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Trial registered on ANZCTR


Registration number
ACTRN12609000197235
Ethics application status
Approved
Date submitted
6/03/2009
Date registered
20/04/2009
Date last updated
10/03/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
The AMAZES Study: Asthma and Macrolides: the Azithromycin Efficacy and Safety Study
Scientific title
A large-scale, multicentre, double-blind, placebo controlled randomised trial to compare the efficacy (and safety) of the addition of oral low dose azithromycin for 48 weeks with fixed dose maintenance therapy on the incidence of asthma exacerbations and clinical asthma status in people with persistent asthma
Secondary ID [1] 288734 0
Nil known
Universal Trial Number (UTN)
Trial acronym
AMAZES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 4406 0
Condition category
Condition code
Respiratory 4659 4659 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Azithromycin 500mg (2 x 250mg tablets to be administered by the oral route) three times weekly for 48 weeks
Intervention code [1] 4139 0
Treatment: Drugs
Comparator / control treatment
Placebo (lactose, cellulose, magnesium dihydrate) (2x250mg tablets to be administered by the oral route) three times weekly for 48 weeks
Control group
Placebo

Outcomes
Primary outcome [1] 5525 0
The primary outcome will be asthma exacerbations in people with non-eosinophilic asthma (NEA).
Asthma exacerbations will be defined as ‘severe’ or ‘moderate’ according to the ATS/ERS Asthma Outcomes Taskforce guidelines.
A ‘severe’ exacerbation will be defined as a participant who requires:
• Use of systemic corticosteroids, or an increase from a stable systemic corticosteroid maintenance dose, for at least 3 days. (Courses of corticosteroids separated by 1 week or more will be treated as separate severe exacerbations);
• Hospitalisation or an emergency department visit requiring systemic corticosteroids.
A ‘moderate’ exacerbation will be defined as a participant who has/requires:
• Emergency department visit for asthma, not requiring systemic corticosteroids OR;
• A temporary change in preventer treatment (ICS, OR ICS/LABA) or commencement of antibiotics
AND at least one of the following:
– Deterioration in asthma symptoms for at least 2 days;
– Deterioration in lung function for at least 2 days;
– Increased rescue bronchodilator use for at least 2 days
Total number of exacerbations will constitute ‘severe’ plus ‘moderate’ exacerbations. Asthma exacerbation data will be collected at 6-weekly clinical assessments, follow-up phone calls, patient diary and by review of medical records.
Timepoint [1] 5525 0
Assessed at randomisation, 6-weekly clinical assessments and 3-weekly follow-up phone calls during treatment (48 week period). Assessed during 48-week follow-up period by 12-weekly clinical assessment and 6-weekly phone calls.
Primary outcome [2] 5526 0
Health status, assessed using the Juniper Asthma Quality of Life Questionnaire (AQLQ).
Timepoint [2] 5526 0
Assessed at randomisation and 6-weekly clinical assessments during 48-week treatment period and 12-weekly clinical assessments during 48-week post-treatment period.
Secondary outcome [1] 9309 0
Safety - Monitoring for occurrence of sensorineural deafness
Timepoint [1] 9309 0
Assessment by questioning at 6 weekly clinical assessment and 3-weekly phone calls during treatment. Initially, a small subset of patients will be subject to audiometry before and after treatment if previously sustained significant hearing loss is indicated at screening. Hearing status in all other participants is to be monitored by questionning.
Secondary outcome [2] 9372 0
Symptoms, assessed using a symptom diary and the Juniper Asthma Control Questionnaire [ACQ(6)]
Timepoint [2] 9372 0
Symptom diary will be issued at randomisation and reviewed at 6-weekly clinical assessments. ACQ(6) will be assessed at randomisation, 6-weekly clinical assessments and 3 weekly follow-up phone calls during treatment period and at 12-weekly clinical assessments and 6-weekly phone calls during 48-week post-treatment period.
Secondary outcome [3] 9373 0
Safety - Microbiology surveillance and monitoring for clinically significant azithromycin resistance. Assessed via culture of induced sputum and throat/nose swabs. Colony counting and identification by Pathology Service.
Timepoint [3] 9373 0
Assessment at randomisation, end of treatment (48 weeks) and end of post-treatment phase (96 weeks).

Eligibility
Key inclusion criteria
Symptomatic stable asthma [ACQ(6) > 0.75], confirmed variable airflow obstruction, maintenance combination therapy
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Forced expiratory volume in 1 second (FEV1) < 40% predicted. Hypersensitivity to macrolides. Other respiratory disease. Taking macrolide, tetracycline, antibiotic or oral corticosteroid in preceeding month. Taking antacid treatment. Taking medication that prolongs heart's corrected QT interval (QTc). QTc prolongation > 0.44s. Existing ECG abnormalities that may lead to arrythmias. Taking medication that will interact with azithromycin in regard to rhabdomyolosis. Current smoking (or having quit within 1 year of study entry). Significant smoking related airspace disease. Cold or respiratory tract infection within 4 weeks of study entry. Pregnancy, breast feeding, possibility of becoming pregnant (unwilling to use additional form of contraception, besides contraceptive pill, during first 2 months of treatment). Impaired liver function. Ocular, abdominal, chest or brain surgery within 3 months prior to study entry. Lung cancer or other blood, lymphatic or solid organ malignancy. Cerebral, aortic or abdominal aneurysm. Inability to attend study visits. Participation in another investigative drug study within 4 weeks of study entry.

