Pharmacokinetics and Safety of Meropenem in Infants Below 90 Days of Age (Inclusive) With Probable and Confirmed Meningitis: A European Multicenter Phase I-II Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Pharmacokinetics of Meropenem (plasma and CSF) in infants ≤ 90 days of age diagnosed with probable and confirmed bacterial meningitis.
研究概览
简要总结
This phase I-II multicenter international trial is designed to study the pharmacokinetics of meropenem and to characterize the safety profile of meropenem in the treatment of infants ≤ 90 days of postnatal age with probable or confirmed bacterial meningitis.
详细描述
The primary objective will be to study the pharmacokinetics (plasma and cerebrospinal fluid) of meropenem in infants ≤ 90 days of postnatal age with probable or confirmed bacterial meningitis and to characterize the safety profile of meropenem in the treatment of infants ≤ 90 days of postnatal age with probable or confirmed bacterial meningitis.
The secondary objectives are :
- To describe the efficacy of meropenem on day 3, at end of allocated treatment (EOAT), at test of cure (TOC) and at follow up (FU).
- To evaluate survival at FU
- To evaluate further episodes of meningitis (relapse or new infection) occurring between TOC and FU visits
- To define the organisms causing neonatal meningitis
- To describe the antibacterial susceptibility of meningitis-causing organisms and to describe the clinical and microbiological response according to this
- To evaluate mucosal colonization by resistant organisms before and after treatment with meropenem
- To evaluate bacterial eradication
- To evaluate functional genetic parameters that may affect response to therapy
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
- — 至 90 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent form signed by the parents/carers
- •Chronological age below 90 days inclusive
- •The presence of:
- •clinical signs consistent with BM (hyperthermia or hypothermia or temperature instability PLUS 1 or more neurological findings among coma, seizures, neck stiffness, apnoea, bulging fontanelle),
- •OR CSF pleocytosis (≥ 20 cells/mm3)
- •OR a positive Gram stain of CSF.
排除标准
- •Presence of a CSF device
- •Proven viral or fungal meningitis
- •Severe congenital malformations if the infant is not to expect to survive for more than 3 months
- •Other situations where the treating physician considers a different empiric antibiotic regimen necessary
- •Known intolerance or contraindication to the study medication
- •Participation in any other clinical study of an investigational medicinal product
- •Renal failure and requirement of haemofiltration or peritoneal dialysis
- •Meningitis with an organism known to be resistant to meropenem
研究组 & 干预措施
Meropenem
Infants will received Meropenem 40 mg/kg every 8 hours (every 12 hours in the youngest age group: < 32 weeks GA and < 2 weeks postnatal age).
Treatment duration = 21 ± 7 days
干预措施: Meropenem (Drug)
结局指标
主要结局
Pharmacokinetics of Meropenem (plasma and CSF) in infants ≤ 90 days of age diagnosed with probable and confirmed bacterial meningitis.
时间窗: 3-4 days
Pharmacokinetic analyses (AUC) will be carried out on the infants who received at least one dose of meropenem after inclusion in NeoMero-2. The final model will be used for dosing simulations to give final dose recommendations.
Nature, frequency and numbers of all adverse events under meropenem.
时间窗: Up to 48 days
Adverse events will also be summarised according to the need of a specific medical intervention or not. Analyses by time period will also be shown (from D0 to TOC visit and from TOC visit to follow-up).
次要结局
- Percentage of patients with a favourable outcome defined at Test of Cure visit (TOC).(An expected average of 21 days)