Population Pharmacokinetics of Amikacin in Suspected Cases of Neonatal Sepsis: Multicenter Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 138
- 试验地点
- 1
- 主要终点
- PK/PD targets of amikacin
研究概览
简要总结
Aminoglycosides such as Amikacin are routinely used in newborns for the treatment of neonatal sepsis due to gram-negative bacilli. Despite the frequency of this indication, it has not yet been possible to establish definitive dosage schedules that ensure effectiveness and low risk of toxicity, due to the high pharmacokinetic variability observed in this population.
In addition to anthropometric variables, evidence from retrospective studies suggests that sepsis could be capable of significantly modifying the pharmacokinetics of aminoglycosides in neonates, but the investigators suggest conducting prospective studies of higher methodological quality to verify this hypothesis.
Due to the lack of pharmacokinetic and pharmacodynamic (PK / PD) studies of Amikacin in this group of patients, the investigators have raised the need to develop a prospective observational study; describing a PK / PD model of amikacin in newborns with suspected sepsis.
详细描述
Three blood samples will be taken from each of the 138 participants. As a standard of care, a sample will always be taken at 0.5h (Cmax) after the first dose and a sample before the second dose, which can be at 24h, 36h, or 48h as per physician indication. The third sample will be collected according to what has been assigned by a block randomization method, in one of the following moments: 1, 2, 4, 8, 12 or 18 hours after the administration of the first dose of Amikacin.
The methods used to analyze the samples will be: Particle Enhanced Turbidimetric Immunoassay (PETIA), Architect C8000; and Homogeneous Microparticle Immunoassay in Solution (KIMS), Roche systems. The determination of the susceptibility and minimum Inhibitory Concentration (MIC) will be carried out by the laboratories of each hospital by agar dilution method.
PK/PD profile of amikacin will be evaluated with NONMEM (non-linear mixed effects modelling) software for the analysis.
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
- 3 Days 至 1 Month（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Receive at least one dose of Amikacin
- •Be at least three days old (72 hours)
排除标准
- •Receive the first dose of Amikacin in a healthcare center other than those included in the research
- •Patient on renal replacement therapy
研究组 & 干预措施
No Sepsis / Sepsis
To compare amikacin PK / PD models of newborns with a confirmed diagnosis of sepsis (clinical or microbiological) and with ruled out sepsis.
干预措施: Amikacin Sulfate Injection (Drug)
结局指标
主要结局
PK/PD targets of amikacin
时间窗: first dose amikacin (1 day)
Peak Plasma Concentration (Cmax) over 8 fold Minimum Inhibitory Concentration (MIC) or Cmax: 24-35 mg/L
Clearance (L/h) of Amikacin
时间窗: first dose amikacin (1 day)
The mean population parameter and their interindividual variability in neonates with suspected sepsis
Volume of Distribution (L/Kg) of Amikacin
时间窗: first dose amikacin (1 day)
The mean population parameter and their interindividual variability in neonates with suspected sepsis
次要结局
未报告次要终点