Impact of Clinical Guidance & Point-of-care CRP in Children: the ARON Project

NCT ID: NCT04470518

Last Updated: 2025-04-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 6750 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-06
• Study Completion Date: 2024-04-24

Brief Summary

Impact of clinical guidance & point-of-care CRP test in children: the ARON project Trial Design: multicentre, cluster-randomized, parallel group pragmatic trial Trial Participants and setting: Children aged 6 months to 12 years of age with an acute illness episode presenting to in-hours general practice or out-of-hospital community paediatrics offices

Intervention(s) Diagnostic algorithm:

1. Clinical decision tree: clinician's gut feeling something is wrong, dyspnea, temperature ≥40ºC

2. YES to any : point-of-care CRP ≥5mg/L: additional testing or refer to secondary care <5mg/L: safety netting*, only prescribe antibiotics if advised (guidelines)

3. NO to all : are AB considered? YES : point-of-care CRP ≥5mg/L: safety netting*, only prescribe antibiotics if advised (guidelines) <5mg/L: safety netting*, do not prescribe antibiotics NO: safety netting

*safety netting advice:

• inform parents on what to expect and what to look out for
• interactive parent information booklet based on previous research

Control: Diagnosis and Treatment/Management as per usual care:

• guidance on AB prescribing:

o Belgische Commissie voor de Coördinatie van het Antibioticabeleid (BAPCOC) guide (updated November 2019)

o RIZIV consensus meeting report "Antibiotics in children in ambulatory care"

Primary Endpoint: Antibiotic prescribing rate at index consultation

Secondary Endpoint(s)

• time until full clinical recovery (during follow up (day 1 to day 30))

• additional investigations (at index consultation and/or during follow up (day 1 to day 30))

• re-consultation (during follow up (day 1 to day 30))

• antibiotic prescribing rate (during follow up (day 1 to day 30))

Exploratory endpoints at the index consultation:

• additional investigations (X-Ray, blood tests, urine tests, etc.)

During a follow-up period (day 1 to day 30):

• referral to hospital

• additional investigations (X-Ray, blood tests, urine tests, etc.)
• patients with full clinical recovery at day 7 and day 30
• admission to hospital
• mortality
• cost-effectiveness
• patient satisfaction
• qualitative study: endpoints

Planned Sample Size: 7000 Timing of the intervention: Intervention at index consultation (at presentation to primary care) Follow-up duration: 30 days follow-up Duration of the trial (FPI-CSR): 43 months

Detailed Description

The investigators aim to strengthen the assessment of acutely ill children in primary care, by introducing a diagnostic algorithm that can decrease antibiotic prescribing.

In light of the prior evidence and its results so far, the ARON trial will test the impact of a diagnostic algorithm including a standardised clinical assessment, a POC CRP test, and safety netting advice.

Therefore, the investigators propose to assess the clinical and cost-effectiveness of a diagnostic algorithm which includes a decision tree, POC CRP and safety netting advice in acutely ill children aged 6 months to 12 years of age presenting to ambulatory care, on AB prescribing, referral/admission to hospital, additional testing, mortality, and patient satisfaction.

More specifically, the investigators' research question is whether this diagnostic algorithm is able to safely reduce antibiotic prescribing in acutely ill children presenting to ambulatory care.

The decision whether or not to conduct a POC CRP test will depend on the standardized clinical assessment, i.e. a validated clinical decision tree, and subsequently for low-risk children on the intention to prescribe AB.

The investigators will provide clear evidence-based guidance on how to interpret the CRP test result as outlined below.

A process evaluation will examine how clinicians use CRP testing in their practice and how parents experience these consultations.

The investigators propose a study, where children (6 months to 12 years of age) will be randomised to (a) a diagnostic algorithm with CRP testing and specific guidance on when to prescribe AB or (b) usual care. CRP testing will be done using a finger prick test (result within 4 minutes). The CRP level will then be given to the clinician who will communicate the result to the child/parents.

The investigators aim to recruit 7000 children and will collect data registered by the participating physician, from the child's health record and children/parents directly. The investigators will describe how the intervention has worked in practice and how clinicians/parents have experienced these consultations.

Guidance will be part of a diagnostic algorithm which includes clinically guided POC CRP testing and safety netting advice to inform parents on what to expect and what to look out for.

Individual interviews will be conducted with clinicians and parents taking part in the trial within 30 days after the first contact consultation, to explore the social processes influencing embedding of the intervention within practice, and behaviour change techniques.

These individual telephone interviews will be performed with a selection of parents to address whether their concerns were discussed appropriately and whether their expectations were met and how they experienced the consultation and/or POC CRP testing.

The safety-netting advice will be supported by a parent information booklet, based on previous research (the "When should I worry"-interactive booklet (a guide to Coughs, Colds, Earache & Sore Throats), the "Mijn kind heeft koorts" booklet (Eefje de Bont, www.thuisarts.nl), and the "Caring for children with coughs"-leaflet (information about how to look after a child who has a cough and when to see the doctor)).

The findings of this study could change the practice of ambulatory care physicians and might be of great interest to parents and childcare providers. The investigators will publish the findings of this research in academic journals, present at national conferences and discuss results with groups responsible for the national guidance on how to assess acutely ill children (Domus Medica, SSMG).

Conditions

Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Intervention: Diagnostic algorithm

diagnostic algorithm including a standardised clinical assessment, a Point-of-care C-reactive protein test, and safety netting advice

Group Type: ACTIVE_COMPARATOR

diagnostic algorithm

Intervention Type: OTHER

Guidance will be part of a diagnostic algorithm which includes clinically guided point-of-care C-reactive protein testing and safety netting advice to inform parents on what to expect and what to look out for. A selection of clinical features will be assessed and recorded by the physician in the patient's health record and on the e-CRF, including the clinical decision tree (clinician's gut feeling, body temperature, dyspnea).

