Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001263987
Ethics application status
Approved
Date submitted
27/10/2020
Date registered
24/11/2020
Date last updated
24/11/2020
Date data sharing statement initially provided
24/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of maintenance macrolide antibiotic de-escalation during the Australian summer season on exacerbations of respiratory diseases such as asthma, COPD and bronchiectasis
Scientific title
The effect of macrolide antibiotic de-escalation during the Australian summer season on exacerbations of obstructive airway diseases in adults: a double-blind placebo-controlled point-of-care randomised controlled trial
Secondary ID [1] 302622 0
None
Universal Trial Number (UTN)
Trial acronym
Macrolide Antibiotic STEwardship in obstRuctive airway diseases (MASTER study)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 319515 0
Chronic obstructive pulmonary disease 319516 0
Non-cystic fibrosis bronchiectasis 319517 0
Condition category
Condition code
Respiratory 317470 317470 0 0
Asthma
Respiratory 317763 317763 0 0
Chronic obstructive pulmonary disease
Respiratory 317764 317764 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a medication de-escalation study. The intervention is ceasing the current maintenance (long-term) macrolide antibiotic during the Australian summer season. To maintain blinding, the intervention arm participants will receive a placebo after stopping the current macrolide. The dose and frequency of the study medication will be independent of the dose and frequency of the current macrolide use. All participants randomised to this arm will receive 500mg placebo tablets (administered orally) three times a week for nine months. The composition of placebo tablet includes microcrystalline cellulose, colloidal silicon dioxide, sodium starch glycolate and sodium stearyl fumarate. The self-reported adherence will be assessed at each follow-up visits.
Intervention code [1] 318931 0
Treatment: Drugs
Comparator / control treatment
The control arm participants will continue the macrolide antibiotics. However, they will stop the current macrolide antibiotic and start an equivalent macrolide which is azithromycin provided by the research team. The dose and frequency of the study medication will be independent of the dose and frequency of the current macrolide use. All participants randomised to this arm will receive 500mg azithromycin tablets (administered orally) three times a week for nine months. The self-reported adherence will be assessed at each follow-up visits.
Control group
Active

Outcomes
Primary outcome [1] 325525 0
Exacerbation rate in summer (proportions of patients experiencing at least one exacerbation during the Australian summer season will be assessed and compared between groups). The self-reported exacerbations will be assessed at each follow-up interview using a study-specific questionnaire.
Timepoint [1] 325525 0
Three months after starting the study treatment. The three-month follow-up will be conducted at the end of the summer season to evaluate the exacerbation rate in summer.
Secondary outcome [1] 388282 0
Self-reported number of hospitalisations at each follow-up
Timepoint [1] 388282 0
3-month, 6-month and 9-month
Secondary outcome [2] 388283 0
Self-reported number of emergency department visit at each follow-up
Timepoint [2] 388283 0
3-month, 6-month and 9-month
Secondary outcome [3] 388284 0
Self-reported use of corticosteroid and antibiotics at each follow-up
Timepoint [3] 388284 0
3-month, 6-month and 9-month

Eligibility
Key inclusion criteria
At least 18 years of age; currently receiving maintenance macrolide therapy (azithromycin, clarithromycin, roxithromycin or erythromycin) for the management of obstructive airway disease (asthma, COPD or bronchiectasis) for a period of at least 6 months; able to provide verbal informed consent; have access to a telephone; and willing to complete baseline and follow-up telephone interviews.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pregnant women (self-reported); patients with cystic fibrosis; the use of a macrolide for other conditions (e.g, mycobacterium avium complex infection, MAC) and unable to speak and understand English.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
24/11/2020
Actual
Date of last participant enrolment
Anticipated
30/11/2021
Actual
Date of last data collection
Anticipated
31/08/2022
Actual
Sample size
Target
160
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 307053 0
University
Name [1] 307053 0
The university of Newcastle
Country [1] 307053 0
Australia
Primary sponsor type
Government body
Name
Hunter New England Local Health District
Address
Lookout Rd, New Lambton NSW 2305
Country
Australia
Secondary sponsor category [1] 307642 0
None
Name [1] 307642 0
Address [1] 307642 0
Country [1] 307642 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307178 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 307178 0
Lookout Rd, New Lambton Heights NSW 2305
Ethics committee country [1] 307178 0
Australia
Date submitted for ethics approval [1] 307178 0
Approval date [1] 307178 0
08/10/2020
Ethics approval number [1] 307178 0

Summary
Brief summary
This study is a new initiative to promote appropriate use of long-term macrolide antibiotics such as azithromycin, clarithromycin, roxithromycin and erythromycin in the management of respiratory diseases such as asthma, COPD and non-cystic fibrosis bronchiectasis. Although these drugs are effective, it is not clear for how long the treatment should be continued. Guidelines recommend a treatment duration of 6-12 months. They also recommend a drug break each year. In this study, we are investigating whether it is possible to stop these drugs permanently or at least temporarily after undergoing a certain period of treatment.
We are looking for participants who are currently taking azithromycin, clarithromycin, roxithromycin or erythromycin for the treatment of asthma, COPD or bronchiectasis for at least 6 months. Participants will be randomised to one of the two study groups. Participants in both groups will stop the current macrolide during the Australian summer season as we anticipate that the summer season would be the best time to try medication withdrawal in respiratory diseases. After stopping the current macrolide, group 1 will start an equivalent macrolide which will be azithromycin, and group 2 will start an identical placebo. Participants will continue the study medication for a period of nine months with scheduled follow-ups at 3-, 6- and 9-months.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 106302 0
Prof Peter Gibson
Address 106302 0
Priority Research Centre for Healthy Lungs
The University of Newcastle
Hunter Medical Research Institute
Lot 1, Kookaburra Cct, New Lambton Heights NSW 2305
Country 106302 0
Australia
Phone 106302 0
+61 2 4042 0143
Fax 106302 0
Email 106302 0
[email protected]
Contact person for public queries
Name 106303 0
Dr Dennis Thomas
Address 106303 0
Priority Research Centre for Healthy Lungs
The University of Newcastle
Hunter Medical Research Institute
Lot 1, Kookaburra Cct, New Lambton Heights NSW 2305
Country 106303 0
Australia
Phone 106303 0
+61 2 4042 0199
Fax 106303 0
Email 106303 0
[email protected]
Contact person for scientific queries
Name 106304 0
Dr Dennis Thomas
Address 106304 0
Priority Research Centre for Healthy Lungs
The University of Newcastle
Hunter Medical Research Institute
Lot 1, Kookaburra Cct, New Lambton Heights NSW 2305
Country 106304 0
Australia
Phone 106304 0
+61 2 4042 0199
Fax 106304 0
Email 106304 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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.