Vancomycin and Acute Kidney Injury in Sepsis Treatment - Intervention

Official title

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

Overview

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?

Interventions

• 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.

Primary outcome measures

• Feasibility - personalized dose adjustment performed [Time frame: From enrollment to the longer of 7 days after the completion of vancomycin therapy or through 30 days from enrollment]

Secondary outcome measures (8)

• Feasibility - Use of study-determined empiric vancomycin dosing [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: From study enrollment to the longer of 7 days after the completion of vancomycin therapy or through 30 days from enrollment]

Eligibility criteria

Inclusion criteria

• Age >1 month and <18 years
• Weight >5kg and <50kg
• Vancomycin intended duration of therapy ≥48 hours
• Admitted to intensive care unit with suspected or confirmed sepsis
• 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

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Children's Hospital of Philadelphia — Philadelphia

Identifiers

NCT: NCT07084129 · 24-022663 · K23DK119463

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