Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001486819
Ethics application status
Approved
Date submitted
18/09/2021
Date registered
1/11/2021
Date last updated
18/10/2022
Date data sharing statement initially provided
1/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of prophylactic azithromycin on chest infections in children with neurological and neuromuscular impairment
Scientific title
Randomised, triple blinded, placebo trial comparing 26 weeks of azithromycin to placebo in children with neurological/neuromuscular impairment to reduce the the risk of lower respiratory tract infection
Secondary ID [1] 305337 0
None
Universal Trial Number (UTN)
Trial acronym
PARROT-Junior
Linked study record
ACTRN12619001597189 which is a parent study. PARROT-Junior is a sub-study of Parrot.

Health condition
Health condition(s) or problem(s) studied:
Neurological impairment 323658 0
Lower respiratory tract infection 323659 0
Condition category
Condition code
Respiratory 321196 321196 0 0
Other respiratory disorders / diseases
Neurological 321203 321203 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Azithromycin

The dosing regimen is based on body weight (10mg/kg rounded) and will be administered as an oral suspension 3 times weekly (Mon/Wed/Fri) for 26 weeks.

Adherence to the trial medications will be monitored using a treatment diary and withdrawals from study treatment will also be monitored.
Intervention code [1] 321747 0
Treatment: Drugs
Comparator / control treatment
Placebo

Placebo matching azithromycin will be supplied as powder for oral suspension. Inert, matched excipients are used.
Control group
Placebo

Outcomes
Primary outcome [1] 328990 0
Rate of (Lower Respiratory Tract Infection) LRTIs measured in child-months assessed by both parent self-report and medical reports.
Timepoint [1] 328990 0
6 months from commencement of trial medications given
Secondary outcome [1] 401044 0
Proportion of children with LRTI over the 26-weeks intervention period, assessed by both parent self-report and medical reports.
Timepoint [1] 401044 0
6 months from time trial medications commenced
Secondary outcome [2] 401045 0
Adverse events assessed by both parent self-report (on diaries) and medical reports. These include but are not restricted to mild diarrhoea, abdominal pains, nausea or vomiting, headache and dizziness.
Timepoint [2] 401045 0
During the 6 months of the intervention period
Secondary outcome [3] 401046 0
Quality-adjusted life years (QALY) assessment (composite outcome).

CHU9D and EQ-5D-Y are used to evaluate the outcome measure for QALY. However, as not all the questions are applicable for the young children i.e. only applicable questions (for age) will be used.
Timepoint [3] 401046 0
Baseline and at 6 months from commencement of trial medications
Secondary outcome [4] 401064 0
Change in health related QoL of parent/carer using Parent QoL assessment (Warwick-Edinburgh)
Timepoint [4] 401064 0
Baseline and at 6 months from commencement of trial medications
Secondary outcome [5] 401065 0
Respiratory symptom questionnaire
Timepoint [5] 401065 0
Baseline and at 6 months from commencement of trial medications

Eligibility
Key inclusion criteria
1. Children and young people who are aged between 0.5-3 years (inclusive) at randomisation
2. Written informed consent from legal guardian
3. Diagnosed with non-progressive neurological impairment (includes stable neuromuscular abnormalities), AND
4. One or more of the following:
a) Received at least 2 courses of oral antibiotics for LRTI in 26 weeks prior to eligibility
b) Have been hospitalised with a LRTI within 52 weeks prior to eligibility and completed
c) Prescribed prophylactic antibiotics for LRTIs and undergone a 4 week ‘washout’ period'.
Minimum age
6 Months
Maximum age
3 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Progressive neuromuscular disorders such as Duchenne muscular dystrophy etc., or neurological disorders in which progressive deterioration in neurological condition are known to occur (e.g. Rett syndrome, some neurometabolic syndromes)
2. Pre-existing non-neurological conditions that impact on respiratory function such as cystic fibrosis (CF), immunodeficiency etc. Children with neurological impairment known to have bronchiectasis will not be excluded.
3. Known contra-indication to using (e.g. prolonged QT syndrome) or hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide antibiotic or to any of the excipients contained in the study drug
4. Use of macrolide antibiotics within 90 days prior to eligibility
5. Known significant hepatic disease (hepatic impairment per Child-Pugh classification C)
6. Treatment with ergot derivatives (dihydroergocristine, dihydroergotamine, dihydroergotoxine, nicergoline or a combination of dihydroergocryptine with caffeine)
OR
7. Recruited to another investigation medical product (IMP) trial and continuing to administer the IMP.

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)
Triple blinded trial so the parent/child, research/treating clinical team and statistical analysis will be blinded to treatment allocation. There will be a designated unblinding team (usually pharmacy) at each centre who will be unblinded to treatment allocations. Randomisation will occur via a randomisation system and there will be back-up randomisation envelopes. Only the unblinded team will receive information regarding the unblinded treatment allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation lists will be generated using block randomisation with random variable block length, stratified by site.
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 / Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
To detect a 50% reduction in rate of LRTIs, with 80% power (alpha 0.05), we would require 40 patients per group, increasing to 94 allowing for 15% loss to follow-up/attrition, i.e. 94 children in total. We will compare the primary outcomes between groups using incident rate ratios with 95%CI presented.

