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Trial registered on ANZCTR


Registration number
ACTRN12619000456156
Ethics application status
Approved
Date submitted
13/03/2019
Date registered
20/03/2019
Date last updated
27/02/2020
Date data sharing statement initially provided
20/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Preventing recurrent acute lower respiratory infections in young Indigenous children using long-term, once-weekly azithromycin: a multicentre randomised controlled trial
Scientific title
A multi-centre double-blind randomised controlled trial to determine if long-term once-weekly azithromycin (compared to placebo) reduces recurrent respiratory-related acute lower respiratory infections in young Indigenous children hospitalised with an acute lower respiratory infection
Secondary ID [1] 297621 0
Nil known
Universal Trial Number (UTN)
Trial acronym
PETAL Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute lower respiratory infection in children 311897 0
Condition category
Condition code
Respiratory 310482 310482 0 0
Other respiratory disorders / diseases
Infection 310633 310633 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will be randomised during hospital admission for an acute lower respiratory infection. Participants will then receive active or placebo treatment for 12 months.

Active arm: 12 months of oral azithromycin (200mg/5ml) formulation, given weekly (30mg/kg per dose)

Research staff or health centre staff will supervise weekly medication as above (oral suspension form) and complete medication diaries weekly. Empty medication bottles will be collected by the research team.
Intervention code [1] 313862 0
Treatment: Drugs
Comparator / control treatment
Placebo arm: 12 months of oral placebo (200mg/5ml) formulation, given weekly (30mg/kg per dose)

Both medications for the study are in suspension form and the placebo has been specifically commercially manufactured which as the same taste, appearance and smell as the azithromycin.
Control group
Placebo

Outcomes
Primary outcome [1] 319350 0
Rates of medically-treated acute lower respiratory infections (ALRI). We will capture ALRI through the child's medical records (community or hospital) and at clinical visits.
Timepoint [1] 319350 0
We aim to review these children at 12 months. Many children will reside in geographically isolated locations (in Australia), thus a range of 11-13 months is a reasonable time frame to capture ALRI data.
Secondary outcome [1] 367854 0
Rates of ALRI-hospitalisations
Timepoint [1] 367854 0
Data will be captured through medical chart reviews at 12 months
Secondary outcome [2] 367855 0
Serious adverse events (e.g. nausea, vomiting, diarrhoea, rash)
Timepoint [2] 367855 0
We will monitor adverse effects while children are actively taking the trial medication (until 12 months). Research staff will monitor adverse events weekly when supervising trial medication.
Secondary outcome [3] 367856 0
Nasopharyngeal respiratory bacterial pathogens and antibiotic resistance will be assessed using deep nasal swabs

This is a composite secondary outcome and can not be separated.
Timepoint [3] 367856 0
Nasopharyngeal respiratory bacterial pathogens and antibiotic resistance will be assessed using our research laboratory's previously published methods at baseline (admission to hospital), 12 (range 11-13 months) , 18 (17-19 months) and 24 months (range 23-25 months).
Secondary outcome [4] 367858 0
Cost-effective analysis
Timepoint [4] 367858 0
Data will be captured through chart reviews of children's medical records (e.g. hospital and community records) and respective electronic databases at 12 months
Secondary outcome [5] 368360 0
Chronic respiratory symptoms/signs of bronchiectasis at 24 months
Timepoint [5] 368360 0
Data will be captured through medical chart reviews at 24 months

Eligibility
Key inclusion criteria
1. Indigenous (Australian Aboriginal and/or Torres Strait Islander; or New Zealander Maori
and/or Pacific Islander)
2. Hospitalised with an ALRI (bronchiolitis or pneumonia)
3. Aged <2 years
4. Resident of site hospitals catchment areas and follow-up communities (NT only)
Minimum age
No limit
Maximum age
2 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known chronic lung disease (e.g. cystic fibrosis, bronchiectasis)
2. Already receiving regular azithromycin (within the last 4 weeks)
3. Contraindication for macrolide use (e.g. liver dysfunction, hypersensitivity)
4. Primary carer lacks a mobile phone for follow-up; or
5. Unable to attend follow up clinical visits over the next 24 months

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)
Sequential allocation list with each next position concealed by sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block design (4-6 block size)
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 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis
An intention to treat approach will be used and per protocol for sensitivity analysis.

