<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04470518</url>
  </required_header>
  <id_info>
    <org_study_id>S62005</org_study_id>
    <nct_id>NCT04470518</nct_id>
  </id_info>
  <brief_title>Impact of Clinical Guidance &amp; Point-of-care CRP in Children: the ARON Project</brief_title>
  <acronym>ARON</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>KU Leuven</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Universitaire Ziekenhuizen KU Leuven</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Ghent</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Universiteit Antwerpen</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Liege</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Vrije Universiteit Brussel</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Université Catholique de Louvain</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>KU Leuven</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Impact of clinical guidance &amp; point-of-care CRP test in children: the ARON project Trial&#xD;
      Design: multicentre, cluster-randomized, parallel group pragmatic trial Trial Participants&#xD;
      and setting: Children aged 6 months to 12 years of age with an acute illness episode&#xD;
      presenting to in-hours general practice or out-of-hospital community paediatrics offices&#xD;
&#xD;
      Intervention(s) Diagnostic algorithm:&#xD;
&#xD;
        1. Clinical decision tree: clinician's gut feeling something is wrong, dyspnea, temperature&#xD;
           ≥40ºC&#xD;
&#xD;
        2. YES to any : point-of-care CRP ≥5mg/L: additional testing or refer to secondary care&#xD;
           &lt;5mg/L: safety netting*, only prescribe antibiotics if advised (guidelines)&#xD;
&#xD;
        3. NO to all : are AB considered? YES : point-of-care CRP ≥5mg/L: safety netting*, only&#xD;
           prescribe antibiotics if advised (guidelines) &lt;5mg/L: safety netting*, do not prescribe&#xD;
           antibiotics NO: safety netting&#xD;
&#xD;
           *safety netting advice:&#xD;
&#xD;
             -  inform parents on what to expect and what to look out for&#xD;
&#xD;
             -  interactive parent information booklet based on previous research&#xD;
&#xD;
           Control: Diagnosis and Treatment/Management as per usual care:&#xD;
&#xD;
           - guidance on AB prescribing:&#xD;
&#xD;
           o Belgische Commissie voor de Coördinatie van het Antibioticabeleid (BAPCOC) guide&#xD;
           (updated November 2019)&#xD;
&#xD;
           o RIZIV consensus meeting report &quot;Antibiotics in children in ambulatory care&quot;&#xD;
&#xD;
           Primary Endpoint: Antibiotic prescribing rate at index consultation&#xD;
&#xD;
           Secondary Endpoint(s)&#xD;
&#xD;
           - time until full clinical recovery (during follow up (day 1 to day 30))&#xD;
&#xD;
           - additional investigations (at index consultation and/or during follow up (day 1 to day&#xD;
           30))&#xD;
&#xD;
           - re-consultation (during follow up (day 1 to day 30))&#xD;
&#xD;
           - antibiotic prescribing rate (during follow up (day 1 to day 30))&#xD;
&#xD;
           Exploratory endpoints at the index consultation:&#xD;
&#xD;
             -  additional investigations (X-Ray, blood tests, urine tests, etc.)&#xD;
&#xD;
           During a follow-up period (day 1 to day 30):&#xD;
&#xD;
           - referral to hospital&#xD;
&#xD;
           - additional investigations (X-Ray, blood tests, urine tests, etc.)&#xD;
&#xD;
             -  patients with full clinical recovery at day 7 and day 30&#xD;
&#xD;
             -  admission to hospital&#xD;
&#xD;
             -  mortality&#xD;
&#xD;
             -  cost-effectiveness&#xD;
&#xD;
             -  patient satisfaction&#xD;
&#xD;
             -  qualitative study: endpoints&#xD;
&#xD;
           Planned Sample Size: 6111 Timing of the intervention: Intervention at index consultation&#xD;
           (at presentation to primary care) Follow-up duration: 30 days follow-up Duration of the&#xD;
           trial (FPI-CSR): 33 months&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators aim to strengthen the assessment of acutely ill children in primary care,&#xD;
      by introducing a diagnostic algorithm that can decrease antibiotic prescribing.&#xD;
&#xD;
      In light of the prior evidence and its results so far, the ARON trial will test the impact of&#xD;
      a diagnostic algorithm including a standardised clinical assessment, a POC CRP test, and&#xD;
      safety netting advice.&#xD;
&#xD;
      Therefore, the investigators propose to assess the clinical and cost-effectiveness of a&#xD;
      diagnostic algorithm which includes a decision tree, POC CRP and safety netting advice in&#xD;
      acutely ill children aged 6 months to 12 years of age presenting to ambulatory care, on AB&#xD;
      prescribing, referral/admission to hospital, additional testing, mortality, and patient&#xD;
      satisfaction.&#xD;
&#xD;
      More specifically, the investigators' research question is whether this diagnostic algorithm&#xD;
      is able to safely reduce antibiotic prescribing in acutely ill children presenting to&#xD;
      ambulatory care.&#xD;
&#xD;
