ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12616001208493

Ethics application status

Approved

Date submitted

24/08/2016

Date registered

1/09/2016

Date last updated

11/10/2021

Date data sharing statement initially provided

26/07/2019

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]

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

Condition category

Condition code

Respiratory

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]

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]

FEV1 (post-bronchodilator) change (mls) from baseline to month 6 after randomisation to active or placebo inhaled medication

Timepoint [1]

6 months

Secondary outcome [1]

Change from baseline to 6 and 12 months in small airway function as measured by forced oscillation technique (FOT)

Timepoint [1]

Visits are conducted at 0, 6 and 12 months.

Secondary outcome [2]

Change from baseline to 6 and 12 months in lung volume as measured by assessing lung diffusing capacity for carbon monoxide (DLCO)

Timepoint [2]

Visits are conducted at 0, 6, and 12 months.

Secondary outcome [3]

To assess the effect of bronchodilators on symptoms using the breathlessness, cough, and sputum scale (BCSS) at 6 and 12 months

Timepoint [3]

Visits are conducted at 0, 6, and 12 months.

Secondary outcome [4]

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 [4]

Visits are conducted at 0, 6 and 12 months.

Secondary outcome [5]

Rate of decline of post-bronchodilator FEV1 (expressed as mls/year) following a 12-month intervention on active versus placebo inhaler

Timepoint [5]

12 months

Secondary outcome [6]

Change in % predicted FEV1 (calculated at post bronchodilator) at 6 and 12 months

Timepoint [6]

6 and 12 months

Secondary outcome [7]

Change in pre and post bronchodilator FEV1 (L) at 6 and 12 months

Timepoint [7]

6 and 12 months

Secondary outcome [8]

Change from baseline to 6 and 12 months in lung volume as measured by assessing Lung Diffusing Capacity adjusted for alveolar volume (KCO)

Timepoint [8]

6 and 12 months

Secondary outcome [9]

Change in pre and post bronchodilator FEV1/FVC at 6 and 12 months

Timepoint [9]

0, 6 and 12 months

Eligibility

Key inclusion criteria

1. Aged 25-55 years
2. Current and continuing smoker
3. History of greater or equal to 10 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

55 Years

Sex

Both males and females

Can healthy volunteers participate?

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

Stopped early

Data analysis

Data collected is being analysed

Reason for early stopping/withdrawal

Participant recruitment difficulties

Date of first participant enrolment

Anticipated

5/09/2016

Actual

19/12/2016

Date of last participant enrolment

Anticipated

31/12/2019

Actual

4/02/2020

Date of last data collection

Anticipated

31/01/2021

Actual

28/01/2021

Sample size

Target

320

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Concord Repatriation Hospital - Concord

Recruitment hospital [2]

Campbelltown Hospital - Campbelltown

Recruitment hospital [3]

Woolcock Institute of Medical Research - Glebe

Recruitment hospital [4]

Blacktown Hospital - Blacktown

Recruitment hospital [5]

Royal North Shore Hospital - St Leonards

Recruitment postcode(s) [1]

2139 - Concord

Recruitment postcode(s) [2]

2560 - Campbelltown

Recruitment postcode(s) [3]

2037 - Glebe

Recruitment postcode(s) [4]

2148 - Blacktown

Recruitment postcode(s) [5]

2065 - St Leonards

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

GlaxoSmithKline

Address [1]

82 Hughes Avenue
Ermington
NSW 2115

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Northern Sydney Local Health District

Ethics committee address [1]

Research Office
Kolling Building, Level 13
Royal North Shore Hospital
Reserve Road
St Leonards
NSW 2065

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

30/11/2015

Approval date [1]

14/03/2016

Ethics approval number [1]

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 100 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

https://woolcock.org.au/ecos/

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Christine Jenkins

Address

The George Institute for Global Health
Level 5, 1 King Street
Newtown NSW 2042 Australia

Country

Australia

Phone

+61 2 8052 4300

Fax

christine.jenkins@sydney.edu.au

Contact person for public queries

Name

Tanya Badal

Address

Woolcock Institute of Medical Research
The University of Sydney
431 Glebe Point Road
Glebe
NSW2037

Country

Australia

Phone

+61 2 9114 0400

Fax

smokers@woolcock.org.au

Contact person for scientific queries

Name

Christine Jenkins

Address

The George Institute for Global Health
Level 5, 1 King Street
Newtown NSW 2042 Australia

Country

Australia

Phone

+61 2 8052 4300

Fax

christine.jenkins@sydney.edu.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

To retain participant privacy we only obtain de-identified information in our CRF. The data published at the end of the study will not be individual data, only summary intervention/placebo data.

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	The effect of oxygen and carbon dioxide cross-sensitivity sensor error in the Eco Medics Exhalyzer D device on measures of conductive and acinar airway function.	2022	https://dx.doi.org/10.1183/23120541.00614-2021

N.B. These documents automatically identified may not have been verified by the study sponsor.

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Documents added manually

Documents added automatically