Trial Review

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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
Sex
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
21/01/2015
Actual
18/02/2015
Date of last participant enrolment
Anticipated
17/02/2017
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
25
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
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
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
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
[email protected]
Contact person for public queries
Name 54151 0
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
[email protected]
Contact person for scientific queries
Name 54152 0
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
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Milne S, Hammans C, Watson S, Farah CS, Thamrin C,... [More Details]

Documents added automatically
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