      The decision whether or not to conduct a POC CRP test will depend on the standardized&#xD;
      clinical assessment, i.e. a validated clinical decision tree, and subsequently for low-risk&#xD;
      children on the intention to prescribe AB.&#xD;
&#xD;
      The investigators will provide clear evidence-based guidance on how to interpret the CRP test&#xD;
      result as outlined below.&#xD;
&#xD;
      A process evaluation will examine how clinicians use CRP testing in their practice and how&#xD;
      parents experience these consultations.&#xD;
&#xD;
      The investigators propose a study, where children (6 months to 12 years of age) will be&#xD;
      randomised to (a) a diagnostic algorithm with CRP testing and specific guidance on when to&#xD;
      prescribe AB or (b) usual care. CRP testing will be done using a finger prick test (result&#xD;
      within 4 minutes). The CRP level will then be given to the clinician who will communicate the&#xD;
      result to the child/parents.&#xD;
&#xD;
      The investigators aim to recruit 6111 children and will collect data registered by the&#xD;
      participating physician, from the child's health record and children/parents directly. The&#xD;
      investigators will describe how the intervention has worked in practice and how&#xD;
      clinicians/parents have experienced these consultations.&#xD;
&#xD;
      Guidance will be part of a diagnostic algorithm which includes clinically guided POC CRP&#xD;
      testing and safety netting advice to inform parents on what to expect and what to look out&#xD;
      for.&#xD;
&#xD;
      Individual interviews will be conducted with clinicians and parents taking part in the trial&#xD;
      within 30 days after the first contact consultation, to explore the social processes&#xD;
      influencing embedding of the intervention within practice, and behaviour change techniques.&#xD;
&#xD;
      These individual telephone interviews will be performed with a selection of parents to&#xD;
      address whether their concerns were discussed appropriately and whether their expectations&#xD;
      were met and how they experienced the consultation and/or POC CRP testing.&#xD;
&#xD;
      The safety-netting advice will be supported by a parent information booklet, based on&#xD;
      previous research (the &quot;When should I worry&quot;-interactive booklet (a guide to Coughs, Colds,&#xD;
      Earache &amp; Sore Throats), the &quot;Mijn kind heeft koorts&quot; booklet (Eefje de Bont,&#xD;
      www.thuisarts.nl), and the &quot;Caring for children with coughs&quot;-leaflet (information about how&#xD;
      to look after a child who has a cough and when to see the doctor)).&#xD;
&#xD;
      The findings of this study could change the practice of ambulatory care physicians and might&#xD;
      be of great interest to parents and childcare providers. The investigators will publish the&#xD;
      findings of this research in academic journals, present at national conferences and discuss&#xD;
      results with groups responsible for the national guidance on how to assess acutely ill&#xD;
      children (Domus Medica, SSMG).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 6, 2021</start_date>
  <completion_date type="Anticipated">June 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>multicentre, cluster-randomized, parallel group pragmatic trial</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Owing to study procedures, children, their parents and physicians will not be masked to the practices' random allocation.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>antibiotic prescribing rate at index consultation (immediate or delayed)</measure>
    <time_frame>This outcome will be registered immediately at the index consultation (immediately after the intervention)</time_frame>
    <description>The primary outcome is the proportion of subjects who were prescribed antibiotic treatment (both immediate and delayed) at the index consultation as recorded by the treating physician.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical recovery during follow-up</measure>
    <time_frame>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)</time_frame>
    <description>the duration (in days) until reaching full clinical recovery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Additional investigations at index consultation and/or during follow-up</measure>
    <time_frame>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</time_frame>
    <description>- the proportion of subjects receiving additional testing (including, but not limited to (X-Ray, blood tests, urine tests) at index consultation (day 0) and/or during follow-up (day 1 to day 30)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Re-consultation during follow-up</measure>
    <time_frame>This outcome will be checked from the patient health record from first day to day 30 after the intervention</time_frame>
    <description>- the proportion of subjects who re-consulted their physician during follow-up (day 1 to day 30)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antibiotic prescribing rate during follow-up</measure>
