Impact of a Loading Dose of Caspofungin on Pharmacokinetic and Pharmacodynamic Parameters Target Achievements for Severe Candida Infections in ICU Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Outcome Rea
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Area Under the inhibitory curve (AUIC)
研究概览
简要总结
Echinocandins are the drug of choice in severe candida infections. Efficacy of echinocandins is related to concentration and area under the curve (AUC) of the drug.
Available pharmacokinetic studies found that concentration of echinocandins mainly caspofungin is sub-optimal in severe candida infections in intensive care unit (ICU) patients.
Higher dose of caspofungin has been proven to be safe in critically ill patients but its impact on the ability to reach PK/PD target is unknown.
The aim of this study is to evaluate the impact of a loading dose of caspofungin on PK/PD parameters within the first 24-hours.
详细描述
Invasive fungal infections are associated to a high mortality rate in ICU, partly because of a delayed treatment.
PK/PD targets for caspofungin are the peak concentration over minimal inhibitory concentration (MIC) ratio which should reach 10 and the area under the inhibitory curve (AUIC) which should be over 200. High distribution volume in ICU patients and increase of MICs due to extensive use of antifungal agents make optimal concentration difficult to obtain. High doses up to 150mg of caspofungin have been reported to be safe. Thus, in our unit, a loading dose of 140mg of caspofungin is a standard practice but was never rigorously evaluated.
The aim of the present study is to measure the impact of a loading dose of 140mg of caspofungin on the pharmacokinetic parameters in the first 24 hours of treatment.
The AUIC and maximal concentration (CMax) / (MIC) according to the recovered yeasts will be measured. The investigators also planned a Monte-Carlo simulation using MICs obtained from clinically relevant candida strains isolated in Bichat and Grenoble hospitals in order to evaluate the percentage of patients appropriately treated within the first 24 hours according to Candida species and previous use of antifungals.
Recovered strains from epidemiological studies will be used for PKPD modelling and will use s. A second Monte-Carlo simulation will be done using data from the Amarcand 2 study.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient hospitalized in intensive care
- •Age> 18 years
- •Patient with a central catheter
- •Patient with invasive mechanical ventilation
- •Patient receiving more than 0.1 mcg / kg / min of adrenaline or noradrenaline
- •Patient treated for proven (positive blood cultures or positive specimen obtained during a surgical or percutaneous puncture) or suspected (risk factor, extra digestive colonization, absence of other uncontrolled bacterial infections, candida score> 3) invasive candidiasis.
- •Patient affiliated to medical insurance
排除标准
- •Expected length of stay under 48H
- •Age <18 years
- •Pregnant or breastfeeding women
- •Limited or sustained life support therapy
- •Patient unable to legally consent
- •History of Allergy, hypersensitivity or intolerance to echinocandins or Drug excipients
结局指标
主要结局
Area Under the inhibitory curve (AUIC)
时间窗: 24 hours after the loading dose
Six samples (before infusion; 2, 3, 5, 7 and 24 hours after infusion) will be obtained between inclusion and 24 hours to calculate the area under the curve. MIC will be determined with E-test technique.
次要结局
- Peak concentration over MIC (Cmax/MIC)(2 hours avec the loading dose)