Vancomycin for Sepsis

(VAST-i Trial)

Overseen By Julie Fitzgerald, MD PhD

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's Hospital of Philadelphia

Must be taking: Vancomycin

Disqualifiers: CNS infection, Pregnancy, Dialysis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 30 days

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether personalized dosing models for vancomycin, an antibiotic, can improve treatment for children with sepsis. Sepsis is a severe infection, and the trial aims to determine if these new dosing methods can maintain optimal vancomycin levels—not too high or too low. By adjusting doses based on each child's kidney function, the trial seeks to treat infections effectively while minimizing side effects. Children admitted to an ICU with sepsis, who are on a ventilator or require medication for blood pressure, might be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking medical research.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that vancomycin is likely to be safe for children with sepsis?

Research has shown that vancomycin is generally safe when carefully monitored. About 90% of patients can be successfully treated with the right dose, typically between 40-60 mg per kilogram of body weight per day. Most people handle the drug well at these levels.

However, some risks exist. About 20% of patients might experience a negative reaction to the medicine, known as an adverse drug event (ADE). The risk of kidney problems increases if vancomycin levels in the blood become too high. Specifically, if the lowest concentration in the bloodstream, called the trough level, exceeds 15 mg/L, the risk of sudden kidney issues can triple.

The trial is in its early phase, focusing on understanding the safety of vancomycin for children with sepsis. At this stage, less safety information is available compared to later stages of research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new way to personalize vancomycin dosing for sepsis patients. Unlike standard treatments that use a one-size-fits-all approach, this method uses a personalized pharmacokinetic model that adjusts doses based on individual patient needs, specifically incorporating levels of urinary NGAL to guide adjustments. This approach aims to optimize effectiveness and minimize kidney damage, potentially leading to better outcomes for patients.

What evidence suggests that personalized vancomycin dosing could be effective for sepsis?

This trial will evaluate a personalized vancomycin pharmacokinetic model for dose adjustments in patients with sepsis. Studies have shown that personalized methods for vancomycin dosing enhance treatment accuracy. These methods predict the correct vancomycin levels in the blood, reducing the risk of kidney damage from excessive medication or ineffective treatment from insufficient dosing. A predictive method, such as one using machine learning, accurately estimates the vancomycin levels needed for effective treatment. Research indicates that personalized dosing can achieve target vancomycin levels that effectively combat infections while minimizing side effects. This approach promises improved sepsis management. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for children with sepsis, aiming to improve vancomycin dosing using personalized models based on individual kidney function. It seeks participants who can provide accurate information about their body's response to the drug.

Inclusion Criteria

I am older than 1 month and younger than 18 years.

My weight is between 5kg and 50kg.

I am prescribed vancomycin for at least 48 hours.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive personalized vancomycin dosing based on pharmacokinetic models and urinary NGAL levels, with adjustments made as needed

Up to 30 days

Daily monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment, including resolution of infection and kidney function

7 days after completion of vancomycin therapy

What Are the Treatments Tested in This Trial?

Interventions

• Vancomycin

Trial Overview The study tests whether personalized dosing adjustments of vancomycin in children with sepsis can achieve effective blood levels without causing kidney injury, by accounting for each child's unique metabolism.

How Is the Trial Designed?

Group I: Personalized vancomycin Pharmacokinetic model for dose adjustments Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12054080/

Machine learning and population pharmacokinetics This study developed four predictive models for sepsis patients receiving vancomycin treatment: the PPK model, Bayesian model, ML model, and ...

2. jpid.researchcommons.org jpid.researchcommons.org/cgi/viewcontent.cgi?article=1036&context=journal

Population Pharmacokinetics of Vancomycin and Dose ... Objectives: This study aimed to develop a population pharmacokinetic model for vancomycin in pediatric patients with sepsis or septic shock ...

3. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1549500/full

Machine learning approach for personalized vancomycin ... This study presents a robust random forest model that predicts vancomycin steady-state trough concentrations with high accuracy, offering a significant ...

4. journals.asm.org journals.asm.org/doi/10.1128/aac.00280-17

Pharmacokinetic Assessment of Vancomycin Loading Dose in ... The vancomycin loading dose (LD) of 25 to 30 mg/kg is a frequently practiced strategy to achieve effective concentrations from the first-treatment dose.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0883944119308135

Population pharmacokinetic model of Vancomycin based ... The present study aimed to establish a population pharmacokinetic model of vancomycin, including adult critically ill septic patients, with normal and impaired ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11669523/

Impact of vancomycin therapeutic drug monitoring on ... This finding suggests that empirical use of vancomycin with TDM can improve outcomes in sepsis patients, even when the etiological diagnosis is unclear.

7. bmcinfectdis.biomedcentral.com bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09927-4

Effect of low vs. high vancomycin trough level on the clinical ... This meta-analysis found no significant association between vancomycin trough levels and clinical outcomes in adult patients with sepsis or gram-positive ...

8. frontiersin.org frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1117717/full

Vancomycin efficiency and safety of a dosage of 40–60 mg ... Our study presented that about 90% patients could be treated successfully with the vancomycin dosage of 40-60 mg/kg/d and corresponding trough ...

9. accpjournals.onlinelibrary.wiley.com accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.2833

Patient safety outcomes for continuous infusion vancomycin ... Estimates vary, but approximately 20% of patients receiving vancomycin as OPAT experience an adverse drug event (ADE) during treatment.

10. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0924857923002376

Association between vancomycin therapeutic drug ... A vancomycin trough > 15 mg/L was associated with a three times higher risk of AKI (P = 0.003). An AUC24h of 420–650 mg*h/L was also associated with the lowest ...