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)
Randomised by pharmacy/research staff using random number list, concealed from investigators by manufacturing identical active and placebo tablets and labelling in a non-identifying manner.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA

Funding & Sponsors
Funding source category [1] 4589 0
Government body
Name [1] 4589 0
National Health and Medical Research Council
Address [1] 4589 0
GPO Box 1421 Canberra City ACT 2601
Country [1] 4589 0
Australia
Primary sponsor type
Government body
Name
Hunter New England Area Health Service
Address
Locked Bag 1, Hunter Region Mail Centre, Newcastle NSW 2310
Country
Australia
Secondary sponsor category [1] 4138 0
None
Name [1] 4138 0
Address [1] 4138 0
Country [1] 4138 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6637 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 6637 0
Hunter New England Area Health Service Locked Bag 1, Hunter Region Mail Centre, Newcastle NSW 2310
Ethics committee country [1] 6637 0
Australia
Date submitted for ethics approval [1] 6637 0
31/10/2008
Approval date [1] 6637 0
11/12/2008
Ethics approval number [1] 6637 0
08/11/19/3.03
Ethics committee name [2] 6640 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [2] 6640 0
Level 3, Hanson Institute
IMVS Building North Terrace
Adelaide, SA 5000
Ethics committee country [2] 6640 0
Australia
Date submitted for ethics approval [2] 6640 0
Approval date [2] 6640 0
Ethics approval number [2] 6640 0
Ethics committee name [3] 6859 0
Princess Alexandra Hospital Human Research Ethics Committee
Ethics committee address [3] 6859 0
Princess Alexandra Hospital
Ipswich Rd, Woolloongabba
QLD, 4102
Ethics committee country [3] 6859 0
Australia
Date submitted for ethics approval [3] 6859 0
12/01/2009
Approval date [3] 6859 0
Ethics approval number [3] 6859 0
Ethics committee name [4] 6860 0
The Prince Charles Hospital Human Research Ethics Committee
Ethics committee address [4] 6860 0
The Prince Charles Hospital
Research, Ethics and Governance Unit
Building 12, Rode Rd
Chermside, QLD, 4032
Ethics committee country [4] 6860 0
Australia
Date submitted for ethics approval [4] 6860 0
Approval date [4] 6860 0
Ethics approval number [4] 6860 0
HREC/08/QPCH/4
Ethics committee name [5] 6861 0
Sir Charles Gairdner Group Human Research Ethics Committee
Ethics committee address [5] 6861 0
1st Floor, E Block
Sir Charles Gairdner Hospital
Hospital Avenue
Nedlands WA 6009
Ethics committee country [5] 6861 0
Australia
Date submitted for ethics approval [5] 6861 0
Approval date [5] 6861 0
Ethics approval number [5] 6861 0
2008-147

Summary
Brief summary
Certain types of asthmatics do not respond well to usual medications. It is likely that this is due to the type of inflammatory cells found in the airways. Asthmatics with low levels of eosinophils and high levels of neutrophils may respond better if treated with a class of antibiotics called macrolides. Long-term use of macrolides helps people with a variety of types of inflammation in the lung. As yet, it is unknown whether this will help in asthmatics. The main purpose of this study is to see whether taking two Azithromycin (a macrolide) tablets three times per week for 48 weeks will help people with asthma. It is hypothesised that taking the Azithromycin will reduce the number of asthma exacerbations (or 'attacks'), decrease the general daily symptoms experienced and improve health status.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 800 800 0 0

Contacts
Principal investigator
Name 29339 0
Prof Peter Gibson
Address 29339 0
Respiratory and Sleep Medicine, Level 2 West Hunter Medical Research Institute
Locked bag 1000
New Lambton Heights NSW 2305
Country 29339 0
Australia
Phone 29339 0
+61 2 4042 0143
Fax 29339 0
Email 29339 0
peter.gibson@hnehealth.nsw.gov.au
Contact person for public queries
Name 12586 0
Ms Deborah Hall
Address 12586 0
Respiratory and Sleep Medicine, Level 2 West Hunter Medical Research Institute
Locked bag 1000
New Lambton Heights NSW 2305
Country 12586 0
Australia
Phone 12586 0
+61 2 4042 0142
Fax 12586 0
+61 2 4042 0046
Email 12586 0
deborah.hall@hnehealth.nsw.gov.au
Contact person for scientific queries
Name 3514 0
Prof Professor Peter Gibson
Address 3514 0
Respiratory and Sleep Medicine, Level 2 West Hunter Medical Research Institute
Locked bag 1000
New Lambton Heights NSW 2305
Country 3514 0
Australia
Phone 3514 0
+61 2 4042 0143
Fax 3514 0
+61 2 4042 0046
Email 3514 0
peter.gibson@hnehealth.nsw.gov.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary