Model-Informed Precision Dosing on Amikacin and Vancomycin Therapy in Critically Ill Children: A Pilot Randomized Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Predictive Accuracy of Model-Informed Precision Dosing (MIPD) Based on Median Absolute Error (MdAE)
研究概览
简要总结
Achieving optimal antibiotic exposure in critically ill pediatric patients is difficult due to (their) dynamic physiology and variability. Conventional weight-based regimens often fail to reach pharmacokinetic/pharmacodynamic (PK/PD) targets for narrow therapeutic index agents such as vancomycin and amikacin. Model-Informed Precision Dosing (MIPD), which integrates Bayesian forecasting with population pharmacokinetics (popPK), offers a potentially valuable yet underexplored approach in pediatric intensive care to better attain and sustain target exposure. This pilot randomized clinical trial evaluated MIPD-guided dosing of vancomycin and amikacin using InsightRX Nova® versus standard of care (SoC) in a tertiary PICU. Patients whose model-recommended doses matched standard regimens were analyzed under SoC. Primary outcomes included prediction accuracy (a priori vs a posteriori) and model fit; secondary outcomes assessed dose optimization, inflammatory response, renal safety, treatment duration, and mortality.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 38 Months 至 81 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hospitalized patients (NICU) receiving vancomycin or amikacin
- •Treatment with vancomycin or amikacin initiated during hospitalization
- •At least one therapeutic drug monitoring (TDM) measurement obtained
排除标准
- •Failure to obtain written informed consent
- •Death within the first 24 hours after treatment initiation
- •Discontinuation of therapy before the first TDM measurement
- •Determined unsuitable for study participation by the treating physician
结局指标
主要结局
Predictive Accuracy of Model-Informed Precision Dosing (MIPD) Based on Median Absolute Error (MdAE)
时间窗: From first therapeutic drug monitoring (TDM) sample to second TDM sample (typically within 3-5 days of therapy)
Predictive accuracy of the pharmacokinetic model will be evaluated by calculating the Median Absolute Error (MdAE) between model-predicted and observed antibiotic serum concentrations. MdAE was prespecified as the primary accuracy metric due to its robustness to outliers in small pediatric samples.
Predictive Accuracy of Model-Informed Precision Dosing (MIPD) Based on Mean Absolute Error (MAE)
时间窗: From first therapeutic drug monitoring (TDM) sample to second TDM sample (typically within 3-5 days of therapy)
Mean Absolute Error (MAE) between model-predicted and observed serum antibiotic concentrations will be calculated to assess overall prediction error.
Predictive Accuracy of Model-Informed Precision Dosing (MIPD) Based on Median Error (MdE)
时间窗: From first therapeutic drug monitoring (TDM) sample to second TDM sample (typically within 3-5 days of therapy)
Median Error (MdE) will be calculated to evaluate directional bias between predicted and observed serum antibiotic concentrations.
次要结局
- Change in C-Reactive Protein (CRP) Level(Baseline to approximately day 3-5 of therapy)
- Change in Procalcitonin Level(Baseline to approximately day 3-5 of therapy)
- Change in Serum Creatinine Level(Baseline to approximately day 3-5 of therapy)
- Change in Pharmacokinetic Model-Fit Category(From first to second TDM sample (typically within 3-5 days))
研究者
Nadir Yalçın
Director
Hacettepe University