Pharmacokinetics of Colistin in Critically Ill Patients With Extracorporeal Membrane Oxygenation
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Verification of the ECMO-induced changes of colistin or CMS area under the plasma concentration versus time curve (AUC) in critically ill patients.
研究概览
简要总结
Colistin is a lipopeptide antibiotic administered as an inactive prodrug - colistin methanesulfonate (CMS). Colistin is a drug with a narrow therapeutic window; the limiting factors are mainly nephrotoxicity and neurotoxicity dependent on plasma concentrations. The number of patients with these types of infections, as well as the number of patients requiring extracorporeal membrane oxygenation (ECMO) support for severe respiratory failure, increased significantly in association with COVID-19-induced infections. ECMO can generally affect the pharmacokinetics of drugs by creating a new compartment.
详细描述
The COL-ECMO2022 study is a prospective, non-randomized, open-label single-center, phase IV clinical trial that is designed to assess the influence of ECMO on the pharmacokinetics of colistin and CMS. The study is planned to include up to 30 patients with indication of colistin who will be assigned to one of two arms in a 1:1 ratio depending on the presence/absence of ECMO. All study participants will receive colistin standard, approved dose schedule intravenously. The plasma concentrations of colistin and CMS took at defined intervals will be assessed by high-performance liquid chromatography-mass spectrometry. Patients will participate in the clinical trial for a maximum of three monitored dosing intervals.
Discussion: This study is expected to provide essential evidence-based data on the impact of ECMO on colistin pharmacokinetics in critically ill patients as well as to shed some light on how to optimize the colistin dosing for critically ill patients on ECMO by designing the population model.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Men and women (with a negative pregnancy test prior to study enrolment in women of childbearing potential)
- •Hospitalized at the Department of Anaesthesiology and Resuscitation, St. Anne´s University Hospital Brno
- •Indication for parenteral colistin (or CMS) as part of standard medical care, i.e., in patients with severe bacterial infection
- •Informed consent given. In unconscious patients, the study investigator will decide whether to include the patient in the study; this decision is made whenever possible in a medical council consisting of at least one independent physician informed about the study details and one study investigator. An interim informed consent will be given after considering all individual risks. In this case, the Ethics Committee of St. Anne's Hospital in Brno will be informed of the patient's inclusion. The investigator will ask study participants in whom good quality consciousness is restored to give subsequent informed consent without unreasonable delay.
- •Additional inclusion criterion:
- •For some patients (15 individuals are expected), in addition to all the criteria listed in the Eligibility Criteria section, the following inclusion criterion is provided:
- •ECMO support is needed as part of standard therapy for severe respiratory failure.
排除标准
- •Pregnancy,
- •Breast-feeding,
- •Refusal to give the informed consent (primarily or after regaining consciousness).
研究组 & 干预措施
Critically ill patients with ECMO
The subjects connected to ECMO will be treated with colistin ain approved dosing - a loading dose of 9 MIU intravenously over 30 minutes followed after 12 hours by a maintenance dose of 4,5 MIU intravenously over 30 minutes every 12 hours. Only in patients requiring continuous renal replacement methods will the interval of the maintenance doses be 8 hours.
干预措施: Colistin (Drug)
Critically ill patients without ECMO
The subjects not connected to ECMO will be treated with colistin ain approved dosing - a loading dose of 9 MIU intravenously over 30 minutes followed after 12 hours by a maintenance dose of 4,5 MIU intravenously over 30 minutes every 12 hours. Only in patients requiring continuous renal replacement methods will the interval of the maintenance doses be 8 hours.
干预措施: Colistin (Drug)
结局指标
主要结局
Verification of the ECMO-induced changes of colistin or CMS area under the plasma concentration versus time curve (AUC) in critically ill patients.
时间窗: 24 hours
The primary objective of the clinical trial is to determine the area under the plasma concentration versus time curve of colistin and CMS in critically ill patients with and without ECMO during the dosing interval, calculate and compare the area under the plasma concentration versus time curve of CMS and colistin in each group.
次要结局
- Model of population pharmacokinetics of colistin in critically ill patients - Cmax(2 hours after colistin administration. The model will be designed through study completion, an average of 1 year)
- Model of population pharmacokinetics of colistin in critically ill patients - Cmin(12 hours after colistin administration. The model will be designed through study completion, an average of 1 year)
- Model of population pharmacokinetics of colistin in critically ill patients - AUC(24 hours after colistin administration. The model will be designed through study completion, an average of 1 year)
- Model of population pharmacokinetics of colistin in critically ill patients - Tminc(12 hours after colistin administration. The model will be designed through study completion, an average of 1 year)
- Model of population pharmacokinetics of colistin in critically ill patients - Tmaxc(2 hours after colistin administration. The model will be designed through study completion, an average of 1 year)