Adjustment of Antibiotic Dosage in Pediatric Oncology Patients With Febrile Neutropenia and Augmented Renal Clearance

Summary

This clinical trial focuses on children with cancer who face infections after receiving chemotherapy. Chemotherapy affects the bone marrow, leading to a decrease in the production of certain white blood cells, particularly those that defend against bacterial infections (neutrophils). One significant concern is febrile neutropenia, where children experience a fever during a period of low white blood cell count. This condition often results from bacterial infections, necessitating prompt wide-spectrum antibiotic treatment. However, some children eliminate antibiotics in the urine too quickly during febrile neutropenia. Their kidneys function more than they normally do (renal hyperfiltration). This can lead to insufficient exposure to antibiotics to control the infection. The current standard antibiotic regimens do not account for this variable elimination rate. In this study we focus on two antibiotics used in this context: piperacillin-tazobactam and meropenem.

The main questions this study aims to answer are, in these children:

* Would higher doses of antibiotics result in better blood levels of antibiotics?
* Would they have more sides effects with higher antibiotics dosages?
* Would they recover more quickly with higher antibiotic doses? All patients will undergo a blood test upon hospital arrival, including an assessment of renal function. If renal function is normal or diminished, the patient will receive the standard antibiotic dose. Children with increased renal function will be randomly assigned to two groups during each episode of febrile neutropenia. One group will receive standard antibiotic dosages, while the other will receive higher doses to compensate for renal hyperfiltration. Throughout the study, antibiotic levels in the blood will be monitored for all patients. This monitoring will determine if target concentrations can be achieved more quickly with experimental dosages and will allow doctors to readjust the doses if needed.

Conditions

• Febrile Neutropenia

Interventions

DRUG

Dosage Adjustment Rules for Augmented Renal Clearance (DAR-ARC) for piperacillin-tazobactam and meropenem

Meropenem dosages according to eGFR \[mL/min/1.73 m²\] : eGFR 120-149 : 40 mg/kg q6 h eGFR 150-199 : 30 mg/kg q4h eGFR 200-299 : 40 mg/kg q4h eGFR \>/= 300 : 40 mg/kg q4h Piperacillin-tazobatam dosages according to eGFR \[mL/min/1.73 m²\] : eGFR 120-149 : 150 mg/kg q6 h eGFR 150-199 : 120 mg/kg q4h eGFR 200-299 : 150 mg/kg q4h eGFR \>/= 300 : 180 mg/kg q4h The maximum doses for the antibiotic prescription before the first drug monitoring will be 2gr of MER every 4 hours and 4gr of PIP every 4 hours. The duration of infusion will be set to 2 h.

DRUG

Standard dosages of piperacillin-tazobactam or meropenem

Meropenem dosages according to eGFR \[mL/min/1.73 m²\] : eGFR\> 50 : 40mg/kg q8h eGFR 25-49 : 40mg/kg q12h eGFR 15-24 : 20mg/kg q12h Piperacillin-tazobactam : eGFR \>50 : 100mg/kg q6h eGFR 20-49 : 50mg/kg q6h eGFR 15-29 : 50 mg/kg q8h

Sponsors & Collaborators

• Unisanté Centre universitaire de médecine générale et santé publique

  collaborator UNKNOWN

• FORCE Fondation Recherche sur le Cancer de l'Enfant

  collaborator UNKNOWN

• Centre Hospitalier Universitaire Vaudois

  lead OTHER

Principal Investigators

• Pierre-Alex Crisinel · Centre Hospitalier Universitaire Vaudois

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

61 Days

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-03-01

Primary Completion

2026-03-31

Completion

2026-03-31

Countries

• Switzerland

Study Locations