Department of Hospital Pharmacy, Ghent University Hospital, Ghent, Belgium.
Department of Basic and Applied Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
Trials. 2024 Oct 10;25(1):669. doi: 10.1186/s13063-024-08512-z.
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.
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.
This trial will clarify the propagated benefits and provide new insights into how to optimally monitor vancomycin treatment in critically ill children.
Eudract number: 2019-004538-40. Registered on 2020-09-08 ClinicalTrials.gov NCT046666948. Registered on 2020-11-28.
万古霉素是一种常用于治疗儿童严重革兰氏阳性感染的抗生素。万古霉素的疗效与浓度-时间曲线下面积（AUC）除以病原体最小抑菌浓度（MIC）的药代动力学/药效学（PK/PD）指数直接相关。在大多数国家，稳态血浆浓度被用作该目标 AUC/MIC 的替代参数，但这种做法存在一些缺点。因此，已经提出了基于 AUC 的使用模型指导的精准剂量（MIPD）工具的给药，以提高目标达标率并降低万古霉素相关的肾毒性。在儿童中，缺乏这些声称的益处的坚实科学证据。本随机对照试验旨在研究 MIPD 给药在危重症儿童中的大规模应用。
来自 7 家医院的 14 个新生儿重症监护病房、儿科重症监护病房和儿科血液肿瘤病房的参与者被随机分配到干预组或标准护理对照组。在干预组中，与标准护理相比，使用基于 AUC 的 MIPD 剂量计算器进行给药，并在治疗的最初几小时内进行额外的治疗药物监测采样。目标 AUC24h 为 400-600，假设 MIC 为 1mg/L。对照组患者根据机构指南接受标准护理剂量和监测。主要终点是在万古霉素治疗开始后 24-48 小时内达到目标 AUC24h/MIC 400-600 的患者比例。次要终点是万古霉素治疗期间（恶化）急性肾损伤的患者比例、万古霉素治疗开始后 48-72 小时内达到目标 AUC24h/MIC 400-600 的患者比例、临床治愈时间、病房单位住院时间、医院住院时间和 30 天全因死亡率。
本试验将阐明已宣传的益处，并为如何优化监测危重症儿童的万古霉素治疗提供新的见解。
Eudract 编号：2019-004538-40。注册于 2020 年 9 月 8 日，ClinicalTrials.gov NCT046666948。注册于 2020 年 11 月 28 日。
