Clinical trial NCT04470518: Impact of Clinical Guidance & Point-of-care CRP in Children: the ARON Project
Official title: Impact of a Diagnostic Algorithm on Antibiotic Prescribing Rate and Further Management of Acutely Ill Children Presenting to Ambulatory Care: Multicentre, Cluster-randomized, Parallel Group Pragmatic Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infection
Keywords: antibiotic prescription
infections
decision tree
point-of-care C-reactive protein test
safetynet advice
Lead sponsor: KU Leuven
Sponsor class: OTHER
Collaborators: name: Universitaire Ziekenhuizen KU Leuven
name: University Ghent
name: Universiteit Antwerpen
name: University of Liege
name: Vrije Universiteit Brussel
name: Université Catholique de Louvain
First posted: 2020-07-14
Enrollment: 6750
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multicentre, cluster-randomized, parallel group pragmatic trial
Primary purpose: OTHER

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).

Eligibility criteria: Inclusion Criteria for practices:

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

Exclusion Criteria for practices:

* 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.

Inclusion criteria for children

* 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 for children

* 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

Primary outcomes:
measure: Antibiotic Prescribing Rate at Index Consultation (Immediate or Delayed)
timeFrame: This outcome will be registered immediately at the index consultation (immediately after the intervention)
Secondary outcomes:
measure: Clinical Recovery During Follow-up
timeFrame: 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)
measure: Additional Investigations at Index Consultation and/or During Follow-up
timeFrame: 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
measure: Re-consultation During Follow-up
timeFrame: This outcome will be checked from the patient health record from first day to day 30 after the intervention
measure: Antibiotic Prescribing Rate During Follow-up
timeFrame: This outcome will be checked from the patient health record first day to day 30 after the intervention
Other outcomes:
measure: Additional Testing at Index Consultation
timeFrame: This outcome will be registered immediately at the index consultation
measure: Additional Testing During Follow-up
timeFrame: during follow-up from first day to day 30 after the intervention
measure: Referral to Hospital at Day 0
timeFrame: This outcome will be registered immediately at the index consultation
measure: Referral to Hospital During Follow-up
timeFrame: during follow-up from first day to day 30 after the intervention
measure: Admission to Hospital at Day 0
timeFrame: This outcome will be registered immediately at the index consultation
measure: Admission to Hospital During Follow-up
timeFrame: during follow-up from first day to day 30 after the intervention
measure: Mortality at Day 0
timeFrame: This outcome will be registered immediately at the index consultation
measure: Mortality During Follow up
timeFrame: during follow-up from first day to day 30 after the intervention
measure: Clinical Recovery at Day 7
timeFrame: at day 7 after the intervention
measure: Clinical Recovery at Day 30
timeFrame: at day 30 after the intervention
measure: Patient's Experience Through Semi-structured Interviews
timeFrame: within 7 days after the intervention
measure: Parent's Experience Through Semi-structured Interviews
timeFrame: within 7 days after the intervention
measure: Physician's Experience Through Semi-structured Interviews
timeFrame: within 7 days after the intervention
measure: Cost-effectiveness of the Intervention
timeFrame: will be assessed retrospectively after data collection has finished (24 months of recruitment)
measure: Number of Participants Whose Physician Was Non-Adherent to the Diagnostic Algorithm
timeFrame: This outcome will be registered immediately at the index consultation
Locations:
city: Leuven
country: Belgium
facility: GPs associated with KU Leuven
Study officials:
affiliation: KU Leuven
name: Jan Y Verbakel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.