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

Children's Hospital of Philadelphia (CHOP)

Status and phase: Enrolling; Phase 1

Conditions: Sepsis

Treatments: Other: personalized dosing adjustment of vancomycin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07084129

K23DK119463 (U.S. NIH Grant/Contract)

24-022663

Details and patient eligibility

About

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?

Enrollment: 20 estimated patients

Sex: All

Ages: 1 month to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Personalized vancomycin Pharmacokinetic model for dose adjustments

Experimental group

Description:

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.

Treatment:

Other: personalized dosing adjustment of vancomycin