    <time_frame>This outcome will be checked from the patient health record first day to day 30 after the intervention</time_frame>
    <description>- the proportion of subjects who were prescribed antibiotic treatment during follow-up (day 1 to day 30)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>additional testing at index consultation</measure>
    <time_frame>immediately after the intervention</time_frame>
    <description>the proportion of subjects receiving additional testing (including, but not limited to (X-Ray, blood tests, urine tests) at index consultation (day 0)</description>
  </other_outcome>
  <other_outcome>
    <measure>additional testing during follow-up</measure>
    <time_frame>during follow-up from first day to day 30 after the intervention</time_frame>
    <description>the proportion of subjects receiving additional testing (including, but not limited to (X-Ray, blood tests, urine tests) during follow-up (day 1 to day 30)</description>
  </other_outcome>
  <other_outcome>
    <measure>referral to hospital at day 0</measure>
    <time_frame>immediately after the intervention</time_frame>
    <description>the proportion of subjects referred to hospital at index consultation (day 0)</description>
  </other_outcome>
  <other_outcome>
    <measure>referral to hospital during follow-up</measure>
    <time_frame>during follow-up from first day to day 30 after the intervention</time_frame>
    <description>the proportion of subjects referred to hospital during follow-up (day 1 to day 30)</description>
  </other_outcome>
  <other_outcome>
    <measure>admission to hospital at day 0</measure>
    <time_frame>immediately after the intervention</time_frame>
    <description>the proportion of subjects admitted to hospital at index consultation (day 0)</description>
  </other_outcome>
  <other_outcome>
    <measure>admission to hospital during follow-up</measure>
    <time_frame>during follow-up from first day to day 30 after the intervention</time_frame>
    <description>the proportion of subjects admitted to hospital during follow-up (day 1 to day 30)</description>
  </other_outcome>
  <other_outcome>
    <measure>mortality at day 0</measure>
    <time_frame>immediately after the intervention</time_frame>
    <description>the proportion of subjects who died at index consultation (day 0)</description>
  </other_outcome>
  <other_outcome>
    <measure>mortality during follow up</measure>
    <time_frame>during follow-up from first day to day 30 after the intervention</time_frame>
    <description>the proportion of subjects who died during follow-up (day 1 to day 30)</description>
  </other_outcome>
  <other_outcome>
    <measure>clinical recovery at day 7</measure>
    <time_frame>at day 7 after the intervention</time_frame>
    <description>the proportion of subjects with full clinical recovery at day 7</description>
  </other_outcome>
  <other_outcome>
    <measure>clinical recovery at day 30</measure>
    <time_frame>at day 30 after the intervention</time_frame>
    <description>the proportion of subjects with full clinical recovery at day 30</description>
  </other_outcome>
  <other_outcome>
    <measure>patient's experience through semi-structured interviews</measure>
    <time_frame>within 7 days after the intervention</time_frame>
    <description>Patient's experience through semi-structured interviews with pre-defined topic guide</description>
  </other_outcome>
  <other_outcome>
    <measure>Parent's experience through semi-structured interviews</measure>
    <time_frame>within 7 days after the intervention</time_frame>
    <description>Parent's experience through semi-structured interviews with pre-defined topic guide</description>
  </other_outcome>
  <other_outcome>
    <measure>Physician's experience through semi-structured interviews</measure>
    <time_frame>within 7 days after the intervention</time_frame>
    <description>Physician's experience through semi-structured interviews with pre-defined topic guide</description>
  </other_outcome>
  <other_outcome>
    <measure>Cost-effectiveness of the intervention</measure>
    <time_frame>will be assessed retrospectively after data collection has finished (24 months of recruitment)</time_frame>
    <description>Cost-effectiveness of the intervention: healthcare expenditures in terms of hospitalization, consultations, pharmaceuticals (reimbursed and non-reimbursed), productivity, quality of life</description>
  </other_outcome>
  <other_outcome>
    <measure>Adherence to the diagnostic algorithm</measure>
    <time_frame>immediately after the intervention</time_frame>
    <description>proportion of consultation in which the physician did not adhere to the diagnostic algorithm</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">6111</enrollment>
  <condition>Infection</condition>
  <arm_group>
    <arm_group_label>Intervention: Diagnostic algorithm</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>diagnostic algorithm including a standardised clinical assessment, a Point-of-care C-reactive protein test, and safety netting advice</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Usual care</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>In the control arm, patients will receive 'usual care' left at the discretion of the treating physician.&#xD;
