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Trial registered on ANZCTR


Registration number
ACTRN12613000046707
Ethics application status
Approved
Date submitted
14/01/2013
Date registered
15/01/2013
Date last updated
11/12/2019
Date data sharing statement initially provided
11/12/2019
Date results provided
11/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Managing Inflammation in Chronic Obstructive Pulmonary Disease (COPD) [Mi COPD]
Scientific title
Inflammometry in people with Chronic Obstructive Pulmonary Disease (COPD) and its impact on health related quality of life and COPD exacerbations.
Secondary ID [1] 281732 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Mi COPD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease (COPD) 288036 0
Condition category
Condition code
Respiratory 288410 288410 0 0
Chronic obstructive pulmonary disease
Inflammatory and Immune System 288411 288411 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention will involve inflammation based pharmacotherapy targeted to markers of airway and systemic inflammation. The treatment decisions will be informed using a treatment decision algorithm. Both groups will be treated for 6 months. In the intervention group, neutrophilic inflammation (sputum neutrophils >age correlated absolute) will be treated with oral tablet of azithromycin 250mg daily for 6 months. Systemic inflammation (hs-CRP>3mg/l or WCC>9x10 (9)/L) will be treated with oral tablet of rosuvastatin 20mg nocte for 6 months. Eosinophilic inflammation will be treated with daily oral tablet of Prednisolone 15mg for 4 weeks and then 5mg for 20 weeks. In the case of a combination of inflammatory processes, participants will be prescribed a combination of treatments according to the algorithm. If the inflammatory process is not detected, the targeted active treatment will be substituted with a matching placebo.
Intervention code [1] 286268 0
Treatment: Drugs
Comparator / control treatment
The control group will receive usual care defined by the GOLD treatment recommendations and matching placebo 1 twice daily (bd). A random selection of 25% of participants in the control group will also receive a placebo tablet to match the Oral Corticosteroid (OCS) in the intervention group, in addition to their 1 bd placebo tablets. This proportion is determined based on our stable estimates of the prevalence of sputum eosinophilia in this population. With this treatment regimen, participants in both groups will receive 1 tablet each morning and night and 1 in 4 participants will receive an additional tablet each morning. Placebo tablets will be of identical appearance to the active medications, and formulated by an approved compounding chemist. The comparison will be the package of targeted treatment compared to control, not individual treatment comparisons.
Control group
Placebo

Outcomes
Primary outcome [1] 288580 0
Health related quality of life as assessed by the St George Respiratory Questionnaire, specifically the proportion in each group with a clinically significant improvement (>4 units).
Timepoint [1] 288580 0
Baseline, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 12 months and 18 months.
Secondary outcome [1] 300495 0
Time to first acute exacerbation of COPD. An exacerbation will be defined as "a complex of respiratory symptoms (increased or new onset) of more than one of the following cough, sputum, wheezing, dyspnoea, or chest tightness with a duration of at least 3 days requiring treatment with antibiotics or systemic steroids.
Timepoint [1] 300495 0
Duration of study.
Secondary outcome [2] 300496 0
Health status as measured by the COPD Assessment test (CAT).
Timepoint [2] 300496 0
Participants will complete the CAT daily as part of home monitoring, as well as at baseline, 1 month, 2 month, 3 month, 4 month, 5 month, 6 month, 12 month and 18 month follow ups.
Secondary outcome [3] 300497 0
Airway inflammation as measured by sputum cell counts.
Timepoint [3] 300497 0
baseline, 2 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 12 months and 18 months.
Secondary outcome [4] 300498 0
Systemic inflammation as measured by high sensitivity CRP.
Timepoint [4] 300498 0
baseline, week 2, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 12 months and 18 months.
Secondary outcome [5] 300499 0
Lung function as measured by spirometry
Timepoint [5] 300499 0
Baseline, week 2, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 12 months and 18 months.
Secondary outcome [6] 300500 0
Serum biomarkers of a panel of proteins (haptoglobin, ceruplasmin, a-2 macroglobulin (a-2M) and hemopexin will be measured by ELISA.
Timepoint [6] 300500 0
Baseline, 6 months, 12 months.

