A multicentric, randomized, controlled clinical trial to study the impact of bedside model-informed precision dosing of vancomycin in critically ill children-BENEFICIAL trial.

Publisher: BioMed Central Country of Publication: England NLM ID: 101263253 Publication Model: Electronic Cited Medium: Internet ISSN: 1745-6215 (Electronic) Linking ISSN: 17456215 NLM ISO Abbreviation: Trials Subsets: MEDLINE

Original Publication: [London] : BioMed Central, 2006-

Anti-Bacterial Agents*/administration & dosage ; Anti-Bacterial Agents*/pharmacokinetics ; Anti-Bacterial Agents*/adverse effects ; Area Under Curve* ; Critical Illness* ; Drug Monitoring*/methods ; Vancomycin*/administration & dosage ; Vancomycin*/pharmacokinetics ; Vancomycin*/adverse effects; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Microbial Sensitivity Tests ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic

Background: Vancomycin is a commonly prescribed antibiotic to treat serious Gram-positive infections in children. The efficacy of vancomycin is known to be directly related to the pharmacokinetic/pharmacodynamic (PK/PD) index of the area under the concentration-time curve (AUC) divided by the minimal inhibitory concentration (MIC) of the pathogen. In most countries, steady-state plasma concentrations are used as a surrogate parameter for this target AUC/MIC, but this practice has some drawbacks. Hence, AUC-based dosing using model-informed precision dosing (MIPD) tools has been proposed for increasing the target attainment rate and reducing vancomycin-related nephrotoxicity. Solid scientific evidence for these claimed benefits is lacking in children. This randomized controlled trial aims to investigate the large-scale utility of MIPD dosing of vancomycin in critically ill children.
Methods: Participants from 14 neonatal intensive care, pediatric intensive care, and pediatric hemo-oncology ward units from 7 hospitals are randomly allocated to the intervention or standard-of-care comparator group. In the intervention group, a MIPD dosing calculator is used for AUC-based dosing, in combination with extra sampling for therapeutic drug monitoring in the first hours of treatment, as compared to standard-of-care. An AUC24h between 400 and 600 is targeted, assuming an MIC of 1 mg/L. Patients in the comparator group receive standard-of-care dosing and monitoring according to institutional guidelines. The primary endpoint is the proportion of patients reaching the target AUC24h/MIC of 400-600 between 24 and 48 h after the start of vancomycin treatment. Secondary endpoints are the proportion of patients with (worsening) acute kidney injury during vancomycin treatment, the proportion of patients reaching target AUC24h/MIC of 400-600 between 48 and 72 h after the start of vancomycin treatment, time to clinical cure, ward unit length-of-stay, hospital length-of-stay, and 30-day all-cause mortality.
Discussion: This trial will clarify the propagated benefits and provide new insights into how to optimally monitor vancomycin treatment in critically ill children.
Trial Registration: Eudract number: 2019-004538-40. Registered on 2020-09-08 ClinicalTrials.gov NCT046666948. Registered on 2020-11-28.
(© 2024. The Author(s).)

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Investigator: P Schelstraete; F Cools; A Clarysse; P Debouver; D Biarent; DV Vens; A Smits; V Godart; S Vanhaesebrouck; E Dhont; V Bordon; R Mauel; J Van Der Werff Ten Bosch; M Renard; F Derriks; O Danhaive; F Piersigilli; H Laurent; A van Damme; L Boland; K Smets; A Zecic; L Goossens; K De Coen; A Keymeulen; L Garabedian; J De Meulemeester; N Pauline; T Schepens; E Beel; J Willems; A de Jaeger; A Verrijckt; B De Wilde; T Bauters; N Clottens; S Mertens; F Camfermann; M Sonnaert; J Lefevere; B De Bisschop; F Krechting; L De Potter; J d'Haese; M Sijmons; T Francois; X Berette-Piccoli; S Rooze; A Vicinanza; VG Viterbo; MS Colomina; L Slegers; ZV Elst; A Dereymaker; A Eerdekens; L Thewissen; M Rayyan; L Vanbuggenhout; MJ Debuf; S Verbeeck; K van Damme; A Uyttebroeck; V Labarque; H Segers; K Cosaert; LV Elst; E Vanlaer; I Ceuterick; O Chatzis; M Deltombe; B Tossens; A Nevraumont; L Guillaume; M Vanderdonck; M Benamour; M Panahandeh; V Mondelaers; L Willems; L Peetermans; A Haenecour; MV Goyet; B Brichard; M Le Roux; E Snauwaert; C Clauwaert; H Kokur; S De Buyser
Keywords: Area under the concentration–time curve dosing; Critically ill children; Model-informed precision dosing; Randomized controlled trial; Therapeutic drug monitoring; Vancomycin

0 (Anti-Bacterial Agents)
6Q205EH1VU (Vancomycin)

Date Created: 20241010 Date Completed: 20241011 Latest Revision: 20241017

20241018

PMC11466033

10.1186/s13063-024-08512-z

39390583