thoracic radiation therapy (excluding isolated mediastinal radiation therapy with no evidence of subsequent pulmonary fibrosis)
* Any major comorbidities deemed to impact on respiratory physiology or symptoms, including severe on uncontrolled heart failure, morbid obesity, muscular or neurological disorders causing respiratory muscle weakness or dysfunctional swallowing
* History of severe renal or hepatic impairment
* Unable to perform lung function testing at the enrollment visit
* Dependence on domiciliary supplemental oxygen, unable to go without for at least 1 hour
* Women who are breast feeding, pregnant, or unwilling to avoid pregnancy during the study period
* Unable to provide informed consent
* Current enrolment in other trials

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Eligibility determined by the lead investigator and informed consent obtained. The study is non-blinded and there is no allocation concealment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The study medications will be administered in a random order according to a computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Salmeterol (comparison with indacaterol) is unblinded due to the nature of the medication delivery (different inhaler devices). Indacaterol, glycopyrronium and the indacaterol/glycopyrronium combination are blinded.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
* Power calculations are based on pharmacodynamic data of indacaterol published by Bauwens et al. This data showed an 12% increase in the mean peak FVC (a better correlate of small airway function than FEV1) following a single 150 microgram dose of indacaterol administered via Breezhaler. Using a unimean power calculation (at a power of 80% and a significance of 0.05), the number of subjects required to detect this increase is 25.
* The change in mean FOT and MBNW parameters between pre- and post-bronchodilator testing will be analysed by paired t-test
* The relationship between change in FOT/MBNW parameters following glycopyrronium/indacaterol combination administration, indacaterol and glycopyrronium mono-administration will be assessed by 2-way repeated measures ANOVA
* The relationship between the time course of FOT parameter changes for indacaterol and salmeterol will be assessed by a mixed-effects model, as well as mean area under the curve by paired t-test

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 3363 0
Concord Repatriation Hospital - Concord
Recruitment postcode(s) [1] 9146 0
2137 - Concord

Funding & Sponsors
Funding source category [1] 290631 0
Charities/Societies/Foundations
Name [1] 290631 0
Woolcock Institute of Medical Research
Address [1] 290631 0
431 Glebe Point Rd,
GLEBE NSW 2037
Country [1] 290631 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Woolcock Institute of Medical Research
Address
431 Glebe Point Rd,
GLEBE NSW 2037
Country
Australia
Secondary sponsor category [1] 289323 0
None
Name [1] 289323 0
Address [1] 289323 0
Country [1] 289323 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292263 0
Sydney Local Health District HREC - Concord
Ethics committee address [1] 292263 0
Executive Unit, KGV Building
Royal Prince Alfred Hospital
Missenden Rd,
CAMPERDOWN NSW 2050
Ethics committee country [1] 292263 0
Australia
Date submitted for ethics approval [1] 292263 0
25/08/2014
Approval date [1] 292263 0
11/11/2014
Ethics approval number [1] 292263 0
HREC/14/CRGH/179

Summary
Brief summary
This projects aims to study the effects of different inhaled bronchodilator medications used in the management of COPD. Clinical trials have demonstrated their effects on the large airways of the lungs, however their effects on the small airways are not yet known. This project will use sensitive tests of small airway function to identify the effects of bronchodilator therapy on the small airways in COPD. Specifically, we aim to determine if two different classes of bronchodilators have a greater effect when given in combination than when given alone. We hope to use this information to enhance our knowledge of how these medications work, which may help us improve the treatment of patients with COPD.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 54150 0
A/Prof Greg King
Address 54150 0
Woolcock Institute of Medical Research 431 Glebe Point Road, Glebe NSW 2037
Country 54150 0
Australia
Phone 54150 0
+61 2 9114 0000
Fax 54150 0
Email 54150 0
ggk@woolcock.org.au
Contact person for public queries
Name 54151 0
Dr Stephen Milne
Address 54151 0
Woolcock Institute of Medical Research 431 Glebe Point Road, Glebe NSW 2037
Country 54151 0
Australia
Phone 54151 0
+61 2 9114 0000
Fax 54151 0
Email 54151 0
stephen.milne@woolcock.org.au
Contact person for scientific queries
Name 54152 0
Dr Stephen Milne
Address 54152 0
Woolcock Institute of Medical Research 431 Glebe Point Road, Glebe NSW 2037
Country 54152 0
Australia
Phone 54152 0
+61 2 9114 0000
Fax 54152 0
Email 54152 0
stephen.milne@woolcock.org.au

No information has been provided regarding IPD availability
Summary results
No Results