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
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Achievement of antibiotic concentration targets in the intervention group (1i) vs control groupe (1c)
研究概览
简要总结
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.
详细描述
Background and Rationale In pediatric cancer patients, Augmented Renal Clearance (ARC) is a common factor that affects outcomes. Febrile neutropenia, a frequent occurrence during cancer treatment, requires anti-infective drugs for treatment. However, ARC increases the elimination of these drugs through glomerular filtration, posing a risk of antibiotics insufficient blood levels. This may lead to difficulties in managing infections and the risk of antibiotic-resistant bacterial strains emerging. Febrile neutropenia is often associated with ARC, and in these patients standard antibiotic dosages frequently miss target concentrations. We propose defining categories of renal hyperfiltration to adjust antibiotic dosages upward in pediatric patients with ARC.
To estimate renal function, molecules such as creatinine or cystatin C are routinely measured in the blood. Clinicians commonly rely on the Schwartz formula for determining the patients glomerular filtration rate (GFR) when adjusting antibiotic treatment. Although other formulas based on creatinine and/or cystatin C have been developed, their effectiveness in oncological patients with ARC remains unexplored. If these alternative formulas prove more effective in ARC situations, it may prompt a reconsideration of how we determine GFR in hyperfiltrating children.
Measurement and procedures Clinicians will decide if prescribe piperacillin-tazobactam or meropenem, according to the clinical situation. The trial will have 3 arms, the two control arms will receive standard dosages of antibiotics (non-hyperfiltrating patients, control group 2, and hyperfiltrating patients randomized to control group 1c). The third group, hyperfiltrating patients randomized to intervention group 1i, will receive experimental doses. The randomization will be made using REDCap®.
A TDM at trough level (Ctrough) of meropenem (MER) or piperacillin-tazobactam (PIP) will be systematically performed just before the fourth dose, and again before the fourth dose after each further dosage adaptation. The dosage will be adjusted if blood levels are outside the target therapeutic ranges. TDM will be monitored at least twice a week and more frequently in case of unfavorable clinical outcome or significant change in serum creatinine.
Objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 61 Days 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Control Group 2
Control Group 2 includes patients with normal or decreased renal function who will receive standard dosage of antibiotic (méropenem or piperacilline-tazobactam)
干预措施: Standard dosages of piperacillin-tazobactam or meropenem (Drug)
Control Group 1c
Group 1c includes patients with augmented renal clearance (ARC) who have been randomized to receive a standard dosage of antibiotic (méropenem or piperacilline-tazobactam)
干预措施: Standard dosages of piperacillin-tazobactam or meropenem (Drug)
Intervention DAR-ARC Group 1i
Group 1i (DAR-ARC) includes patients with ARC who have been randomized to receive an experimental dosage of antibiotic (méropenem or piperacilline-tazobactam)
干预措施: Dosage Adjustment Rules for Augmented Renal Clearance (DAR-ARC) for piperacillin-tazobactam and meropenem (Drug)
结局指标
主要结局
Achievement of antibiotic concentration targets in the intervention group (1i) vs control groupe (1c)
时间窗: During the first 24 hours of the intervention, before the fourth dose of antibiotic
Intervention-drug blood concentration both above the lower limit and below the upper limit of the therapeutic target ranges on the first trough dosage before the fourth dose after treatment initiation.
次要结局
- Achievement of antibiotic concentration targets in control group 2(During the first 24 hours of the intervention, before the fourth dose of antibiotic)
- Number of dosage adjustments required to achieve the target concentration(During the intervention)
- Difference between eGFR measured by creatinine-based Schwartz formula and other eGFR calculation formulas(Baseline, pre-intervention)
- Fever duration(During the intervention)
- Side effects of antibiotic therapy(During the intervention and up to 2 weeks after)
研究者
Pierre Alex Crisinel
Head of the Unit of Pediatric Infectious Diseases and Vaccinology
Centre Hospitalier Universitaire Vaudois