FarmaCHUSLab Group, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain.
Pharmacy Department, University Clinical Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
BMJ Open. 2024 Oct 29;14(10):e087465. doi: 10.1136/bmjopen-2024-087465.
Linezolid is a broadly used antibiotic to treat complicated infections caused by gram-positive bacteria. Therapeutic drug monitoring of linezolid concentrations is recommended to maximise its efficacy and safety, mainly haematological toxicity. Different pharmacokinetic/pharmacodynamic targets have been proposed to improve linezolid exposure: the ratio of the area under the concentration-time curve during a 24-hour period to minimum inhibitory concentration (MIC) between 80 and 120; percentage of time that the drug concentration remains above the MIC during a dosing interval greater than 85% and the trough concentration between 2 and 7 mg/L. This clinical trial aims to evaluate the safety, efficacy and the clinical and economic utility of personalised dosing of linezolid using Bayesian forecasting methods to attain pharmacokinetic/pharmacodynamic targets, known as model-informed precision dosing.
This is a pragmatic, multicentre, randomised, parallel, controlled, phase IV and low intervention trial. Participants will be randomly assigned 1:1 to each group (n=346 per group). Control group will receive the standard dose of linezolid. Intervention group will receive personalised dosage of linezolid based on pharmacokinetic-pharmacodynamic adjustments. The primary outcome will be the incidence of thrombocytopenia in both groups.
This protocol was approved by the Ethical Committee of the Investigation with Medicines of Galicia (code 2022/140) and authorised by the Spanish Agency for Medicines and Medical Devices. The trial is implemented in accordance with the Declaration of Helsinki and the international ethical and scientific quality standard, the Good Clinical Practice. The results will be published in peer-reviewed journals.
EudraCT registration code: 2022-000144-30.
利奈唑胺是一种广泛使用的抗生素，用于治疗由革兰阳性菌引起的复杂感染。为了最大限度地提高其疗效和安全性，特别是血液学毒性，建议对利奈唑胺浓度进行治疗药物监测。已经提出了不同的药代动力学/药效学目标来改善利奈唑胺的暴露：24 小时期间浓度-时间曲线下面积与最低抑菌浓度（MIC）的比值为 80 至 120；在给药间隔期间药物浓度超过 MIC 的时间百分比大于 85%，谷浓度在 2 至 7mg/L 之间。这项临床试验旨在评估使用贝叶斯预测方法实现药代动力学/药效学目标的个体化利奈唑胺给药的安全性、疗效以及临床和经济实用性，这种方法被称为基于模型的精准给药。
这是一项实用的、多中心的、随机的、平行的、对照的、四期和低干预性试验。参与者将被随机分配到每组 1:1（每组 346 人）。对照组将接受标准剂量的利奈唑胺。干预组将根据药代动力学/药效学调整接受个体化剂量的利奈唑胺。主要结局将是两组中血小板减少症的发生率。
本方案已获得加利西亚药物研究伦理委员会（代码 2022/140）的批准，并获得西班牙药品和医疗器械管理局的授权。试验符合《赫尔辛基宣言》和国际伦理和科学质量标准，即良好临床实践。结果将发表在同行评议的期刊上。
EudraCT 注册号：2022-000144-30。
