Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000967886
Ethics application status
Approved
Date submitted
14/06/2021
Date registered
23/07/2021
Date last updated
23/07/2021
Date data sharing statement initially provided
23/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Pragmatic Adaptive Trial for Respiratory Infections in Children (PATRIC) : Amoxicillin Duration
Scientific title
Pragmatic Adaptive Trial for Respiratory Infections in Children Platform: Amoxicillin Duration
Secondary ID [1] 304379 0
None
Universal Trial Number (UTN)
Trial acronym
PATRIC: Amoxicillin Duration
Linked study record
ACTRN12619000903189 - A Clinical Registry for Children presenting to Hospital with Respiratory Infections.
This record is a follow-up study of ACTRN12619000903189.

Health condition
Health condition(s) or problem(s) studied:
Acute Respiratory Infection 322169 0
Community Acquired Pneumonia 322170 0
Condition category
Condition code
Infection 319857 319857 0 0
Other infectious diseases
Respiratory 320281 320281 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Name: Amoxicillin (250mg/5mL)
Dose: 25mg/kg per dose, 3 times per day for participants up to 40kg
Duration: 2-5 days of therapy (Arms 1-4)
Arm 1 - 2 days of therapy
Arm 2 - 3 days of therapy
Arm 3 - 4 days of therapy
Arm 4 - 5 days of therapy (standard of care)
Mode: Oral syrup

Name: Amoxicillin 500mg capsule
Dose: 25mg/kg per dose, 3 times per day for participants over 40kg
Duration: 2-5 days of therapy (Arms 1-4)
Arm 1 - 2 days of therapy
Arm 2 - 3 days of therapy
Arm 3 - 4 days of therapy
Arm 4 - 5 days of therapy (standard of care)
Mode: Oral capsules

Intervention adherence to the randomised dose will be self-reported in follow-up electronic surveys.
Intervention code [1] 320819 0
Treatment: Drugs
Comparator / control treatment
5 days of Amoxicillin is the standard of care treatment arm.
The comparator treatment will be given via the same route of administration and at the same dose as the intervention.

Name: Amoxicillin (250mg/5mL)
Dose: 25mg/kg per dose, 3 times per day for participants up to 40kg
OR
Name: Amoxicillin 500mg capsule
Dose: 25mg/kg per dose, 3 times per day for participants over 40kg
Control group
Active