Data of the first 6 months of intervention from children recruited from Brisbane and Darwin-based sites from the parent PARROT study will be included in this study and counted as part of the required total sample size. A sensitivity analysis will be undertaken to include only these younger children.

A Statistical Analysis Plan (SAP) will be developed prior to the final analyses of the trial.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
10/11/2021
Actual
15/12/2021
Date of last participant enrolment
Anticipated
31/12/2023
Actual
Date of last data collection
Anticipated
31/12/2024
Actual
Sample size
Target
94
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
NT,QLD
Recruitment hospital [1] 20542 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [2] 20543 0
Royal Darwin Hospital - Tiwi
Recruitment postcode(s) [1] 35324 0
4101 - South Brisbane
Recruitment postcode(s) [2] 35832 0
0810 - Casuarina

Funding & Sponsors
Funding source category [1] 309706 0
University
Name [1] 309706 0
Queensland University of Technology
Country [1] 309706 0
Australia
Funding source category [2] 309881 0
University
Name [2] 309881 0
Menzies School of Health Research
Country [2] 309881 0
Australia
Primary sponsor type
University
Name
Menzies School of Health Research
Address
John Mathews Building (Building 58)
Royal Darwin Hospital Campus
Rocklands Drive
Casuarina NT 0810
Country
Australia
Secondary sponsor category [1] 310729 0
University
Name [1] 310729 0
Queensland University of Technology
Address [1] 310729 0
Centre for Children’s Health Research
62 Graham Street
South Brisbane QLD 4101
Country [1] 310729 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309469 0
Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee
Ethics committee address [1] 309469 0
Level 7, Centre for Children’s Health Research Queensland Children’s Hospital Precinct 62 Graham Street, South Brisbane QLD 4101
Ethics committee country [1] 309469 0
Australia
Date submitted for ethics approval [1] 309469 0
30/09/2021
Approval date [1] 309469 0
01/12/2021
Ethics approval number [1] 309469 0
HREC/21/QCHQ/80216
Ethics committee name [2] 309473 0
Human Research Committee of the Northern Territory Dept of Health and Menzies School of Health Research
Ethics committee address [2] 309473 0
John Mathews Building (Building 58)
Royal Darwin Hospital Campus
Rocklands Drive
Casuarina NT 0810
Ethics committee country [2] 309473 0
Australia
Date submitted for ethics approval [2] 309473 0
30/09/2021
Approval date [2] 309473 0
Ethics approval number [2] 309473 0

Summary
Brief summary
Neurological Impairment (NI) in children is often caused by conditions such as cerebral palsy and other neuromuscular conditions. Many children with NI are prone to chest infections which can lead to long stays in hospital, additional impairment and even premature death. Despite the suffering caused to children and their families by these infections and the high cost to health services, there is very little information on how best to prevent them. Some doctors prescribe long-term antibiotics but we don't really know whether this treatment makes any difference to the numbers of chest infections children suffer from, or whether these antibiotics can cause long term harm.

The trial (PARROT-Junior) is a sub-study of a parent study (PARROT). In PARROT-Junior, we will recruit children aged 0.3-3 years, with NI who are at risk of chest infections, along with their parents/primary care giver to take part. Children included in the trial will be given either azithromycin or a placebo for 6 months to evaluate whether regular azithromycin reduces the frequency of chest infections.

For the analysis, results from PARROT-Junior will be combined with data from the children recruited from Brisbane/Darwin in the parent study (PARROT). Our target sample size thus includes the subset of Brisbane/Darwin-enrolled children from PARROT.
Trial website
Trial related presentations / publications
Public notes
The total sample size of 94 includes the subset of Brisbane/Darwin-enrolled children from the parent PARROT study.

Contacts
Principal investigator
Name 114258 0
Prof Anne Chang
Address 114258 0
Level 7, Centre for Children’s Health Research Queensland Children’s Hospital Precinct 62 Graham Street, South Brisbane QLD 4101
Country 114258 0
Australia
Phone 114258 0
+61 730697283
Fax 114258 0
Email 114258 0
[email protected]
Contact person for public queries
Name 114259 0
Mrs Anne Cook
Address 114259 0
Level 7, Centre for Children’s Health Research Queensland Children’s Hospital Precinct 62 Graham Street, South Brisbane QLD 4101
Country 114259 0
Australia
Phone 114259 0
+61 730697283
Fax 114259 0
Email 114259 0
[email protected]
Contact person for scientific queries
Name 114260 0
Prof Anne Chang
Address 114260 0
Level 7, Centre for Children’s Health Research Queensland Children’s Hospital Precinct 62 Graham Street, South Brisbane QLD 4101
Country 114260 0
Australia
Phone 114260 0
+61 730681111
Fax 114260 0
Email 114260 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
The NT based ethics committee has deemed that sharing of patient level data is not permissible unless specific consent has been obtained for all of our trials.


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.