Upwards Initial Adjustment of Wide-Spectrum Antibiotic Dosage in Pediatric Oncology Patients With Febrile Neutropenia and Suspected Augmented Renal Clearance: A Randomized Controlled Trial With Therapeutic Drug Monitoring

2023-01013

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.

2024-03-01

2026-03-01

2026-03-01

Not yet recruiting

Early phase I

30

Patients' inclusion criteria * Oncologic patients aged 2 months to 17 years (older than 60 days and younger than 18 years), * High probability of febrile neutropenia during the study period * Written informed consent from parents and adolescents older than 14 years Patients' exclusion criteria * Neutropenia not related to cancer and/or chemotherapy * Refusal to participate * Non-French speaking parents/patients older than 11 years old * Absence of febrile neutropenia or agranulocytosis during the study period (secondary exclusion) Febrile neutropenia episodes inclusion criteria * Febrile neutropenia or agranulocytosis defined as: * Neutropenia: absolute neutrophils \<500 cells/µL or agranulocytosis: absolute neutrophils \<100 cells/µL or patients expected to be neutropenic in the next 24 hours due to ongoing chemotherapy * body temperature (tympanic or axillary) ≥38°C during at least one hour or a single T ≥38.5°C * At least 2 weeks after the end of the previous antibiotic treatment for another included episode of febrile neutropenia. Febrile neutropenia episodes exclusion criteria: * Severe renal failure (GFR\<15 mL/min/1.73 m²) * Pregnancy * Inability to obtain the first therapeutic drug monitoring (TDM) result within 72 hours of sampling (e.g. admission before or during public holidays laboratory closure)

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Our study is an open-label, re-randomized controlled trial in multi-episodes settings. So the care team, researchers and patients will be informed of the allocation group. Patients will be able to participate in each episode of febrile neutropenia. At each inclusion the patient may be in a different group.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 30, 'type': 'ESTIMATED'}}

2024-03-05