Abstract：
BACKGROUND: Critically ill patients are at risk of suboptimal beta-lactam antibiotic (beta-lactam) exposure due to the impact of altered physiology on pharmacokinetics. Suboptimal concentrations can lead to treatment failure or toxicity. Therapeutic drug monitoring (TDM) involves adjusting doses based on measured plasma concentrations and individualising dosing to improve the likelihood of improving exposure. Despite its potential benefits, its adoption has been slow, and data on implementation, dose adaptation and safety are sparse. The aim of this trial is to assess the feasibility and fidelity of implementing beta-lactam TDM-guided dosing in the intensive care unit setting.
METHODS: A beta-lactam antibiotic Dose AdaPtation feasibility randomised controlled Trial using Therapeutic Drug Monitoring (ADAPT-TDM) is a single-centre, unblinded, feasibility randomised controlled trial aiming to enroll up to 60 critically ill adult participants (≥18 years). TDM and dose adjustment will be performed daily in the intervention group; the standard of care group will undergo plasma sampling, but no dose adjustment. The main outcomes include: (1) feasibility of recruitment, defined as the number of participants who are recruited from a pool of eligible participants, and (2) fidelity of TDM, defined as the degree to which TDM as a test is delivered as intended, from accurate sample collection, sample processing to result availability. Secondary outcomes include target attainment, uptake of TDM-guided dosing and incidence of neurotoxicity, hepatotoxicity and nephrotoxicity.
BACKGROUND: This study has been approved by the Alfred Hospital human research ethics committee, Office of Ethics and Research Governance (reference: Project No. 565/22; date of approval: 22/11/2022). Prospective consent will be obtained and the study will be conducted in accordance with the Declaration of Helsinki. The finalised manuscript, including aggregate data, will be submitted for publication in a peer reviewed journal. ADAPT-TDM will determine whether beta-lactam TDM-guided dose adaptation is reproducible and feasible and provide important information required to implement this intervention in a phase III trial.
BACKGROUND: Australian New Zealand Clinical Trials Registry, ACTRN12623000032651.
METHODS: A beta-lactam antibiotic Dose AdaPtation feasibility randomised controlled Trial using Therapeutic Drug Monitoring (ADAPT-TDM) is a single-centre, unblinded, feasibility randomised controlled trial aiming to enroll up to 60 critically ill adult participants (≥18 years). TDM and dose adjustment will be performed daily in the intervention group; the standard of care group will undergo plasma sampling, but no dose adjustment. The main outcomes include: (1) feasibility of recruitment, defined as the number of participants who are recruited from a pool of eligible participants, and (2) fidelity of TDM, defined as the degree to which TDM as a test is delivered as intended, from accurate sample collection, sample processing to result availability. Secondary outcomes include target attainment, uptake of TDM-guided dosing and incidence of neurotoxicity, hepatotoxicity and nephrotoxicity.
BACKGROUND: This study has been approved by the Alfred Hospital human research ethics committee, Office of Ethics and Research Governance (reference: Project No. 565/22; date of approval: 22/11/2022). Prospective consent will be obtained and the study will be conducted in accordance with the Declaration of Helsinki. The finalised manuscript, including aggregate data, will be submitted for publication in a peer reviewed journal. ADAPT-TDM will determine whether beta-lactam TDM-guided dose adaptation is reproducible and feasible and provide important information required to implement this intervention in a phase III trial.
BACKGROUND: Australian New Zealand Clinical Trials Registry, ACTRN12623000032651.
摘要：
背景：由于生理改变对药代动力学的影响，危重病患者存在不良β-内酰胺抗生素（β-内酰胺）暴露的风险。次优浓度可导致治疗失败或毒性。治疗药物监测（TDM）涉及根据测得的血浆浓度调整剂量和个性化给药，以提高改善暴露的可能性。尽管有潜在的好处,它的采用一直很缓慢，和实施数据，剂量适应性和安全性很少。该试验的目的是评估在重症监护病房中实施β-内酰胺TDM指导给药的可行性和保真度。
方法：使用治疗药物监测（ADAPT-TDM）的β-内酰胺抗生素剂量AdaPtation可行性随机对照试验是单中心，未失明,可行性随机对照试验旨在纳入多达60名危重成人参与者(≥18岁).干预组每天进行TDM和剂量调整；标准护理组将进行血浆采样，但没有剂量调整。主要成果包括:(1)招聘的可行性，定义为从合格参与者池中招募的参与者数量，和(2)TDM的保真度，定义为TDM作为测试按预期交付的程度，从准确的样本收集中，样品处理到结果可用性。次要成果包括实现目标，TDM指导给药的摄取和神经毒性的发生率，肝毒性和肾毒性。
背景：这项研究已获得阿尔弗雷德医院人类研究伦理委员会的批准，道德与研究治理办公室(参考：项目编号565/22；批准日期：22/11/2022）。将获得预期的同意，并根据赫尔辛基宣言进行研究。最终的手稿，包括聚合数据，将提交在同行评审的期刊上发表。ADAPT-TDM将确定β-内酰胺TDM指导的剂量适应是否可重复和可行，并提供在III期试验中实施该干预所需的重要信息。
背景：澳大利亚新西兰临床试验注册中心，ACTRN12623000032651。
方法：使用治疗药物监测（ADAPT-TDM）的β-内酰胺抗生素剂量AdaPtation可行性随机对照试验是单中心，未失明,可行性随机对照试验旨在纳入多达60名危重成人参与者(≥18岁).干预组每天进行TDM和剂量调整；标准护理组将进行血浆采样，但没有剂量调整。主要成果包括:(1)招聘的可行性，定义为从合格参与者池中招募的参与者数量，和(2)TDM的保真度，定义为TDM作为测试按预期交付的程度，从准确的样本收集中，样品处理到结果可用性。次要成果包括实现目标，TDM指导给药的摄取和神经毒性的发生率，肝毒性和肾毒性。
背景：这项研究已获得阿尔弗雷德医院人类研究伦理委员会的批准，道德与研究治理办公室(参考：项目编号565/22；批准日期：22/11/2022）。将获得预期的同意，并根据赫尔辛基宣言进行研究。最终的手稿，包括聚合数据，将提交在同行评审的期刊上发表。ADAPT-TDM将确定β-内酰胺TDM指导的剂量适应是否可重复和可行，并提供在III期试验中实施该干预所需的重要信息。
背景：澳大利亚新西兰临床试验注册中心，ACTRN12623000032651。
