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

NCT04470518 | Completed Results DMC

• 1 other identifier: S62005
• Study Type: interventional
• Target: 6,750
• Locations: 1 country
• Sites: 1

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:

• 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

Conditions

Infection

Keywords

antibiotic prescription; infections; decision tree; point-of-care C-reactive protein test; safetynet advice

Outcome Measures

Primary Outcomes (1)

• Antibiotic Prescribing Rate at Index Consultation (Immediate or Delayed)

  The primary outcome is the percentage of participants who were prescribed antibiotic treatment (both immediate and delayed) at the index consultation as recorded by the treating physician.

  This outcome will be registered immediately at the index consultation (immediately after the intervention)

Secondary Outcomes (4)

• Clinical Recovery During Follow-up

  This outcome will be checked from the diary (via app for parents) from first day after the intervention until day of full clinical recovery (up to maximum 30 days after after the intervention)

• Additional Investigations at Index Consultation and/or During Follow-up

  This composite outcome will be registered immediately after the intervention and/or checked from the patient health record from the first day to day 30 after the intervention

• Re-consultation During Follow-up

  This outcome will be checked from the patient health record from first day to day 30 after the intervention

• Antibiotic Prescribing Rate During Follow-up

  This outcome will be checked from the patient health record first day to day 30 after the intervention

Other Outcomes (15)

• Additional Testing at Index Consultation

  This outcome will be registered immediately at the index consultation

• Additional Testing During Follow-up

  during follow-up from first day to day 30 after the intervention

• Referral to Hospital at Day 0

  This outcome will be registered immediately at the index consultation

Study Arms (2)

Intervention: Diagnostic algorithm

ACTIVE COMPARATOR

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

Other: diagnostic algorithm

Usual care

NO INTERVENTION

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").

Interventions

diagnostic algorithm 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)).

Intervention: Diagnostic algorithm

Eligibility Criteria

• Age: 6 Months - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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 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
• 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

Sponsors & Collaborators

• KU Leuven: lead
• Universitaire Ziekenhuizen KU Leuven: collaborator
• University Ghent: collaborator
• Universiteit Antwerpen: collaborator
• University of Liege: collaborator
• Vrije Universiteit Brussel: collaborator
• Université Catholique de Louvain: collaborator

Study Sites (1)

GPs associated with KU Leuven

Leuven, 3000, Belgium

Location

Related Publications (5)

• 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.

  PMID: 29269559 BACKGROUND

• 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.

  PMID: 24025452 BACKGROUND

• 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.

  PMID: 27716201 BACKGROUND

• 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.

  PMID: 41016406 DERIVED

• 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.

  PMID: 34980633 DERIVED

MeSH Terms

Conditions

Infections

Results Point of Contact

• Title: Tine De Burghgraeve, PhD
• Organization: Leuven Unit Health Technology Assessment Research, KU Leuven

tine.deburghgraeve@kuleuven.be

+3216377276

Study Officials

• Jan Y Verbakel, MD, PhD

  KU Leuven

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Owing to study procedures, children, their parents and physicians will not be masked to the practices' random allocation.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Doctor

Model Details: multicentre, cluster-randomized, parallel group pragmatic trial

Study Record Dates

• First Submitted: July 2, 2020
• First Posted: July 14, 2020
• Study Start: January 6, 2021
• Primary Completion: February 1, 2024
• Study Completion: April 24, 2024
• Last Updated: April 23, 2025
• Results First Posted: April 23, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Study protocol is published and accessible. SAP, CSR, ICF and analytical code will be available after publishing the results in a medical journal. Individual patient data from this trial will not be published in the public domain.
• Access Criteria: Individual patient data from this trial will not be published in the public domain. Deidentified participant data is available for further analyses. Requests for data, with justification, should be sent to JYV, TDB, or RB. The trial protocol is available online for an indefinite period.

Locations

BE (1)