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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2024年10月10日

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  • Pieter A. De Cock,
  • Roos Colman,
  • Anca Amza,
  • Peter De Paepe,
  • Hans De Pla,
  • Lieselot Vanlanduyt,
  • Dimitri Van der Linden,
  • Petra Schelstraete,
  • Filip Cools,
  • Alexander Clarysse,
  • Phebe Debouver,
  • Dominique Biarent,
  • Daphne Vania Vens,
  • Anne Smits,
  • Valerie Godart,
  • Sophie Vanhaesebrouck,
  • Evelyn Dhont,
  • Victoria Bordon,
  • Reiner Mauel,
  • Jutte Van Der Werff Ten Bosch,
  • Marleen Renard,
  • Franciscus Derriks,
  • Olivier Danhaive,
  • Fiammetta Piersigilli,
  • Houtekie Laurent,
  • An van Damme,
  • Lidvine Boland,
  • Koenraad Smets,
  • Alexandra Zecic,
  • Linde Goossens,
  • Kris De Coen,
  • Annelies Keymeulen,
  • Lara Garabedian,
  • Julie De Meulemeester,
  • Naessens Pauline,
  • Tom Schepens,
  • Emma Beel,
  • Jef Willems,
  • Annick de Jaeger,
  • Ann Verrijckt,
  • Bram De Wilde,
  • Tiene Bauters,
  • Nele Clottens,
  • Sarah Mertens,
  • Fleur Camfermann,
  • Michael Sonnaert,
  • Julie Lefevere,
  • Barbara De Bisschop,
  • Floortje Krechting,
  • Lissa De Potter,
  • James d’Haese,
  • Marit Sijmons,
  • Tine Francois,
  • Xavier Berette-Piccoli,
  • Shancy Rooze,
  • Alfredo Vicinanza,
  • Vanessa Guy Viterbo,
  • Montserrat Sierra Colomina,
  • Laura Slegers,
  • Zoe Vander Elst,
  • Anneleen Dereymaker,
  • An Eerdekens,
  • Liesbeth Thewissen,
  • Maissa Rayyan,
  • Laurien Vanbuggenhout,
  • Marie Julie Debuf,
  • Sarah Verbeeck,
  • Karlijn van Damme,
  • Anne Uyttebroeck,
  • Veerle Labarque,
  • Heidi Segers,
  • Katrien Cosaert,
  • Lotte Vander Elst,
  • Eva Vanlaer,
  • Isabelle Ceuterick,
  • Olga Chatzis,
  • Matthieu Deltombe,
  • Bastien Tossens,
  • Arnaud Nevraumont,
  • Louise Guillaume,
  • Martin Vanderdonck,
  • Meryem Benamour,
  • Mohammad Panahandeh,
  • Veerle Mondelaers,
  • Leen Willems,
  • Leentje Peetermans,
  • Astrid Haenecour,
  • Maëlle de Ville de Goyet,
  • Bénédicte Brichard,
  • Manon Le Roux,
  • Evelien Snauwaert,
  • Charlotte Clauwaert,
  • Hanife Kokur,
  • Stefanie De Buyser

摘要

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