Primary aim: The main effects of the interventions will be determined by comparing the primary outcome. Rates of medically-treated acute lower respiratory infections (ALRI) at 12 months.The main effect of the intervention will be determined using negative binomial regression (expressed as IRR, 95%CI). A-priori sub-analyses will report outcomes by age (less than or equal to 12 months, greater than 12 months) and adherence (less than or equal to 70% or greater than 70%).

Secondary aims: Rates of ALRI-hospitalisations at 12 months will be compared between treatment groups using negative binomial regression (expressed as IRR, 95%CI). Children with bronchiectasis at 24 months will be compared using proportions. Adverse events will be compared between treatment groups using a Chi2 test (expressed as OR, 95%CI). Longitudinal logistic regression will be used to determine the difference between treatment groups for respiratory bacterial pathogens and antimicrobial resistance. Cost-effectiveness will be analysed using incremental cost-effectiveness ratios using the Bootstrap method for inference.

Recruitment
Recruitment status
Not yet 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
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NT
Recruitment hospital [1] 13315 0
Royal Darwin Hospital - Tiwi
Recruitment postcode(s) [1] 25915 0
0810 - Tiwi
Recruitment outside Australia
Country [1] 21331 0
New Zealand
State/province [1] 21331 0
Auckland

Funding & Sponsors
Funding source category [1] 302163 0
Government body
Name [1] 302163 0
National Health and Medical Research Council
Address [1] 302163 0
GPO Box 1421
Canberra City ACT 2601
Country [1] 302163 0
Australia
Primary sponsor type
Other
Name
Menzies School of Health Research
Address
PO Box 41096
Casuarina NT 0811
Country
Australia
Secondary sponsor category [1] 302001 0
None
Name [1] 302001 0
N/A
Address [1] 302001 0
N/A
Country [1] 302001 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302844 0
Human Research Committee of the Northern Territory Department of Health and Menzies School of Health Research
Ethics committee address [1] 302844 0
PO Box 41096
Casuarina NT 0811
Ethics committee country [1] 302844 0
Australia
Date submitted for ethics approval [1] 302844 0
03/04/2019
Approval date [1] 302844 0
Ethics approval number [1] 302844 0
Ethics committee name [2] 302845 0
Health and Disability Ethics Committee
Ethics committee address [2] 302845 0
Ministry of Health
PO Box 5013
Wellington NZ 6011
Ethics committee country [2] 302845 0
New Zealand
Date submitted for ethics approval [2] 302845 0
01/05/2019
Approval date [2] 302845 0
18/07/2019
Ethics approval number [2] 302845 0

Summary
Brief summary
Early and repeated acute lower respiratory infections (ALRI) in young children increase the risk for chronic lung diseases, such as bronchiectasis which is highly prevalent among Indigenous populations. Our hypothesis is that Indigenous children receiving long-term azithromycin will have fewer medically-treated episode of ALRI within the first 12 months.
Trial website
Trial related presentations / publications
Public notes
Nasopharyngeal, oropharngeal and faecal samples are being collected at baseline, 12, 18 and 24 months and will be stored for future upper airway and gut microbiota analysis when funding becomes available.

Contacts
Principal investigator
Name 91586 0
Dr Gabrielle McCallum
Address 91586 0
Menzies School of Health Research
PO Box 41096
Casuarina NT 0811
Country 91586 0
Australia
Phone 91586 0
+61889468565
Fax 91586 0
Email 91586 0
gabrielle.mccallum@menzies.edu.au
Contact person for public queries
Name 91587 0
Dr Gabrielle McCallum
Address 91587 0
Menzies School of Health Research
PO Box 41096
Casuarina NT 0811
Country 91587 0
Australia
Phone 91587 0
+61889468565
Fax 91587 0
Email 91587 0
gabrielle.mccallum@menzies.edu.au
Contact person for scientific queries
Name 91588 0
Dr Gabrielle McCallum
Address 91588 0
Menzies School of Health Research
PO Box 41096
Casuarina NT 0811
Country 91588 0
Australia
Phone 91588 0
+61889468565
Fax 91588 0
Email 91588 0
gabrielle.mccallum@menzies.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Due to cultural considerations for our participant group, it is not currently planned to have data available for public access.
What supporting documents are/will be available?
Other
'Other' documents specified
We will publish our study protocol.
How or where can supporting documents be obtained?
Type [1] 7147 0
Other
Citation [1] 7147 0
Link [1] 7147 0
Email [1] 7147 0
gabrielle.mccallum@menzies.edu.au
Other [1] 7147 0
Ethics reference number: HREC-19-3401
Attachment [1] 7147 0
Summary results
No Results