Pharmacokinetics of Micafungin in Patients of Intensive Care Units
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- To describe micafungin concentrations over time,
研究概览
简要总结
Invasive fungal infections (IFIs) are a frequent cause of morbidity and mortality in high-risk patients, such as immunocompromised patients. Candida is currently the predominant fungal pathogen in these patient populations and is associated with significant morbidity and a high mortality.
Micafungin (MCF) is a semisynthetic compound belonging to the new class of antifungal agents, the echinocandin lipopeptides, that has potent in vitro and experimental in vivo activity against a variety of pathogenic Candida species and Aspergillus species. Its applied indications are so the treatment and/or the prophylaxis of Candida and Aspergillus infections. MCF is currently licensed for the treatment of candidiasis at doses of either 100 or 150 mg a day.
The efficacy of MCF is linked to the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC0-24/ MIC ratio).
On one hand:
- It was demonstrated that 98% of invasive candidiasis patients with a MCF AUC/MIC ratio between 3 and 12 achieve microbiological clearance, as opposed to only 85% of those with an AUC/MIC ratio < 3. In the case of infections by Candida parapsilosis, which exhibits drug MICs that are 50- to100-fold higher, 100% of patients with an AUC/MIC ratio >285 achieve microbiological clearance, as opposed to 82% of those below that exposure level.(1)
On the other hand:
- It is well known that patients of intensive care units (ICU) are characterized by particular pharmacokinetic parameters with higher apparent volume of distribution (VC/F) and/or higher apparent systemic clearance (CL/F). In a population of healthy volunteers, it was observed that CL/F of MCF presents a high interpatient variability.(2)
- Whether most ICUs patients achieve optimal AUC/MIC ratio thresholds at standard doses has not been investigated so far. In particular, lower AUCs might be reached in patients having the highest VC/F values. Such patients would then be at risk of therapy failure and would benefit from individualized-dosing strategies.
In this context, the study of the pharmacokinetics of MCF in critically ill patients seems to be necessary.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
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
- •Critically ill patients hospitalized in an ICU, with suspected or proven invasive fungal infections, for whom the decision has been made to start a treatment based on MCF.
- •Age > 18 years.
- •Patients willing to give their written informed consent for their participation to the study.
- •Patients affiliated to the French social security system or equivalent.
排除标准
- •Patient for whom a treatment based on MCF has already been started
- •Patient who have benefited from bone marrow transplantation
- •Age < 18 years
- •Patient under legal protection
- •Patient deprived of liberty
- •Pregnant or breast-feeding woman or woman of childbearing potential without efficient contraception (based on declaration)
- •Patient with any altered mental status or any psychiatric condition that would interfere with the understanding of the study
- •Patient enrolled in another clinical trial testing drugs or therapeutic strategies (including the so-called "exclusion period")
研究组 & 干预措施
Pharmacokinetics of micafungin
干预措施: micafungin (Other)
结局指标
主要结局
To describe micafungin concentrations over time,
时间窗: 3 weeks
The evaluation of the PK model performance will be based on its ability: * To describe micafungin concentrations over time, * To explain the sources of inter-individual PK variability. It will be done by the calculation of the bias between concentrations predicted using the model and observed concentrations.
次要结局
- To estimate the proportion of patients hospitalized in an ICU achieving the target AUC or AUC/MIC when receiving the recommended regimen(3 weeks)