Safety and Pharmacokinetics of Piperacillin-Tazobactam Extended Infusions in Infants and Children
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 141
- 试验地点
- 1
- 主要终点
- Evaluation of Clearance (CL) for piperacillin and tazobactam
研究概览
简要总结
Severe infection is one of the main causes of disease in hospitalized children and can be deadly. With the lack of novel antibiotics approved in children and the emergence of drug resistant bacteria, there is a critical need to optimize dosing of existing antibiotics. Piperacillin-tazobactam is an antibiotic frequently used for treatment of severe infection in children in Canadian hospitals. To optimize this antibiotic's efficacy despite the rise of antibiotic resistance, alternative dosing strategy is commonly used in adults, which consists of prolonging the time during which the drug is infused (4 hours instead of 30 min). Children clear piperacillin-tazobactam from their bodies at a slower rate than adults, consequently extended-infusion strategy cannot be directly extrapolated from adult to children. We believe that younger children need piperacillin-tazobactam infusions that are shorter compared to adults to achieve appropriate concentrations.
详细描述
This is a prospective, open-label Pharmacokinetics and safety study of piperacillin-tazobactam in children 2 months-6y of age.
Overall goal: To establish extended-infusion piperacillin-tazobactam dosing recommendations in infants and young children with normal renal function, for the treatment of sepsis due to resistant organisms. Dosing recommendations will be provided according to different levels of antibiotic resistance (MIC). We aim to establish the age threshold below which extended infusion does not provide additional therapeutic benefit because of immature renal function. We also aim to describe the PK of piperacillin-tazobactam standard dosing in children with acute kidney injury.
Study population #1: Normal Renal Function:
Evaluate the PK of piperacillin-tazobactam extended infusion in children 2 months-6y with normal renal function.
Hypothesis 1.1 : Population clearance of piperacillin will be 20% lower in infants 2-5 months compared with infants 6-23 months and will reach adult values at 2 years of age.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Months 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children 2 months - 6 years of age*
- •Piperacillin-tazobactam indicated per standard of care
- •Informed consent
排除标准
- •Insufficient venous access to allow extended infusion
- •History of anaphylaxis to β-lactams
- •Supported with extracorporeal membrane oxygenation (ECMO)
- •On renal replacement therapy
- •Cystic fibrosis
- •Acute Kidney injury
- •Chronic renal insufficiency defined as defined as a glomerular filtration rate of 10-60 mL/min/1.73 m2
- •Study population #2: Acute Kidney injury
- •Inclusion Criteria:
- •Children 2 months - 6 years of age
- •Piperacillin-tazobactam indicated per standard of care
- •Informed consent
- •Acute Kidney injury defined as the following:
- •Doubling of serum creatinine according to upper limit of normal for age and gender or
- •Doubling of baseline serum creatinine (defined as the creatinine level at admission, if the value is within normal limit for age and gender) We wil use the smaller value of these 2 definitions to diagnose acute kidney injury in a given subject.
- •Exclusion Criteria:
- •History of anaphylaxis to β-lactams
- •Supported with extracorporeal membrane oxygenation (ECMO)
- •On renal replacement therapy
- •Cystic fibrosis
- •Chronic renal insufficiency defined as defined as a glomerular filtration rate of 10-60 mL/min/1.73 m2
研究组 & 干预措施
Piperacillin-tazobactam
Piperacillin-tazobactam administration (fixed combination, ratio piperacillin:tazobactam = 8:1).
Recruitment stratified by age group and pediatric populations to ensure good representation of those subgroups. Maximum dose: 16g/day. Treatment duration: up to 14 days depending to the treating physician.
Patients with Normal Renal function:
- Pediatric and surgery units: 2-5 months (7); 6-11 months (7); 12-23 months (7); 2-6 years (16)
- Pediatric intensive care unit (PICU): 2-5 months (7); 6-11 months (7); 12-23 months (7); 2-6 years (16)
- Haematology-oncology unit: 2-5 months (7); 6-11 months (7); 12-23 months (7); 2-6 years (16)
Patients with Acute Kidney injury:
- Pediatric and surgery units: 2 months-6 years (10)
- PICU: 2 months-6 years (10)
- Haematology-oncology unit: 2 months-6 years (10)
干预措施: Piperacillin-tazobactam (Drug)
结局指标
主要结局
Evaluation of Clearance (CL) for piperacillin and tazobactam
时间窗: up to 14 days
Treatment days 1-14 followed by a safety observation period of 3 days after the last study dose.
Proportion of subjects who achieve Pharmacodynamic target (at least 50% of free plasma piperacillin concentration above the MIC [50% fT > MIC])
时间窗: up to 14 days
Treatment days 1-14 followed by a safety observation period of 3 days after the last study dose.
Evaluation of Volume of distribution (V) for piperacillin and tazobactam
时间窗: up to 14 days
Treatment days 1-14 followed by a safety observation period of 3 days after the last study dose.
次要结局
- Proportion of subjects experiencing adverse events (AEs)(up to 17 days)
研究者
Dr Julie Autmizguine
MD, MHS
St. Justine's Hospital