Early Discontinuation of Antibiotic Therapy in High-Risk Febrile Neutropenic Pediatric Oncology Patients

The primary objective is to evaluate the safety of discontinuing antibiotic therapy in pediatric patients with cancer experiencing febrile neutropenia without a proven invasive bacterial infection. Clinical relevance is determined by comparing the proportion of episodes reaching uncomplicated resolution 28 days after onset. Uncomplicated resolution is defined by the absence of death, intensive care unit admission, sepsis, or microbiologically and clinically documented bacterial infections. Eligibility for early discontinuation is based on clinical stability, fever resolution, an absolute neutrophil count below 500/mm³, and specific low levels of C-reactive protein or procalcitonin at 48–72 hours after the onset of the febrile episode.

Secondary objectives include:

• Evaluating the efficacy of the discontinuation strategy by assessing the reduction in the total number of antibiotic days.
• Assessing the reduction in adverse events related to prolonged antibiotic therapy.
• Retrospectively evaluating the utility of biomarkers, including interleukin-8, for the prediction of invasive bacterial infection.
• Validating a prediction system for invasive bacterial infection within this specific patient population.

The sponsor did not provide the total number of participants. The study population consists of male and female pediatric patients, aged 2 to 12 years, diagnosed with various forms of cancer, including acute lymphoblastic leukaemia, acute myeloblastic leukaemia, biphenotypic leukaemia, lymphoblastic lymphoma, anaplastic lymphoma, B-cell lymphoma, solid tumours, or relapsed leukaemia. Eligible participants must experience an episode of febrile neutropenia characterized by an absolute neutrophil count below 500/mm³. Included individuals must demonstrate clinical stability and a low risk of invasive bacterial infection, defined by specific biochemical markers including C-reactive protein and procalcitonin levels. The study focuses on patients who show good clinical evolution and an absence of proven or suspected infectious diseases 48–72 hours after the onset of the febrile episode.

This Phase IV, randomized, open-label, parallel groups clinical trial aims to evaluate the safety of early discontinuation of antibiotic therapy in pediatric patients with cancer experiencing febrile neutropenia without a proven invasive bacterial infection. The study is designed to compare the proportion of episodes with uncomplicated resolution at 28 days between an experimental group and a control group. The trial is estimated to recruit participants between March 2026 and March 2028. The study procedures begin with a screening process to ensure patients meet specific criteria, including an absolute neutrophil count below 500/mm³, stable clinical evolution, and specific low biomarker levels, such as C-reactive protein and procalcitonin, at 48–72 hours after the onset of the episode. Following randomization, participants receive assigned treatments, which may include various antimicrobials administered via intravenous infusion or oral routes. Follow-up assessments include laboratory monitoring and clinical evaluations at 5 days and 28 days to monitor for complications such as sepsis or intensive care unit admission. The total duration of involvement is determined by the clinical course and the 28-day follow-up period. Early termination may occur if clinical or radiological findings suggest a localized or invasive infection.

The clinical trial involves the administration of several investigational antibiotic treatments for pediatric patients experiencing febrile neutropenia. The experimental medications include cefepime administered via intravenous infusion at a dose of 150 mg/kg.

Teicoplanin is administered through intravenous infusion at a dosage of 12 mg/kg. Metronidazole is utilized in two different formats: via oral administration at 30 mg/kg or through intravenous infusion at 30 mg/kg.

Meropenem is administered via intravenous infusion at a dose of 120 mg/kg. Tazobactam is provided through intravenous infusion at a dosage of 37.5 mg/kg. Vancomycin is administered via intravenous infusion at a dose of 60 mg/kg.

Levofloxacin is administered in two forms: oral at 20 mg/kg and via intravenous infusion at 20 mg/kg. Ciprofloxacin is also provided in two routes: oral at 40 mg/kg and via intravenous infusion at 30 mg/kg.

Ceftazidime is administered via intravenous infusion at a dose of 150 mg/kg. Amikacin is administered through intravenous infusion at a dosage of 22.5 mg/kg. Piperacillin is provided via intravenous infusion at a dose of 400 mg/kg.

The efficacy of discontinuing antibiotic therapy is primarily assessed by comparing the proportion of febrile neutropenia episodes achieving uncomplicated resolution at 28 days from the onset of the episode between the experimental and control groups. Uncomplicated resolution is defined by the absence of death from any cause, intensive care unit admission, sepsis, microbiologically documented bacterial infection, or clinically documented bacterial infection, including radiologically confirmed pneumonia.

Secondary efficacy and safety parameters include:

• Duration of fever and neutropenia.
• Duration and type of antimicrobials administered.
• Laboratory values, including complete blood count, serum biochemistry, C-reactive protein, and procalcitonin, measured at the onset of the episode, at 48–72 hours, at 5 days if applicable, and at 28 days.
• Levels of interleukin-8 measured at the onset of neutropenic fever and at 48–72 hours.
• Microbiological results from blood cultures, urine cultures, and other specimens such as nasopharyngeal swabs or cerebrospinal fluid.
• Results of beta-human chorionic gonadotropin in urine.
• Imaging test results, such as X-ray, computed tomography, magnetic resonance imaging, or ultrasound.
• Incidence and severity of adverse events.
• Concomitant medication.