Outcomes
Primary outcome [1] 327848 0
The primary outcome is the proportion of children with symptom resolution (returning to pre-morbid health state, as assessed by parents/carers) assessed at 7 days following presentation. The outcome is assessed by parent report using a study specific electronic questionnaire on day 7 post-intervention commencement.
Timepoint [1] 327848 0
Day 7 post-intervention commencement.
Secondary outcome [1] 396769 0
Time to full recovery of ARI symptoms (measured in days, followed until day 28) for children in each treatment group.
The outcome is assessed using parent reported outcomes from electronic questionnaires on day 7, 14, 21 and 28 post-intervention commencement. The Canadian Acute Respiratory Illness and Flu Scale is used to assess symptom recovery.
Timepoint [1] 396769 0
Number of Days (until day 28).
The outcome is assessed in a parent reported electronic questionnaire each week (on day 7, 14, 21 and 28 post intervention commencement until the participant is recovered)
Secondary outcome [2] 396770 0
Time to seek further healthcare e.g. emergency department or general practice visit (measured in days, followed until day 28) for children in each treatment group.
This outcome will be assessed via parent report captured in a study specific electronic questionnaire on day 7, 14, 21, 28 post intervention commencement.
The medical record will also be checked for any participant who does not complete the electronic surveys or any participant who indicates they sought further healthcare since the last survey.
Timepoint [2] 396770 0
Number of days (until day 28).
This outcome will be assessed via parent report captured in in the electronic questionnaires on day 7, 14, 21, 28 post intervention commencement.
Secondary outcome [3] 396771 0
Proportion of children unable to comply with treatment allocation (measured as the proportion of total children in each treatment group whose treatment regime is modified by day 7).
This outcome will be assessed by parent reported study specific electronic questionnaire on day 7 post intervention commencement. The medical record will be checked for any participant who reports non-adherence to the treatment allocation on day 7.
Timepoint [3] 396771 0
Day 7 post-intervention commencement.
Secondary outcome [4] 396772 0
Time to return to normal childhood activities defined as: sufficient improvement to return to day-care; school; playgroups or other social outings (measured in days, followed until day 28) for children in each treatment group.
This outcome will be assessed with parent report a study specific electronic questionnaire completed on day 7, 14, 21 and 28 post-intervention commencement.
Timepoint [4] 396772 0
Number of days (until day 28).
Assessed on day 7, 14, 21 and 28 post-intervention commencement.
Secondary outcome [5] 396773 0
Proportion of children who have returned to their pre-morbid health state by day, 14, 21 and 28 (d14; d21; d28) for children in each treatment group as reported by parents a study specific electronic questionnaires.
Timepoint [5] 396773 0
Day 7, 14, 21 and 28 post-intervention commencement.
Secondary outcome [6] 396774 0
Proportion of children who are free from cough by day 7, 14, 21 and 28 (d7; d14; d21; d28) for children in each treatment group as assessed by parents in electronic questionnaires on day 7, 14, 21 and 28. The Canadian Acute Respiratory Illness and Flu Scale will be used to assess symptoms.
Timepoint [6] 396774 0
Day 7, 14, 21 and 28 post-intervention commencement.
Secondary outcome [7] 396775 0
Proportion of children who are free from fever by day 7, 14, 21 and 28 (d7; d14; d21; d28) for children in each treatment group.
This outcome will be assessed by parent report in electronic questionnaires. Parents will be asked if the temperature was measured with a thermometer and to record the measured temperature.
Timepoint [7] 396775 0
Day 7, 14, 21 and 28 post-intervention commencement.

Eligibility
Key inclusion criteria
1) Participants must be aged between greater than or equal to 6 months and 15 years.
2) Presence of fever and cough in the past 96 hours.
3) Total duration of symptoms <7 days at the time of enrolment.
4) Physician-diagnosed pneumonia; OR acute lower respiratory infection where antibiotics would be considered
Minimum age
6 Months
Maximum age
15 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Previous participation in PATRIC Clinical Registry or PATRIC Platform Trial within the last 12 months.
2) Parent/guardian has insufficient English proficiency to understand the study materials.
3) Parent/guardian is unwilling to provide consent.
4) Severe lower respiratory tract infection, identified by: i) the presence of hypoxia in room air (<90%); ii) the presence of WHO-defined danger signs (see definitions) or iii) requiring ICU admission.
5) Complicated LRTI, defined by either confirmation or clinical suspicion of: i) empyema; ii) infected para-pneumonic effusion or iii) lung abscess.
6) Patient displays severe respiratory distress (i.e. observations meet the Severe – Score 3 definitions; see PARROT chart).
7) Patient has bilateral auscultatory findings with a likely diagnosis of uncomplicated viral induced wheeze, bronchiolitis or asthma.
8) Patient is Intolerant to oral medications (refusal or vomiting).
9) Patient is currently receiving antibiotic therapy or taken antibiotics within the last 7 days.
10) Patient has known intolerance or allergy to amoxicillin or penicillin.
11) Parent and/or carer unable to return for medical review in the setting of clinical deterioration or lives outside the Perth metropolitan area.
12) Any concern that in the opinion of the responsible physician or investigator makes the potential participant unsuitable for the study.

