Vancomycin and Acute Kidney Injury in Sepsis Treatment - Intervention (VAST-i)

Vancomycin and Acute Kidney Injury in Sepsis Treatment - Pharmacologic Modeling Intervention

The goal of this clinical trial is to determine if vancomycin dosing in children with sepsis can be improved by using updated, personalized dosing models that account for new markers of an individual's kidney function. Vancomycin is prescribed based on the known information of how the body breaks this medicine down. Vancomycin may not be effective if blood levels of the medicine are too low. Vancomycin has potential side effects, including the possibility of injury to the kidney. These side effects usually happen when blood levels of vancomycin are too high. There are guidelines for the range of vancomycin blood levels doctors should target to treat an infection and lower the risk of side effects. Children with sepsis may metabolize vancomycin at different rates, faster or slower, than children who do not have sepsis. For these reasons, the current dosing strategy may lead to a higher risk of kidney injury or a risk of not adequately treating an infection in children with sepsis. The investigators' goal is to use new vancomycin dosing equations to improve the ability to select the right dose of vancomycin. The main questions this trial aims to answer are:

1. Is it feasible to use personalized models of vancomycin dosing in children with sepsis?
2. Will personalized models of vancomycin dosing achieve vancomycin blood levels in acceptable ranges?

Study Overview

• Status: Recruiting
• Conditions: Sepsis
• Intervention / Treatment: Other: personalized dosing adjustment of vancomycin

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Julie Fitzgerald, MD PhD; Phone Number: 215-590-4879; Email: fitzgeraldj@chop.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Contact: Alanah McKelvey; Phone Number: 215-590-1000; Email: mckelveya@chop.edu
      • Principal Investigator: Julie Fitzgerald, MD PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age >1 month and <18 years
2. Weight >5kg and <50kg
3. Vancomycin intended duration of therapy ≥48 hours
4. Admitted to intensive care unit with suspected or confirmed sepsis
5. Either sepsis-induced respiratory (invasive mechanical ventilation) or cardiovascular (vasoactive infusion) dysfunction as part of sepsis-associated organ dysfunction (these organ dysfunctions may be improving or resolved at the time of enrollment)

Exclusion Criteria:

1. Serum creatinine elevated and meets criteria for trough-based dosing by local Clinical Pharmacy
2. Methicillin resistant Staph aureus minimum inhibitory concentration (MIC)>1
3. Central nervous system infection
4. Extracorporeal support (extracorporeal membrane oxygenation, continuous renal replacement therapy)
5. Pregnancy
6. Patients on chronic dialysis therapy
7. Patients with known history of delayed vancomycin clearance based on local pharmacy records

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Personalized vancomycin Pharmacokinetic model for dose adjustments; Enrolled patients who are prescribed vancomycin by the clinical team will transition to the study-determined empiric vancomycin dosing at the time of enrollment, 12mg/kg/dose administered as an extended intravenous (IV) infusion over 2 hours given every 6 hours. Urinary neutrophil gelatinase-associated lipocalin (NGAL) will be measured as soon as possible after enrollment. Dosage adjustments will be made using the personalized vancomycin pharmacokinetic (PK) model incorporating the NGAL level once resulted. Daily urinary NGAL will be measured while on vancomycin therapy and in the intensive care unit (ICU) to evaluate for ongoing changes in renal function that may necessitate further dosage adjustments using the personalized vancomycin PK model, until clinically stabilized. Patients will undergo vancomycin area under the curve (AUC) monitoring with three timed blood draws for vancomycin concentrations with each vancomycin dosing change with a goal AUC target range of 400-600.

Other: personalized dosing adjustment of vancomycin; A personalized vancomycin PK model that incorporates kidney injury biomarkers will be used for vancomycin dose adjustments to achieve goal AUC levels.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility - personalized dose adjustment performed	Percentage of enrolled patients in which urinary neutrophil gelatinase-associated lipocalin is measured and used to make a vancomycin dosing recommendation	From enrollment to the longer of 7 days after the completion of vancomycin therapy or through 30 days from enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility - Use of study-determined empiric vancomycin dosing	Percentage of patients transitioned to the study-determined empiric vancomycin dosing.	From enrollment to the longer of 7 days after the completion of vancomycin therapy or through 30 days from enrollment
Feasibility - Area under the curve sampling attainment on study empiric vancomycin dosing	Percentage of patients transitioned to the study-determined empiric vancomycin dosing and undergo subsequent area under the curve sampling.	From study enrollment to the longer of 7 days after the completion of vancomycin therapy or through 30 days from enrollment
Feasibility - Dosing change based on urinary neutrophil gelatinase-associated lipocalin level	Percentage of patients enrolled in which urinary neutrophil gelatinase-associated lipocalin is used to make a dosing recommendation and results in administration of at least one adjusted dose of vancomycin.	From study enrollment to the longer of 7 days after the completion of vancomycin therapy or through 30 days from enrollment
Feasibility - Area under the curve sampling attainment after personalized dose adjustment	Percentage of patients who undergo dose adjustment and have subsequent area under the curve sampling performed	From study enrollment to the longer of 7 days after the completion of vancomycin therapy or through 30 days from enrollment
Efficacy and safety - area under the curve in goal range	Percentage of patients achieving area under the curve in goal range of 400-600mg-h/L.	From study enrollment to the longer of 7 days after the completion of vancomycin therapy or through 30 days from enrollment
Efficacy and safety - resolution of gram positive infection	Percentage of patients with resolution of gram positive infection within the standard antibiotic duration for the infectious etiology.	From study enrollment to the longer of 7 days after the completion of vancomycin therapy or through 30 days from enrollment
Efficacy and safety - development of acute kidney injury	Percentage of patients who develop acute kidney injury during the intervention.	From study enrollment to the longer of 7 days after the completion of vancomycin therapy or through 30 days from enrollment
Efficacy and safety - treatment failure	Percentage of patients with treatment failure.	From study enrollment to the longer of 7 days after the completion of vancomycin therapy or through 30 days from enrollment

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2026
• Primary Completion (Estimated): May 15, 2027
• Study Completion (Estimated): May 31, 2027

Study Registration Dates

• First Submitted: July 17, 2025
• First Submitted That Met QC Criteria: July 17, 2025
• First Posted (Actual): July 24, 2025

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: biomarker; pharmacokinetics; sepsis; vancomycin
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Sepsis; Anti-Bacterial Agents; Anti-Infective Agents; Vancomycin
• Other Study ID Numbers: 24-022663; K23DK119463 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all individual participant data (IPD) that underlie results in a publication
• IPD Sharing Time Frame: Starting 6 months after publication
• IPD Sharing Access Criteria: De-identified IPD and supporting information will be shared upon request and review by the primary investigator. A data use agreement will need to be in place prior to sharing data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No