Prospective Pilot Study to Evaluate a Standardized Management of Cryptococcal Meningitis in Patients Infected With HIV in Sub-Saharan Africa Involving an Initial Combination Therapy With Fluconazole and Flucytosine in High Doses, Complemented by Repeat Lumbar Punctures
试验速览
- 阶段
- 2 期
- 入组人数
- 41
- 试验地点
- 5
- 主要终点
- Mortality rate
研究概览
简要总结
The aim of the trial is to demonstrate that in a sub-Saharan African setting, the association of:
- Oral treatment : high dose of fluconazole (1600mg/d) associated with flucytosine (100 mg/kg/j) as induction therapy
- lumbar punctures to control intracranial pressure
can decrease mortality rate below 35% at 10 weeks.
This is a non-randomized open label pilot study, with standardized management of cryptococcoses meningitis and follow-up in Burundi and Ivory Coast. A total of 41 patients will be enrolled.
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
- •> 18 years
- •HIV Infection
- •First episode of cryptococcal meningitis on basis CSF India ink and/or CSF cryptococcal antigen.
- •Glasgow > 9 after lumbar punctures
- •Absence of peripheral focal deficit in the limbs
- •informed consent signed
排除标准
- •Hemoglobin <7.5 g / dl;
- •neutrophils count <500/mm3;
- •Platelets count <50 000/mm3;
- •transaminases > 5 times upper limit of normal;
- •Troubles with severe mental alertness Glasgow <9 after the initial lumbar puncture;
- •focal neurological deficit in the limbs;
- •Pregnancy or lactation on going;
- •Ongoing systemic antifungal treatment;
- •History of cryptococcal meningitis;
- •Ongoing rifampicin and ritonavir treatment;
- •Subject participating in another study with a risk of mutual interference on the interpretation of results.
研究组 & 干预措施
oral treatment
Drug: Fluconazole and flucytosine
Induction treatment for 2 weeks:
Fluconazole (1600mg/j) + flucytosine (100 mg/kg/j) lumbar punctures to control intracranial pressure Consolidation treatment for 8 weeks: fluconazole (800 mg/j)
干预措施: Fluconazole (Drug)
oral treatment
Drug: Fluconazole and flucytosine
Induction treatment for 2 weeks:
Fluconazole (1600mg/j) + flucytosine (100 mg/kg/j) lumbar punctures to control intracranial pressure Consolidation treatment for 8 weeks: fluconazole (800 mg/j)
干预措施: Flucytosine (Drug)
oral treatment
Drug: Fluconazole and flucytosine
Induction treatment for 2 weeks:
Fluconazole (1600mg/j) + flucytosine (100 mg/kg/j) lumbar punctures to control intracranial pressure Consolidation treatment for 8 weeks: fluconazole (800 mg/j)
干预措施: lumbar punctures (Procedure)
结局指标
主要结局
Mortality rate
时间窗: 10 weeks
次要结局
- Mortality rate(14 days and 24 weeks)
- Concentration of flucytosine in plasma(28 days or 10 weeks)
- MICs of fluconazole(28 days)
- Number of "Immune Reconstitution Inflammatory Syndrome" (IRIS) throughout the monitoring period(up to 24 weeks)
- Number and severity of adverse events(up to 24 weeks)
- Cerebrospinal fluid pressure evolution(up to 24 weeks)
- CD4 count(24 weeks)
- Concentration of flucytosine in cerebrospinal fluid(28 days or 10 weeks)
- Sensitivity of cryptococcal antigen by strip method LFA (lateral-flow immunoassay)(at study entry)
- CSF total volume discharged(up to 24 weeks)
- Percentage of patients with negative cerebrospinal fluid (CSF) cultures(14 days and 10 weeks)
- Number of lumbar punctures performed(up to 24 weeks)
- Concentration of fluconazole in cerebrospinal fluid(28 days or 10 weeks)
- Number of relapses of cryptococcal throughout the monitoring period(up to 24 weeks)
- Concentration of fluconazole in plasma(28 days or 10 weeks)
- Percentage of patients with undetectable viral load(24 weeks)