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. - 2025
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.
Verbakel, Jan Yvan; Burvenich, Ruben; D'hulster, Erinnet al.
Anti-Bacterial Agents; C-Reactive Protein; Humans; Belgium; Male; Female; Infant; Child; Child, Preschool; Primary Health Care; Acute Disease; Practice Patterns, Physicians'; Decision Support Techniques; Antimicrobial Stewardship; Anti-Bacterial Agents/therapeutic use; C-Reactive Protein/analysis; Point-of-Care Testing; Decision Trees; Medicine (all)
Abstract :
[en] [en] BACKGROUND: Antimicrobial resistance is a global health threat. Many children with acute illness in ambulatory care are unnecessarily prescribed antibiotics. We assessed the clinical effectiveness of a clinical decision tool for these children, including a validated decision tree, guided point-of-care C-reactive protein testing (POCT of CRP), and safety-netting advice.
METHODS: ARON was a multicentre, unblinded, pragmatic, cluster-randomised, controlled trial conducted at eligibile Belgian general practitioner and community paediatrician practices able to recruit children with acute illness consecutively, and not already doing POCT of CRP. Practices were allocated (1:1) with equal size (n=4) block randomisation to the clinical decision tool or usual care, stratified by recruiting academic centre. Children with acute illness aged 6 months to 12 years were recruited and followed up for 30 days. The coprimary outcomes were antibiotic prescribing at the index consultation (tested for superiority), as well as recovery time, additional testing, follow-up visits, and antibiotic prescribing after index consultation (all tested for non-inferiority with margins of 1 day, 3%, 4%, and 2%, respectively). Coprimary outcomes were analysed with logistic regression, accounting for practice clustering, study arm, and age in the intention-to-treat population, except recovery time, which was analysed with Cox regression adjusting for the same covariates. Safety was assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT04470518) and is completed.
FINDINGS: Of 171 eligible practices, we randomly allocated 82 to the intervention group and 89 to the usual care group. Between Feb 24, 2021, and Dec 29, 2023, 7049 participants were screened, of whom 6760 were deemed eligible. Five patients in each study arm were excluded, so we analysed data from 6750 participants (2988 in the intervention group and 3762 in the control group; 3447 [51%] boys, 3302 [49%] girls, one [<1%] did not specify). The intervention significantly reduced antibiotic prescribing at the index consultation (466 [16%] vs 817 [22%], adjusted odds ratio 0·72 [95% CI 0·55-0·94]; p=0·017). Recovery time (adjusted mean difference -0·1 day [95% CI -0·5 to 0·3]), additional testing (adjusted absolute risk reduction [aARR] 2·0% [-1·7 to 5·0]), follow-up visits (aARR 2·8% [-0·9 to 6·1]), and antibiotic prescribing after index consultation (aARR 2·4% [0·2 to 4·2]) were all non-inferior in the intervention group versus the control group. 90 (88%) of 102 adverse events were serious (30 [1%] in the intervention group and 60 [2%] in the control group); none were deemed related to the study procedures. No child died throughout the trial.
INTERPRETATION: The clinical decision tool reduced antibiotic prescribing in children without causing harm. Our results support its broader dissemination and implementation to improve the management of acutely ill children in ambulatory care.
FUNDING: Belgian Health Care Knowledge Centre.
Disciplines :
General & internal medicine
Author, co-author :
Verbakel, Jan Yvan; Leuven Unit for Health Technology Assessment Research (LUHTAR), Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium, Academic Centre for General Practice, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium. Electronic address: jan.verbakel@kuleuven.be
Burvenich, Ruben; Leuven Unit for Health Technology Assessment Research (LUHTAR), Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium, Academic Centre for General Practice, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium, Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
D'hulster, Erinn; Leuven Unit for Health Technology Assessment Research (LUHTAR), Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium, Academic Centre for General Practice, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium, Department of Family Medicine and Population Health (FAMPOP), University of Antwerp, Wilrijk, Belgium
De Rop, Liselore; Leuven Unit for Health Technology Assessment Research (LUHTAR), Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium, Academic Centre for General Practice, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
Van den Bruel, Ann; Academic Centre for General Practice, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
Anthierens, Sibyl; Department of Family Medicine and Population Health (FAMPOP), University of Antwerp, Wilrijk, Belgium, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Wilrijk, Belgium
Coenen, Samuel; Department of Family Medicine and Population Health (FAMPOP), University of Antwerp, Wilrijk, Belgium, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Wilrijk, Belgium
De Sutter, An; Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
Heytens, Stefan; Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
Joly, Louise ; Université de Liège - ULiège > Département des sciences cliniques > Médecine générale
Laenen, Annouschka; Leuven Biostatistics and Statistical Bioinformatics Centre (L-BioStat), Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
Luyten, Jeroen; Leuven Unit for Health Technology Assessment Research (LUHTAR), Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium, Leuven Institute for Healthcare Policy, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
De Burghgraeve, Tine; Leuven Unit for Health Technology Assessment Research (LUHTAR), Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium, Academic Centre for General Practice, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
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.
This study was supported by Belgian Health Care Knowledge Centre (KCE), as part of their KCE Trials programme, funding the ARON trial (KCE18-1137). The views expressed in this publication are those of the authors and not necessarily those of KCE. We thank all participating physicians and practice staff, the recruited children, and their parents or legal guardians for their invaluable cooperation in this trial. We also thank the Steering Committee, Universitaire Ziekenhuizen Leuven Clinical Trial Centre, and all study coordinators from the six participating academic centres. During the preparation of this work, the authors used OpenAI's ChatGPT\u20134\u00B70 in order to improve language and readability. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.
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