Trial Review

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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
30/01/2025
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 First Nations and Timorese 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 First Nations and Timorese 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 maximum 12 months, with a opt out option for children at 6 months.

Active arm: 6-12 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.
Intervention code [1] 313862 0
Treatment: Drugs
Comparator / control treatment
All participants will be randomised during hospital admission for an acute lower respiratory infection. Participants will then receive active or placebo treatment for maximum 12 months, with a opt out option for children at 6 months.

Placebo arm: 6-12 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 6-months for those who received 6 months of study trial medication and 12 months for those who received 12 months. Many children will reside in geographically isolated locations (in Australia), thus a range of 5-7 months (6 month treatment) or 11-13 months (12 month treatment) is a reasonable time frame to capture ALRI data.
Secondary outcome [1] 367854 0
Rate and proportion of ALRI-hospitalisations within the intervention period at 6-12 months
Timepoint [1] 367854 0
Data will be captured through medical chart reviews at 6-12 months
Secondary outcome [2] 367855 0
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, unless families choose to opt out of receiving trial medication at 6 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). For families choosing to opt out of receiving trial medication at 6 months nasopharyngeal respiratory bacterial pathogens and antibiotic resistance will be assessed at 6 (range 6-8 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 6-12 months
Secondary outcome [5] 368360 0
Chronic respiratory symptoms/signs suggestive of underlying CSLD or bronchiectasis at 24-months
Timepoint [5] 368360 0
Data will be captured through medical chart reviews at 24 months
Secondary outcome [6] 444439 0
ALRI-hospitalisations during and post-intervention will be determined by review of participants medical records.
Timepoint [6] 444439 0
At 24-months post-commencement of trial medications

Eligibility
Key inclusion criteria
(1) First Nations (Australian Aboriginal and/or Torres Strait Islander; or NZ Maori and/or Pacific Islander; or Timorese)
(2) Hospitalised with an ALRI (bronchiolitis or pneumonia) and resident of site hospitals catchment areas
(2) Aged <2 years
(3) Required oxygen or respiratory support at any point of current illness (including transfer and in the community) OR fluid support (NG or IV) OR have had recurrent ALRI-related admission within previous 3 months.

In addition, New Zealand children are to be aged greater than or equal to 3 months, a condition required by the local human research ethics committee.
Minimum age
No limit
Maximum age
2 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(1) Known chronic lung disease (e.g. cystic fibrosis, radiographic-confirmed bronchiectasis, chronic neonatal lung disease)
(2) Receiving regular azithromycin (within the last 4 weeks)
(3) Macrolide contraindicated (e.g. known liver dysfunction, hypersensitivity)
(4) Primary carer lacks a mobile phone and/or is unable to attend follow-up clinical visits over the next 24-months
(5) participation in another respiratory-related randomised controlled trial

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. Missing data will not be imputed. No interim analysis is planned. Any post-hoc analysis or unplanned analyses will be described clearly.

Primary aim: The main effects of the intervention will be determined by the rate of medically-treated ALRIs whilst receiving the intervention. Those randomised to receive 6-12 months of azithromycin will be compared to with those receiving placebo (controls). We will use a negative binomial regression model and report IRR 95%CI, including treatment group and the number of months taking treatment in the study included as an offset will be used to determine between-group differences with 95%CIs. Subgroup-analyses will be done for age (=12, >12 months) and adherence (= or >70%).

Secondary aims: The rate and proportion of children with ALRI-hospitalisations within the intervention period at 6-12 months will be compared using negative binomial regression (reporting IRR, 95% confidence intervals [CI]) whilst on the intervention. Adverse events will be compared between treatment groups using risk differences (95%CI) whilst on the intervention. The proportion of children with symptoms/signs of bronchiectasis at 24 months will be used between treatment groups. 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
Recruiting
Date of first participant enrolment
Anticipated
30/03/2020
Actual
20/10/2020
Date of last participant enrolment
Anticipated
31/01/2025
Actual
Date of last data collection
Anticipated
31/01/2027
Actual
Sample size
Target
160
Accrual to date
158
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
Country [2] 25093 0
Timor-Leste
State/province [2] 25093 0
Dili

Funding & Sponsors
Funding source category [1] 302163 0
Government body
Name [1] 302163 0
National Health and Medical Research Council
Country [1] 302163 0
Australia
Primary sponsor type
Other
Name
Menzies School of Health Research
Country
Australia
Secondary sponsor category [1] 302001 0
None
Name [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
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
HREC 2019-3401
Ethics committee name [2] 302845 0
Health and Disability Ethics Committee
Ethics committee address [2] 302845 0
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
19/STH/108
Ethics committee name [3] 311887 0
Institue National of Health Research and Technical committee
Ethics committee address [3] 311887 0
Ethics committee country [3] 311887 0
Timor-Leste
Date submitted for ethics approval [3] 311887 0
27/05/2022
Approval date [3] 311887 0
27/09/2022
Ethics approval number [3] 311887 0
1901 MS-INS/GDE/IX/2022

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 91586 0
A/Prof 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
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
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 the study consider sharing individual participant data?
No
No IPD sharing reason/comment: There are no plans to grant public access to the full protocol, participant-level dataset or statistical code due to cultural considerations such as including respect for privacy, sensitivity to local norms/traditions, and potential implications for community relations.



What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Other  gabrielle.mccallum@menzies.edu.au Ethics reference number: HREC-19-3401


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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