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.&#xD;
They are expected (but not forced) to follow the Belgian guidelines (as described in &quot;BAPCOC National guidelines and the RIZIV consensus meeting &quot;Rational use of antibiotics in children&quot;).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>diagnostic algorithm</intervention_name>
    <description>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).&#xD;
The safety-netting advice will be supported by a parent information booklet, based on previous research (the &quot;When should I worry&quot;-interactive booklet (a guide to Coughs, Colds, Earache &amp; Sore Throats), the &quot;Mijn kind heeft koorts&quot; booklet (Eefje de Bont, www.thuisarts.nl), and the &quot;Caring for children with coughs&quot;-leaflet (information about how to look after a child who has a cough and when to see the doctor)).</description>
    <arm_group_label>Intervention: Diagnostic algorithm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria for practices:&#xD;
&#xD;
          -  Being able to recruit acutely ill children (ideally consecutively)&#xD;
&#xD;
          -  Agree to the terms of the clinical study agreement.&#xD;
&#xD;
        Exclusion Criteria for practices:&#xD;
&#xD;
          -  Currently using a POC CRP device as part of their routine care&#xD;
&#xD;
          -  No practices will be excluded on other grounds than the above. Age, demographics,&#xD;
             geographic region will not be used to exclude eligible practices. This will provide us&#xD;
             with a real-life, representative subset of ambulatory care physicians.&#xD;
&#xD;
        Inclusion criteria for children&#xD;
&#xD;
          -  Children aged 6 months to 12 years, provided informed consent can be obtained&#xD;
&#xD;
          -  presenting with an acute illness episode that started maximum 10 days before the index&#xD;
             consultation&#xD;
&#xD;
        Exclusion criteria for children&#xD;
&#xD;
          -  Children who were previously included in this trial&#xD;
&#xD;
          -  children with an underlying known chronic condition (e.g. asthma, immune deficiency)&#xD;
&#xD;
          -  clinically unstable warranting immediate care&#xD;
&#xD;
          -  immunosuppressant medication taken in the previous 30 days&#xD;
&#xD;
          -  trauma as the main presenting problem&#xD;
&#xD;
          -  antibiotics taken in the previous 7 days&#xD;
&#xD;
          -  Unwillingness or inability to provide informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jan Y Verbakel, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>KU Leuven</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Tine De Burghgraeve, PhD</last_name>
    <phone>+3216 37 76 72</phone>
    <email>tine.deburghgraeve@kuleuven.be</email>
  </overall_contact>
  <location>
    <facility>
      <name>GPs associated with KU Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tine De Burghgraeve</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <reference>
    <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>
    <PMID>29269559</PMID>
  </reference>
  <reference>
    <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>
    <PMID>24025452</PMID>
  </reference>
  <reference>
    <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. Erratum In: BMC Med. 2017 May 2;15(1):93.</citation>
    <PMID>27716201</PMID>
  </reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>July 2, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>February 8, 2023</last_update_submitted>
  <last_update_submitted_qc>February 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>KU Leuven</investigator_affiliation>
    <investigator_full_name>Jan Verbakel</investigator_full_name>
    <investigator_title>Professor Doctor</investigator_title>
  </responsible_party>
  <keyword>antibiotic prescription</keyword>
  <keyword>infections</keyword>
  <keyword>decision tree</keyword>
  <keyword>point-of-care C-reactive protein test</keyword>
  <keyword>safetynet advice</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04470518
org study id: S62005
nct id: NCT04470518
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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: 6111 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): 33 months
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 6111 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).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: multicentre, cluster-randomized, parallel group pragmatic trial
primary purpose: Other
masking: None (Open Label)
masking description: Owing to study procedures, children, their parents and physicians will not be masked to the practices' random allocation.
measure: antibiotic prescribing rate at index consultation (immediate or delayed)
time frame: This outcome will be registered immediately at the index consultation (immediately after the intervention)
description: The primary outcome is the proportion of subjects who were prescribed antibiotic treatment (both immediate and delayed) at the index consultation as recorded by the treating physician.
