CTRI

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CTRI Number

CTRI/2026/03/106416 [Registered on: 17/03/2026] Trial Registered Prospectively

Last Modified On:

16/03/2026

Post Graduate Thesis

Yes

Type of Trial

Observational

Type of Study

Follow Up Study

Study Design

Single Arm Study

Public Title of Study

Vancomycin Behavior in the Body of Critically Ill ICU Patients.

Scientific Title of Study

Population Pharmacokinetic Modeling with Inflammatory Covariate Analysis and Neural Network Predictive Modeling of Vancomycin Disposition in Adult ICU Patients: Prospective Observational Clinical Pharmacokinetic Study

Trial Acronym

NIL

Secondary IDs if Any

Secondary ID	Identifier
NIL	NIL

Details of Principal Investigator or overall Trial Coordinator (multi-center study)

Name	Anand Srinivasan
Designation	Additional Professor
Affiliation	AIIMS Bhubaneswar
Address	Department of Pharmacology, AIIMS Bhubaneswar, Odisha, India. Khordha ORISSA 751019 India
Phone	9216996577
Fax
Email	anandsrinivasan@aiimsbhubaneswar.edu.in

Details of Contact Person
Scientific Query

Name	Anand Srinivasan
Designation	Additional Professor
Affiliation	AIIMS Bhubaneswar
Address	Department of Pharmacology, AIIMS Bhubaneswar, Odisha, India. Khordha ORISSA 751019 India
Phone	9216996577
Fax
Email	anandsrinivasan@aiimsbhubaneswar.edu.in

Details of Contact Person
Public Query

Name	Anand Srinivasan
Designation	Additional Professor
Affiliation	AIIMS Bhubaneswar
Address	Department of Pharmacology, AIIMS Bhubaneswar, Odisha, India. ORISSA 751019 India
Phone	9216996577
Fax
Email	anandsrinivasan@aiimsbhubaneswar.edu.in

Source of Monetary or Material Support

NIL

Primary Sponsor

Name	AIIMS Bhubaneswar
Address	AIIMS Bhubaneswar,Sijua, Patrapada, Bhubaneswar, Odisha 751019
Type of Sponsor	Government medical college

Details of Secondary Sponsor

Name	Address
NIL	NIL

Countries of Recruitment

India

Sites of Study

No of Sites = 1
Name of Principal Investigator	Name of Site	Site Address	Phone/Fax/Email
Anand Srinivasan	All India Institute of Medical Sciences, Bhubaneswar	Sijua, Patrapada, Bhubaneswar, Odisha 751019 Khordha ORISSA	9216996577 anandsrinivasan@aiimsbhubaneswar.edu.in

Details of Ethics Committee

No of Ethics Committees= 1
Name of Committee	Approval Status
Institutional Ethics Committee For Student Research, AIIMS Bhubaneswar	Approved

Regulatory Clearance Status from DCGI

Status

Not Applicable

Health Condition / Problems Studied

Health Type	Condition
Patients	(1) ICD-10 Condition: A419\|\|Sepsis, unspecified organism, (2) ICD-10 Condition: A490\|\|Staphylococcal infection, unspecified site,

Intervention / Comparator Agent

Type	Name	Details
Intervention	Vancomycin	Intravenous Vancomycin administered as per standard ICU protocol. Loading Dose: 25 to 30 mg per kg Total Body Weight (maximum 3000 mg) infused over 2 to 4 hours. Maintenance Dose: 15 to 20 mg per kg every 8 to 12 hours, infused over a minimum of 60 minutes per gram. Dose adjustments made based on renal function, therapeutic drug monitoring, and clinical condition as per treating physicians discretion. Blood samples for pharmacokinetic analysis collected at 8 pre-specified time points: - Day 1 (5 samples): 0.5h mid-infusion, 1h end of infusion, 2h post-infusion, 6h late distribution, 12h pre-maintenance trough. - Day 2 (3 samples): 24h steady-state trough, 25h steady-state peak, 30h mid-interval. Total blood volume collected: approximately 8 mL over 48 hours. Vancomycin concentrations measured using Roche ONLINE TDM Vancomycin Gen.3 assay on Roche Cobas Integra 400 Plus analyzer. No experimental drug is used. This is an observational pharmacokinetic study only.

Inclusion Criteria

Age From	18.00 Year(s)
Age To	99.00 Year(s)
Gender	Both
Details	1. Adult patients aged 18 years or above admitted to medical or central ICU receiving intravenous vancomycin for suspected or documented Gram-positive infection. 2. Minimum anticipated duration of vancomycin therapy of 48 hours or more. 3. Written informed consent obtained from patient or legally authorized representative.

ExclusionCriteria

Details

1. Pregnant patients.
2. Patients with burns involving more than 20 percent of Body Surface Area (BSA).
3. Patients on Extracorporeal Membrane Oxygenation (ECMO).
4. Patients with known anaphylaxis to vancomycin.
5. Patients requiring renal replacement therapy or dialysis.

Method of Generating Random Sequence

Not Applicable

Method of Concealment

Not Applicable

Blinding/Masking

Not Applicable

Primary Outcome

Outcome

TimePoints

Development and validation of a two-compartment population
pharmacokinetic (PopPK) model for vancomycin in adult ICU patients
incorporating inflammatory markers as covariates.

