Population Pharmacokinetic Model of Rifampicin in Staphylococcal Osteoarticular Infections
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 主要终点
- Area Under the Plasma Concentration-Time Curve (AUC) of Rifampicin
研究概览
简要总结
Staphylococcal osteoarticular infections (OAIs), including prosthetic joint infections and chronic osteomyelitis, represent a major cause of morbidity. Rifampicin is a key bactericidal antibiotic effective against staphylococcal biofilm. However, its pharmacokinetics exhibit substantial inter-individual variability due to complex hepatic metabolism and drug interactions. Currently, no prospective population pharmacokinetic (PopPK) model of rifampicin combined with levofloxacin or ciprofloxacin exists in patients with OAIs. Objectives:
The primary objective of this study is to develop a population pharmacokinetic model of oral rifampicin in patients undergoing medico-surgical treatment for staphylococcal osteoarticular infections. Secondary objectives include evaluating the pharmacokinetics of the partner antibiotic (levofloxacin or ciprofloxacin), investigating the correlation between antibiotic exposure metrics (AUC, Cmax, AUC/MIC) and clinical/biological tolerance, and assessing 1-year infection relapse-free survival and resistance emergence. Study Design:
Prospective, single-center, interventional study with minimal risks and constraints (RIPH 2) involving 40 participants recruited at the Reference Center for Complex Osteoarticular Infections (CRIOAC).
详细描述
Study Workflow and Pharmacokinetic Sampling Protocol:
Screening and Baseline: Adult patients hospitalized for staphylococcal prosthetic joint infection, chronic osteomyelitis, or native joint infection sensitive to rifampicin and levofloxacin/ciprofloxacin are screened. Clinical, demographic (age, sex, actual and ideal body weight), and biological data (renal function, liver function, serum albumin) are collected.
Pharmacokinetic Blood Sampling (12 samples total, 60 mL total volume): Day 2 / Day 3: 5 blood samples (5 mL each) collected pre-dose (t0, fasting) and at 1h, 2h, 4h, and 8h post-dose of rifampicin. Day 8 / Day 10: 5 blood samples (5 mL each) collected pre-dose (t0, fasting) and at 1h, 2h, 4h, and 8h post-dose of rifampicin and partner antibiotic (levofloxacin or ciprofloxacin). Day 28 / Day 32 (1-month follow-up visit): 2 blood samples (5 mL each) collected pre-dose and 2 hours post-dose during outpatient consultation.
Pharmacokinetic and Statistical Modeling: Population PK parameters (CL/F, V/F, ka) and inter-individual variability will be estimated using non-linear mixed-effects modeling (NONMEM v7.5). Influence of covariates (age, sex, weight, renal function, serum albumin) will be evaluated. One-Year Follow-up: Clinical follow-up at 12 months post-treatment initiation to evaluate infection relapse, tolerance, and microbiological
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient informed about the study and signed written consent obtained
- •Male or female participant aged 18 years or older
- •Staphylococcal osteoarticular infection (prosthetic joint infection of hip, knee, or shoulder; chronic osteomyelitis; or native joint infection) susceptible to rifampicin and levofloxacin or ciprofloxacin
- •Indication for combined medico-surgical treatment of the osteoarticular infection
排除标准
- •Septic shock requiring vasopressor support
- •Prior rifampicin treatment within 1 month preceding inclusion
- •Contraindication to rifampicin (known allergy, major drug interaction, or hepatic cirrhosis)
- •End-stage renal disease on chronic dialysis
- •Pregnant or breastfeeding woman
- •Adult patient unable or unfit to give informed consent
- •Subject deprived of liberty by judicial or administrative decision
- •Subject not affiliated with or beneficiary of a national social security scheme
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve (AUC) of Rifampicin
时间窗: Day 2/3, Day 8/10, and Day 28/32 post-initiation of antibiotic therapy
Area under the plasma concentration-time curve of oral rifampicin, estimated using a population pharmacokinetic non-linear mixed-effects model (NONMEM).
Peak Plasma Concentration (Cmax) of Rifampicin
时间窗: Day 2/3, Day 8/10, and Day 28/32 post-initiation of antibiotic therapy
Maximum observed plasma concentration (Cmax) of oral rifampicin, measured following administration.
Apparent Oral Clearance (CL/F) of Rifampicin
时间窗: Through 4 weeks post-initiation of antibiotic therapy
Apparent oral clearance (CL/F) of rifampicin estimated using a population pharmacokinetic model (NONMEM), including evaluation of inter-individual variability and covariate effects.
Apparent Volume of Distribution (V/F) of Rifampicin
时间窗: Through 4 weeks post-initiation of antibiotic therapy
Apparent volume of distribution (V/F) of rifampicin estimated using a population pharmacokinetic model (NONMEM), including evaluation of inter-individual variability and covariate effects.
次要结局
- Incidence of Clinical and Biological Adverse Events Related to Rifampicin Exposure(Through 4 weeks post-initiation of antibiotic therapy)
- Infection Relapse-Free Survival at 1 Year Relative to Rifampicin AUC/MIC Ratio(12 months post-initiation of antibiotic therapy)
- Emergence of Rifampicin Resistance at Relapse(12 months post-initiation of antibiotic therapy)
- Peak Plasma Concentration (Cmax) of Partner Antibiotic(Day 8/10 and Day 28/32 post-initiation of antibiotic therapy)
- Trough Plasma Concentration (Cmin) of Partner Antibiotic(Day 8/10 and Day 28/32 post-initiation of antibiotic therapy)
- Apparent Clearance (CL/F) of Partner Antibiotic(Day 8/10 and Day 28/32 post-initiation of antibiotic therapy)
- Area Under the Plasma Concentration-Time Curve (AUC) of Partner Antibiotic(Day 8/10 and Day 28/32 post-initiation of antibiotic therapy)