measure: Clinical recovery during follow-up
time frame: 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)
description: the duration (in days) until reaching full clinical recovery
measure: Additional investigations at index consultation and/or during follow-up
time frame: 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
description: - the proportion of subjects receiving additional testing (including, but not limited to (X-Ray, blood tests, urine tests) at index consultation (day 0) and/or during follow-up (day 1 to day 30)
measure: Re-consultation during follow-up
time frame: This outcome will be checked from the patient health record from first day to day 30 after the intervention
description: - the proportion of subjects who re-consulted their physician during follow-up (day 1 to day 30)
measure: Antibiotic prescribing rate during follow-up
time frame: This outcome will be checked from the patient health record first day to day 30 after the intervention
description: - the proportion of subjects who were prescribed antibiotic treatment during follow-up (day 1 to day 30)
measure: additional testing at index consultation
time frame: immediately after the intervention
description: the proportion of subjects receiving additional testing (including, but not limited to (X-Ray, blood tests, urine tests) at index consultation (day 0)
measure: additional testing during follow-up
time frame: during follow-up from first day to day 30 after the intervention
description: the proportion of subjects receiving additional testing (including, but not limited to (X-Ray, blood tests, urine tests) during follow-up (day 1 to day 30)
measure: referral to hospital at day 0
time frame: immediately after the intervention
description: the proportion of subjects referred to hospital at index consultation (day 0)
measure: referral to hospital during follow-up
time frame: during follow-up from first day to day 30 after the intervention
description: the proportion of subjects referred to hospital during follow-up (day 1 to day 30)
measure: admission to hospital at day 0
time frame: immediately after the intervention
description: the proportion of subjects admitted to hospital at index consultation (day 0)
measure: admission to hospital during follow-up
time frame: during follow-up from first day to day 30 after the intervention
description: the proportion of subjects admitted to hospital during follow-up (day 1 to day 30)
measure: mortality at day 0
time frame: immediately after the intervention
description: the proportion of subjects who died at index consultation (day 0)
measure: mortality during follow up
time frame: during follow-up from first day to day 30 after the intervention
description: the proportion of subjects who died during follow-up (day 1 to day 30)
measure: clinical recovery at day 7
time frame: at day 7 after the intervention
description: the proportion of subjects with full clinical recovery at day 7
measure: clinical recovery at day 30
time frame: at day 30 after the intervention
description: the proportion of subjects with full clinical recovery at day 30
measure: patient's experience through semi-structured interviews
time frame: within 7 days after the intervention
description: Patient's experience through semi-structured interviews with pre-defined topic guide
measure: Parent's experience through semi-structured interviews
time frame: within 7 days after the intervention
description: Parent's experience through semi-structured interviews with pre-defined topic guide
measure: Physician's experience through semi-structured interviews
time frame: within 7 days after the intervention
description: Physician's experience through semi-structured interviews with pre-defined topic guide
measure: Cost-effectiveness of the intervention
time frame: will be assessed retrospectively after data collection has finished (24 months of recruitment)
description: Cost-effectiveness of the intervention: healthcare expenditures in terms of hospitalization, consultations, pharmaceuticals (reimbursed and non-reimbursed), productivity, quality of life
measure: Adherence to the diagnostic algorithm
time frame: immediately after the intervention
description: proportion of consultation in which the physician did not adhere to the diagnostic algorithm
arm group label: Intervention: Diagnostic algorithm
arm group type: Active Comparator
description: diagnostic algorithm including a standardised clinical assessment, a Point-of-care C-reactive protein test, and safety netting advice
arm group label: Usual care
arm group type: No Intervention
description: 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").
intervention type: Other
intervention name: diagnostic algorithm
description: 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)).
arm group label: Intervention: Diagnostic algorithm
criteria: 
gender: All
minimum age: 6 Months
maximum age: 12 Years
healthy volunteers: No
last name: Jan Y Verbakel, MD, PhD
role: Principal Investigator
affiliation: KU Leuven
last name: Tine De Burghgraeve, PhD
phone: +3216 37 76 72
email: tine.deburghgraeve@kuleuven.be
facility: 
status: Recruiting
contact: 
country: Belgium
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.
PMID: 29269559
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.
PMID: 24025452
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. Erratum In: BMC Med. 2017 May 2;15(1):93.
PMID: 27716201
responsible party type: Principal Investigator
investigator affiliation: KU Leuven
investigator full name: Jan Verbakel
investigator title: Professor Doctor
mesh term: Infections
sharing ipd: No