Eligibility
Key inclusion criteria
Adults with COPD, confirmed by incompletely reversible airflow obstruction (post bronchodilator FEV1 <80% predicted and FER <0.7 or physician confirmed COPD in patients with a reduced FVC), and stable disease with no recent respiratory infection, acute exacerbation, or change in maintenance therapy in the previous 4 weeks. Participants will have a history of a prior COPD exacerbation in the past year.
Minimum age
No limit
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Current smoking (confirmed by history and exhaled carbon monoxide); current treatment with any macrolide, tetracycline or OCS in the preceding month, hypersensitivity to macrolides, pregnancy/breast feeding, inability to attend study visits, impaired liver function at screening as shown by AST, ALT, alkaline phosphatase or total bilirubin greater than the 2 times upper limit of normal. Participants will be excluded if there is prolongation of the QTc interval (480mS) or significant hearing impairment.

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)
Concealed random allocation will be employed. In order to ensure optimal matching of groups, the process of stratification will be used by a third party via a computer program to randomise participants into two groups. They will be randomly assigned to receive inflammometry or matched placebo. The criteria used for stratification will include the baseline eosinophil and neutrophil count in the sputum, and baseline hs-CRP or WCC count.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
In order to ensure optimal matching of groups, the process of stratification will be used by a third party to randomise participants into two groups.
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
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Data will be analysed on an intention-to-treat basis using two-sided tests with p values <0.05 considered significant. The proportion experiencing a clinically important difference will be compared using the Chi square test at the end of treatment. Analysis of covariance will be conducted on end of treatment quality of life variables with adjustment for baseline values. Continuous variables will be analysed using a generalised linear mixed model (GLMM) with a random intercept for individuals to account for the repeated measurements on individuals. The difference in exacerbation rate between the two groups will be compared using a Poisson regression model. The time to first asthma exacerbation will be analysed using Kaplan-Meier plots and a log-rank test, with analysis of instantaneous risk described using a Cox proportional hazards model. The proportion of participants with one or more exacerbations will be compared using a Chi square test. The institute’s statistician will supervise these analyses.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
21/08/2013
Actual
22/08/2013
Date of last participant enrolment
Anticipated
30/12/2014
Actual
13/09/2016
Date of last data collection
Anticipated
Actual
10/04/2018
Sample size
Target
134
Accrual to date
Final
114
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 359 0
John Hunter Hospital Royal Newcastle Centre - New Lambton
Recruitment postcode(s) [1] 6154 0
2305 - New Lambton Heights

Funding & Sponsors
Funding source category [1] 286520 0
Government body
Name [1] 286520 0
National Health and Medical Research Council (NHMRC)
Country [1] 286520 0
Australia
Primary sponsor type
Hospital
Name
John Hunter Hospital
Address
Locked Bag 1 HRMC
NSW 2310
Country
Australia
Secondary sponsor category [1] 285308 0
University
Name [1] 285308 0
The University of Newcastle
Address [1] 285308 0
University Drive
Callaghan NSW 2308
Country [1] 285308 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288593 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 288593 0
Ethics committee country [1] 288593 0
Australia
Date submitted for ethics approval [1] 288593 0
Approval date [1] 288593 0
Ethics approval number [1] 288593 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 36850 0
A/Prof Vanessa McDonald
Address 36850 0
Department of Respiratory and Sleep Medicine, John Hunter Hospital
Level 2, West Wing, Hunter Medical Research Institute (HMRI) building
Locked Bag 1000
New Lambton NSW 2305.
Country 36850 0
Australia
Phone 36850 0
+612 40420146
Fax 36850 0
+612 40420046
Email 36850 0
Vanessa.Mcdonald@hnehealth.nsw.gov.au
Contact person for public queries
Name 36851 0
Netsanet Negewo (Netsi)
Address 36851 0
Respiratory Level 2 West HMRI Building
Locked Bag 1, HRMC
N.S.W 2310
Country 36851 0
Australia
Phone 36851 0
+612 40420762
Fax 36851 0
+61240420046
Email 36851 0
Netsanet.Negewo@uon.edu.au
Contact person for scientific queries
Name 36852 0
Vanessa McDonald
Address 36852 0
Respiratory Level 2 West HMRI Building
Locked Bag 1, HRMC
N.S.W 2310
Country 36852 0
Australia
Phone 36852 0
+612 40420146
Fax 36852 0
+612 40420046
Email 36852 0
Vanessa.Mcdonald@hnehealth.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.