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Trial registered on ANZCTR


Trial ID
ACTRN12616001208493
Ethics application status
Approved
Date submitted
24/08/2016
Date registered
1/09/2016
Date last updated
10/02/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy of umeclidinium bromide and vilanterol (UMEC/VI) for the slowing of chronic obstructive pulmonary disease (COPD) development in smokers
Scientific title
Continuous maximal bronchodilatation with UMEC/VI as first line treatment for smokers at risk of developing COPD
Secondary ID [1] 290002 0
None
Universal Trial Number (UTN)
Trial acronym
The ECOS Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease 300013 0
Condition category
Condition code
Respiratory 299907 299907 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Umeclidinium bromide 62.5mcgs with vilanterol 25 mcgs (Anoro) via Ellipta (inhalation), once daily for 12 months. Adherence will be monitored by empty drug returns.
Intervention code [1] 295710 0
Treatment: Drugs
Comparator / control treatment
Matched placebo via Ellipta, once daily for 12 months. The placebo is a white free flowing powder composed of lactose monohydrate blended with magnesium stearate to match the umeclidinium inhalation powder.
Control group
Placebo

Outcomes
Primary outcome [1] 299390 0
Rate of decline of FEV1 (expressed as mls/year), measured by spirometry, during and at the end of a 12 month intervention on active study treatment or placebo
Timepoint [1] 299390 0
Visits are conducted at 0, 6 and 12 months.
Secondary outcome [1] 327023 0
Change from baseline to 12 months in small airway function as measured by the forced oscillation technique (FOT).
Timepoint [1] 327023 0
Visits are conducted at 0, 6 and 12 months.
Secondary outcome [2] 327111 0
Change from baseline to 12 months in ventilation heterogeneity by using the multiple breath nitrogen washout (MBNW) method
Timepoint [2] 327111 0
Visits are conducted at 0, 6 and 12 months.
Secondary outcome [3] 327112 0
Change from baseline to 12 months in lung volume as measured by assessing lung diffusing capacity for carbon monoxide (DLCO).
Timepoint [3] 327112 0
Visits are conducted at 0, 6, and 12 months.
Secondary outcome [4] 327113 0
To assess the effect of bronchodilators on symptoms using the breathlessness, cough, and sputum scale (BCSS) over 12 months.
Timepoint [4] 327113 0
Visits are conducted at 0, 6, and 12 months.
Secondary outcome [5] 327114 0
To assess differences in reported adverse events between the intervention and placebo treatment groups over 12 months of treatment. Only information on the following adverse events will be collected by medical examination or participant self-report: dry mouth, visual difficulty/blurred vision, palpitations and cardiac events, tremor, pneumonia and upper respiratory tract infections, urinary symptoms or allergic reactions.
Timepoint [5] 327114 0
Visits are conducted at 0, 6 and 12 months.

Eligibility
Key inclusion criteria
1. Aged 25-45 years
2. Current and continuing smoker
3. History of 10-25 pack years tobacco exposure
4. Normal post-bronchodilator spirometry (FEV1>80% pred, FEV1/FVC>70%) or GOLD Stage 1 (FEV1>80% pred, FEV1/FVC<70%)
5. Abnormal multiple breath nitrogen washout (MBNW) (Sacin, Scond or both derived from MBNW)
6. Willingness and ability to give written informed consent
Minimum age
25 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Unable to perform the tests
2. Have had lung surgery
3.Currently have asthma, defined as a doctor diagnosis of asthma and current symptoms i.e. within 12 months prior to screening
4. Regularly used respiratory preventer/controller medication in the past 5 years
5. Have required frequent use of bronchodilator in the last 5 years (on average>once/week)
6. Have bronchiectasis
7. Have had heart failure
8. Have uncontrolled/unstable arrhythmia
9. Have an upper or lower respiratory tract infection within 6 weeks of screening
10. Cease smoking at the time of the smoking cessation intervention
11. Taking any respiratory medications or other regular medications that could affect respiratory function
12. Regularly smoke tetrahydrocannabinol (THC) >= once/week
13. Considered unlikely to be able to adhere to taking study medication over the full 12 months of the treatment period

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)
The allocation sequence will be by sequentially numbered, opaque, sealed envelopes and will be generated by the data management team at The George Institute for Global Health
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients will be allocated to treatment (placebo or active study drug) using computer-generated random numbers. There will be no stratification.
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
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Efficacy
Statistical methods / analysis

