Model-Informed Precision Dosing on Amikacin and Vancomycin Therapy in Critically Ill Children

Model-Informed Precision Dosing on Amikacin and Vancomycin Therapy in Critically Ill Children: A Pilot Randomized Clinical Trial

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.

Study Overview

• Status: Completed
• Conditions: Model Informed Precision Dosing
• Intervention / Treatment: Device: MIPD Tool

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06100
    • Hacettepe University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Hospitalized patients (NICU) receiving vancomycin or amikacin
• Treatment with vancomycin or amikacin initiated during hospitalization
• At least one therapeutic drug monitoring (TDM) measurement obtained Exclusion Criteria
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of Care Group
Experimental: MIPD Group	Device: MIPD Tool; It is a precision dosing platform that combines population pharmacokinetic/pharmacodynamic (popPK/PD) modeling with artificial intelligence and machine learning to optimize individualized drug therapy. It uses patient-specific demographic, clinical, and laboratory data to generate real-time personalized dosing recommendations based on validated popPK models.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive Accuracy of Model-Informed Precision Dosing (MIPD) Based on Median Absolute Error (MdAE)	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.	From first therapeutic drug monitoring (TDM) sample to second TDM sample (typically within 3-5 days of therapy)
Predictive Accuracy of Model-Informed Precision Dosing (MIPD) Based on Mean Absolute Error (MAE)	Mean Absolute Error (MAE) between model-predicted and observed serum antibiotic concentrations will be calculated to assess overall prediction error.	From first therapeutic drug monitoring (TDM) sample to second TDM sample (typically within 3-5 days of therapy)
Predictive Accuracy of Model-Informed Precision Dosing (MIPD) Based on Median Error (MdE)	Median Error (MdE) will be calculated to evaluate directional bias between predicted and observed serum antibiotic concentrations.	From first therapeutic drug monitoring (TDM) sample to second TDM sample (typically within 3-5 days of therapy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in C-Reactive Protein (CRP) Level	The absolute change in serum C-reactive protein (CRP) level from baseline (within 24 hours of antibiotic initiation) to the time of the second TDM sample will be evaluated as an inflammatory response marker.	Baseline to approximately day 3-5 of therapy
Change in Procalcitonin Level	The absolute change in serum procalcitonin level from baseline to the time of the second TDM sample will be assessed.	Baseline to approximately day 3-5 of therapy
Change in Serum Creatinine Level	The absolute change in serum creatinine level from baseline to the time of the second TDM sample will be evaluated as a marker of renal safety.	Baseline to approximately day 3-5 of therapy
Change in Pharmacokinetic Model-Fit Category	Within-patient change in pharmacokinetic model-fit category (poor, intermediate, good) between the first and second TDM measurements will be assessed to evaluate improvement in model performance after Bayesian updating.	From first to second TDM sample (typically within 3-5 days)

Collaborators and Investigators

• Sponsor: Hacettepe University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Actual): August 30, 2025
• Study Completion (Actual): October 27, 2025

Study Registration Dates

• First Submitted: November 28, 2025
• First Submitted That Met QC Criteria: December 23, 2025
• First Posted (Estimated): January 2, 2026

Study Record Updates

• Last Update Posted (Estimated): January 2, 2026
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: Neo-MIPD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No