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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

30/07/2024

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]

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

Community Acquired Pneumonia

Condition category

Condition code

Infection

Other infectious diseases

Respiratory

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]

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]

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]

Day 7 post-intervention commencement.

Secondary outcome [1]

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]

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]

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]

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]

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]

Day 7 post-intervention commencement.

Secondary outcome [4]

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]

Number of days (until day 28).
Assessed on day 7, 14, 21 and 28 post-intervention commencement.

Secondary outcome [5]

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]

Day 7, 14, 21 and 28 post-intervention commencement.

Secondary outcome [6]

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]

Day 7, 14, 21 and 28 post-intervention commencement.

Secondary outcome [7]

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]

Day 7, 14, 21 and 28 post-intervention commencement.

Secondary outcome [8]

Proportion of children who 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 [8]

Secondary outcome [9]

Timepoint [9]

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.

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 <21 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?

Key exclusion criteria

1) Previous participation in PATRIC Clinical Registry or PATRIC Platform Trial within the last 3 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:
a.) the presence of hypoxia in room air (<90%)
b.) the presence of WHO-defined danger signs (see definitions)
c.) if sepsis is suspected OR
d.) requiring ICU admission
5) Complicated LRTI, defined by either confirmation or clinical suspicion of:
a.) empyema
b.) infected para-pneumonic effusion OR
c.) 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

Recruiting

Date of first participant enrolment

Anticipated

1/02/2022

Actual

26/02/2022

Date of last participant enrolment

Anticipated

18/02/2025

Actual

Date of last data collection

Anticipated

18/03/2025

Actual

Sample size

Target

500

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Perth Children's Hospital - Nedlands

Recruitment postcode(s) [1]

6009 - Nedlands

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Ramaciotti Foundation - Perpetual

Address [1]

GPO Box 4171, Sydney NSW 2001

Country [1]

Australia

Funding source category [2]

University

Name [2]

University of Western Australia

Address [2]

35 Stirling Hwy, Crawley WA 6009

Country [2]

Australia

Funding source category [3]

Charities/Societies/Foundations

Name [3]

PCH Foundation

Address [3]

Country [3]

Australia

Funding source category [4]

Government body

Name [4]

NHMRC Investigator Grant

Address [4]

Country [4]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Child and Adolscent Health Service Human Research Ethics Committee

Ethics committee address [1]

Perth Children's Hospital
15 Hospital Avenue
Nedlands Western Australia 6009

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

17/02/2021

Approval date [1]

29/03/2021

Ethics approval number [1]

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

Prof Christopher Blyth

Address

Perth Childrens Hospital
15 Hospital Ave
Nedlands, WA, 6009

Country

Australia

Phone

+61 8 6456 5614

Fax

[email protected]

Contact person for public queries

Name

Erin van der Helder

Address

Telethon Kids Institute, Perth Childrens Hospital
15 Hospital Ave
Nedlands, WA, 6009

Country

Australia

Phone

+61 8 6456 8701

Fax

[email protected]

Contact person for scientific queries

Name

Erin van der Helder

Address

Telethon Kids Institute, Perth Childrens Hospital
15 Hospital Ave
Nedlands, WA, 6009

Country

Australia

Phone

+61 8 6456 8701

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
12045	Study protocol			[email protected]

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Dimensions AI	Pragmatic Adaptive Trial for Respiratory Infection in Children (PATRIC) Clinical Registry protocol	2024	https://doi.org/10.1136/bmjopen-2023-074308

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically