Explorative PK Study Comparing 600 mg Rifampicin i.v. With 750 mg and 900 mg Rifampicin Oral in Tuberculous Meningitis Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Pharmacokinetic profile of several rifampicin dose
研究概览
简要总结
Tuberculous (TB) meningitis is the most severe manifestation of TB infection, leaving up to 50% of patients dead or neurologically disabled. Current treatment is similar to treatment of lung TB, although penetration of some antibiotics into the brain is poor and the immune-pathology of TB meningitis is very different from pulmonary TB. In a recent phase II clinical trial from the investigators group, the first of its kind globally, intensified antibiotic treatment, with moxifloxacin and high dose rifampicin, strongly reduced mortality of TB meningitis.
The investigators aim to examine the effect of intensified antibiotic treatment on mortality and morbidity of TB meningitis in a phase 3 clinical trial, preceded with an explorative pharmacokinetic (PK) study to examine if higher oral doses rifampicin result in exposures similar to the i.v. dose used in our phase 2 trial, since oral rifampicin could be implemented much easier in low-resource settings.
详细描述
Introduction:
In a recent clinical trial the investigators have shown that a higher dose of rifampicin administered intravenously (600 mg iv) during the first 2 weeks of treatment is safe and associated with a survival benefit in adults with TB meningitis. An oral (rather than iv) dose would help implementation of intensified treatment for TB meningitis. However, it is hard to predict what oral dose of rifampicin will result in rifampicin exposures similar to 600 mg iv, due to differences in bio-availability (oral vs. iv) and the unpredictable dose-concentration relationship (nonlinear pharmacokinetics of rifampicin). Therefore the investigators aim to examine the pharmacokinetic of 2 higher doses of rifampicin (750 mg and 900 mg) given orally, and compare the pharmacokinetic profiles with the result of our previous study using 600 mg rifampicin iv.
General Objective:
To help establish the optimized treatment regimen for TB meningitis
Specific 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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older
- •Probable/possible tuberculosis meningitis using uniform case definition
- •Agree to participate in the study
排除标准
- •Patient with antituberculosis treatment within last 2 weeks.
- •Increase liver function >5x upper limit of normal
- •Pregnancy
研究组 & 干预措施
Rifampicin 600 mg
Subjects in this arm receive 600 mg rifampicin intravenously
干预措施: Rifampicin intravenous (Drug)
rifampicin 750 mg
Subjects in this arm receive 750 mg rifampicin orally
干预措施: Oral rifampicin (Drug)
rifampicin 900 mg
Subjects in this arm receive rifampicin 900 mg orally
干预措施: Oral rifampicin (Drug)
结局指标
主要结局
Pharmacokinetic profile of several rifampicin dose
时间窗: Day 2 and Day 14; 6 time points for blood analysis, and 1 time point for CSF analysis
We will measure plasma drug concentration at hour 0, 1, 2, 4, 8, and 12, while CSF drug concentration will be measured at a single time point i.e. at hour 3-6 post dose. The sampling days will be (1) within the first three days, and (2) at day 14 of the intensified treatment.
次要结局
- mortality(early (1 month) and late (6 months))