Primary pharmacokinetic parameters to be estimated:
1. Vancomycin Clearance (CL) in L/h
2. Central Volume of Distribution (Vc) in L
3. Peripheral Volume of Distribution (Vp) in L
4. Intercompartmental Clearance (Q) in L/h
5. Area Under the Concentration-Time Curve over 24 hours (AUC24)
in mg.h/L

Inflammatory covariates to be evaluated: C-reactive protein (CRP),
Interleukin-6 (IL-6), Procalcitonin, and Fibrinogen.

Pharmacokinetic sampling performed over the first 48 hours of
vancomycin therapy.

Day 1: 0.5 hours (mid-infusion), 1 hour (end of infusion),
2 hours (post-infusion), 6 hours (late distribution phase),
12 hours (pre-maintenance trough).

Day 2: 24 hours (steady-state trough), 25 hours (steady-state peak),
30 hours (mid-interval).

Final outcome assessment at end of vancomycin therapy
(up to 7 days).

Secondary Outcome

Outcome	TimePoints
Comparison of predictive performance of Physics-Informed Neural Networks (PINNs) and other neural network architectures against traditional population pharmacokinetic (PopPK) model for vancomycin trough concentration and AUC24 estimation in adult ICU patients. Performance metrics: Mean Absolute Error (MAE), Root Mean Squared Error (RMSE), R-squared, and percentage of predictions within plus or minus 20 to 30 percent of observed values.	Model training and validation performed on pharmacokinetic data collected over first 48 hours (Day 1 and Day 2 sampling). Final model comparison performed at end of study (Month 18 to 24).
Probability of target attainment (PTA) for vancomycin AUC24/MIC ratio of 400 to 600 mg.h/L assessed using Monte Carlo simulations (n=5000). Development of ICU-specific dosing nomograms tailored to renal function (eGFR) and inflammatory status (CRP, IL-6).	Monte Carlo simulations performed after final PopPK model validation. Nomograms developed during analysis phase (Month 13 to 18). Target attainment evaluated based on PK data from Days 1 to 7 of vancomycin therapy.
Assessment of vancomycin-associated nephrotoxicity as a safety outcome, defined as acute kidney injury (AKI) of KDIGO stage 1 or above, occurring within 7 days of vancomycin initiation. Monitored by serial serum creatinine and eGFR measurements at baseline (Day 0), Day 4, Day 5, and Day 7.	Baseline (Day 0): Pre-vancomycin serum creatinine and eGFR. Day 4 and Day 5: Serial renal function monitoring. Day 7: Final renal function assessment (if therapy extended). End of therapy: Final safety outcome recorded.
Comparative evaluation of predictive performance of one-compartment versus two-compartment pharmacokinetic models for vancomycin using objective function value (OFV), goodness-of-fit diagnostics, visual predictive checks (VPC), normalised prediction distribution errors (NPDE), and bootstrap confidence intervals.	Model building and comparison performed during analysis phase after completion of data collection (Month 13 to 18). Based on pharmacokinetic data collected on Day 1 and Day 2 of vancomycin therapy.

Target Sample Size

Total Sample Size="35"
Sample Size from India="35"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"

Phase of Trial

N/A

Date of First Enrollment (India)

01/04/2026

Date of Study Completion (India)

Applicable only for Completed/Terminated trials

Date of First Enrollment (Global)

Date Missing

Date of Study Completion (Global)

Applicable only for Completed/Terminated trials

Estimated Duration of Trial

Years="2"
Months="0"
Days="0"

Recruitment Status of Trial (Global)

Not Applicable

Recruitment Status of Trial (India)

Not Yet Recruiting

Publication Details

N/A

Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?

Response - NO

Brief Summary

Vancomycin is a commonly used antibiotic for treating serious bacterial infections in critically ill patients admitted to the Intensive Care Unit (ICU). Giving the right dose of vancomycin is challenging in ICU patients because their body conditions change rapidly due to factors such as altered kidney function, fluid shifts, and inflammation, all of which affect how the drug moves through the body.

This prospective observational study aims to enroll 35 adult ICU patients at AIIMS Bhubaneswar who are receiving standard intravenous vancomycin therapy for suspected or documented Gram-positive infections. Blood samples will be collected at 8 pre-specified time points over the first 48 hours of therapy to measure vancomycin concentrations. Routine inflammatory markers already collected as part of ICU care such as C-reactive protein (CRP), Interleukin-6 (IL-6), and Procalcitonin will be recorded and included in the analysis.

Using these data, a two-compartment population pharmacokinetic (PopPK) model will be developed using nonlinear mixed-effects modeling (nlmixr2 in R) to describe how vancomycin is distributed and cleared from the body, and to identify which patient factors, especially inflammation-related markers, most influence vancomycin drug levels. The study will also compare this traditional PopPK model against an Artificial Intelligence-based approach called Physics-Informed Neural Networks (PINNs) to determine which method better predicts vancomycin concentrations and drug exposure targets.

Computer simulations will be performed to assess the probability of achieving therapeutic targets and to develop ICU-specific dosing guidance charts tailored to a patient’s kidney function and inflammatory status. Vancomycin-associated kidney injury will be monitored as a safety outcome.

No new or experimental drug is being tested. Vancomycin is administered as per standard ICU protocol. This study is purely observational and is intended to improve the precision and safety of vancomycin dosing in critically ill patients in India.