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
Current
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 6538 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 6539 0
Concord Repatriation Hospital - Concord
Recruitment hospital [3] 6540 0
Campbelltown Hospital - Campbelltown
Recruitment hospital [4] 6591 0
Woolcock Institute of Medical Research - Glebe
Recruitment postcode(s) [1] 14119 0
2065 - St Leonards
Recruitment postcode(s) [2] 14120 0
2139 - Concord
Recruitment postcode(s) [3] 14121 0
2560 - Campbelltown
Recruitment postcode(s) [4] 14198 0
2037 - Glebe

Funding & Sponsors
Funding source category [1] 294375 0
Commercial sector/Industry
Name [1] 294375 0
GlaxoSmithKline
Address [1] 294375 0
82 Hughes Avenue
Ermington
NSW 2115
Country [1] 294375 0
Australia
Primary sponsor type
Other Collaborative groups
Name
The George Institute for Global Health
Address
Level 5
1 King Street
Newtown
NSW 2042
Australia
Country
Australia
Secondary sponsor category [1] 293219 0
None
Name [1] 293219 0
Address [1] 293219 0
Country [1] 293219 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295794 0
Northern Sydney Local Health District
Ethics committee address [1] 295794 0
Research Office
Kolling Building, Level 13
Royal North Shore Hospital
Reserve Road
St Leonards
NSW 2065
Ethics committee country [1] 295794 0
Australia
Date submitted for ethics approval [1] 295794 0
30/11/2015
Approval date [1] 295794 0
14/03/2016
Ethics approval number [1] 295794 0
HREC/15/HAWKE/489

Summary
Brief summary
Cigarette smoking produces inflammation in small airways and development of emphysema in about 20-40% of susceptible individuals. The presence of small airway pathology leads to uneven distribution of ventilation in the lungs as well as excessive airway closure which may produce excessive biomechanical stress leading to further progression of pathology. These changes produce a greater than the normal age-related rate of decline of lung function as measured by the FEV1 and this can lead to the clinical features of COPD. We hypothesise that:
1. The early pathological changes can be identified by tests derived from the multiple breath nitrogen washout (MBNW) and these tests may identify individuals at risk of developing COPD.
2. Bronchodilatation will reduce airway closure and normalise the distribution of ventilation thereby reducing biomechanical stress and may thus lead to reduction in the rate of decline of lung function.
The primary objective is to asses the rate of decline of FEV1 during and at the end of a 12 month intervention with or without active study treatment.
The secondary objective is to assess the change from baseline in small airway function and ventilation heterogeneity, change in FOT, and the effect of bronchodilators on spirometry, DLCO and BCSS symptoms.
The study is a double-blind, placebo controlled, parallel design study comparing:
1. Umeclidinium bromide with vilanterol (Anoro) via the Ellipta dry powder inhalation device at a dose of 62.5mcg/25mcg once daily with
2. Matched placebo once daily
A total of 320 participants will be randomised from four centres in NSW, Australia. Subject will attend clinic visits at screening, randomisation, 26 weeks and 52 weeks. Monthly telephone calls will be made to each participant to record adverse events, concomitant medications, adherence to medication and current smoking status.
Study measurements will include spirometry pre and post bronchodilator, body plethysmography to measure lung volumes and DLCO, MBNW, FOT and BCSS symptoms.

The student t-test will be used to compare the annual rate of decline of the FEV1 between the active treatment and placebo groups. Statistical methods for analysing the secondary outcomes will be by a linear regression model adjusted for baseline measurements if applicable.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 68498 0
Prof Christine Jenkins
Address 68498 0
The George Institute for Global Health
Level 5, 1 King Street
Newtown NSW 2042 Australia
Country 68498 0
Australia
Phone 68498 0
+61 2 8052 4300
Fax 68498 0
Email 68498 0
christine.jenkins@sydney.edu.au
Contact person for public queries
Name 68499 0
Ms Francesca Tang
Address 68499 0
Woolcock Institute of Medical Research
The University of Sydney
431 Glebe Point Road
Glebe
NSW2037
Country 68499 0
Australia
Phone 68499 0
+61 2 9114 0400
Fax 68499 0
Email 68499 0
smokers@woolcock.org.au
Contact person for scientific queries
Name 68500 0
Prof Christine Jenkins
Address 68500 0
The George Institute for Global Health
Level 5, 1 King Street
Newtown NSW 2042 Australia
Country 68500 0
Australia
Phone 68500 0
+61 2 8052 4300
Fax 68500 0
Email 68500 0
christine.jenkins@sydney.edu.au