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)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3 / Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
Intention to treat and per-protocol analyses will be implemented. Interim analyses will be based on intent to treat. Our primary analysis involves the estimation of a dose response curve using a dynamic linear model on the log-odds of response. While the primary analysis and decision model solely incorporates the randomised treatments, the model can be extended to include additional fixed or random effects.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
28/07/2021
Actual
Date of last participant enrolment
Anticipated
28/07/2023
Actual
Date of last data collection
Anticipated
25/08/2023
Actual
Sample size
Target
500
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 19733 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 34372 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 308750 0
Charities/Societies/Foundations
Name [1] 308750 0
Ramaciotti Foundation - Perpetual
Country [1] 308750 0
Australia
Funding source category [2] 308830 0
University
Name [2] 308830 0
University of Western Australia
Country [2] 308830 0
Australia
Primary sponsor type
Other
Name
Telethon Kids Institute
Address
Perth Children's Hospital, 15 Hospital Ave, Nedlands WA 6009.
Country
Australia
Secondary sponsor category [1] 309748 0
None
Name [1] 309748 0
Address [1] 309748 0
Country [1] 309748 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308668 0
Child and Adolscent Health Service Human Research Ethics Committee
Ethics committee address [1] 308668 0
Perth Children's Hospital
15 Hospital Avenue
Nedlands Western Australia 6009
Ethics committee country [1] 308668 0
Australia
Date submitted for ethics approval [1] 308668 0
17/02/2021
Approval date [1] 308668 0
29/03/2021
Ethics approval number [1] 308668 0
RGS4412

Summary
Brief summary
Acute respiratory infection (ARI) is a common cause of childhood morbidity and the most common reason for paediatric emergency department presentation and hospitalisation.
Despite numerous professional bodies describing the limited trial data available to inform management guidelines, there has been little progress towards evidence-based ARI care in developed nations in the past decade.
Antimicrobial use (or misuse) is a major driver for antimicrobial resistance (AMR) and identified by the WHO as an urgent threat to the prevention and treatment of an ever-increasing range of infections. AMR is a serious threat to global public health, requiring urgent action across all government sectors and society. Most antibiotics in children are prescribed for common paediatric conditions, particularly ARI. Our group has demonstrated that >50% of ARI-episodes are confirmed to be secondary to viral infections, yet >50% of children with fever and cough are prescribed antibiotics. Therefore, most antibiotics prescribed to children with ARI are likely to be unhelpful and given the impact on AMR, potentially harmful.
The primary objective of this trial is to generate the evidence for optimal duration of antibiotic treatment for pneumonia and ARIs in children. This trial will compare different treatment arms of amoxicillin for 2, 3, 4 or 5 days for physician-diagnosed pneumonia in children aged greater than or equal to 6 months to 15 years.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 111490 0
A/Prof Christopher Blyth
Address 111490 0
Perth Childrens Hospital
15 Hospital Ave
Nedlands, WA, 6009
Country 111490 0
Australia
Phone 111490 0
+61 8 6456 5614
Fax 111490 0
Email 111490 0
[email protected]
Contact person for public queries
Name 111491 0
Dr Rebecca Pavlos
Address 111491 0
Telethon Kids Institute, Perth Childrens Hospital
15 Hospital Ave
Nedlands, WA, 6009
Country 111491 0
Australia
Phone 111491 0
+61863191318
Fax 111491 0
Email 111491 0
[email protected]
Contact person for scientific queries
Name 111492 0
Dr Rebecca Pavlos
Address 111492 0
Telethon Kids Institute, Perth Childrens Hospital
15 Hospital Ave
Nedlands, WA, 6009
Country 111492 0
Australia
Phone 111492 0
+61 8 6319 1318
Fax 111492 0
Email 111492 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?

Current supporting documents:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
12045Study protocol  [email protected]


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
12045Study protocol  [email protected]

Results publications and other study-related documents

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

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIPragmatic Adaptive Trial for Respiratory Infection in Children (PATRIC) Clinical Registry protocol2024https://doi.org/10.1136/bmjopen-2023-074308
N.B. These documents automatically identified may not have been verified by the study sponsor.