The safety-netting advice will be supported by a parent information booklet, based on previous research (the "When should I worry"-interactive booklet (a guide to Coughs, Colds, Earache & Sore Throats), the "Mijn kind heeft koorts" booklet (Eefje de Bont, www.thuisarts.nl), and the "Caring for children with coughs"-leaflet (information about how to look after a child who has a cough and when to see the doctor)).

Usual care

In the control arm, patients will receive 'usual care' left at the discretion of the treating physician.

Apart from the general training session for all participating physicians they have attended prior to recruitment and randomization, physicians in the control arm will not receive additional tools.

They are expected (but not forced) to follow the Belgian guidelines (as described in "BAPCOC National guidelines and the RIZIV consensus meeting "Rational use of antibiotics in children").

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

diagnostic algorithm

Guidance will be part of a diagnostic algorithm which includes clinically guided point-of-care C-reactive protein testing and safety netting advice to inform parents on what to expect and what to look out for. A selection of clinical features will be assessed and recorded by the physician in the patient's health record and on the e-CRF, including the clinical decision tree (clinician's gut feeling, body temperature, dyspnea).

The safety-netting advice will be supported by a parent information booklet, based on previous research (the "When should I worry"-interactive booklet (a guide to Coughs, Colds, Earache & Sore Throats), the "Mijn kind heeft koorts" booklet (Eefje de Bont, www.thuisarts.nl), and the "Caring for children with coughs"-leaflet (information about how to look after a child who has a cough and when to see the doctor)).

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Being able to recruit acutely ill children (ideally consecutively)
• Agree to the terms of the clinical study agreement.

• Children aged 6 months to 12 years, provided informed consent can be obtained
• presenting with an acute illness episode that started maximum 10 days before the index consultation

Exclusion Criteria

• Currently using a POC CRP device as part of their routine care
• No practices will be excluded on other grounds than the above. Age, demographics, geographic region will not be used to exclude eligible practices. This will provide us with a real-life, representative subset of ambulatory care physicians.

• Children who were previously included in this trial
• children with an underlying known chronic condition (e.g. asthma, immune deficiency)
• clinically unstable warranting immediate care
• immunosuppressant medication taken in the previous 30 days
• trauma as the main presenting problem
• antibiotics taken in the previous 7 days
• Unwillingness or inability to provide informed consent

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: collaborator

University Ghent

OTHER

Sponsor Role: collaborator

Universiteit Antwerpen

OTHER

Sponsor Role: collaborator

University of Liege

OTHER

Sponsor Role: collaborator

Vrije Universiteit Brussel

OTHER

Sponsor Role: collaborator

Université Catholique de Louvain

OTHER

Sponsor Role: collaborator

KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Jan Verbakel

Professor Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jan Y Verbakel, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

KU Leuven

Locations

GPs associated with KU Leuven

Leuven, , Belgium

Countries

Belgium

References

Verbakel JY, Lemiengre MB, De Burghgraeve T, De Sutter A, Aertgeerts B, Bullens DMA, Shinkins B, Van den Bruel A, Buntinx F. Point-of-care C reactive protein to identify serious infection in acutely ill children presenting to hospital: prospective cohort study. Arch Dis Child. 2018 May;103(5):420-426. doi: 10.1136/archdischild-2016-312384. Epub 2017 Dec 21.

Reference Type: BACKGROUND

PMID: 29269559 (View on PubMed)

Verbakel JY, Aertgeerts B, Lemiengre M, Sutter AD, Bullens DM, Buntinx F. Analytical accuracy and user-friendliness of the Afinion point-of-care CRP test. J Clin Pathol. 2014 Jan;67(1):83-6. doi: 10.1136/jclinpath-2013-201654. Epub 2013 Sep 11. No abstract available.

Reference Type: BACKGROUND

PMID: 24025452 (View on PubMed)

Verbakel JY, Lemiengre MB, De Burghgraeve T, De Sutter A, Aertgeerts B, Shinkins B, Perera R, Mant D, Van den Bruel A, Buntinx F. Should all acutely ill children in primary care be tested with point-of-care CRP: a cluster randomised trial. BMC Med. 2016 Oct 6;14(1):131. doi: 10.1186/s12916-016-0679-2.

Reference Type: BACKGROUND

PMID: 27716201 (View on PubMed)

Verbakel JY, Burvenich R, D'hulster E, De Rop L, Van den Bruel A, Anthierens S, Coenen S, De Sutter A, Heytens S, Joly L, Digregorio M, Laenen A, Luyten J, De Burghgraeve T. A clinical decision tool including a decision tree, point-of-care testing of CRP, and safety-netting advice to guide antibiotic prescribing in acutely ill children in primary care in Belgium (ARON): a pragmatic, cluster-randomised, controlled trial. Lancet. 2025 Oct 11;406(10512):1599-1610. doi: 10.1016/S0140-6736(25)01239-5. Epub 2025 Sep 25.

Reference Type: DERIVED

PMID: 41016406 (View on PubMed)

Verbakel JYJ, De Burghgraeve T, Van den Bruel A, Coenen S, Anthierens S, Joly L, Laenen A, Luyten J, De Sutter A. Antibiotic prescribing rate after optimal near-patient C-reactive protein testing in acutely ill children presenting to ambulatory care (ARON project): protocol for a cluster-randomized pragmatic trial. BMJ Open. 2022 Jan 3;12(1):e058912. doi: 10.1136/bmjopen-2021-058912.

Reference Type: DERIVED

PMID: 34980633 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

S62005

Identifier Type: -

Identifier Source: org_study_id