Randomised Controlled Trial of Immediate Versus Deferred Antiretroviral Therapy for HIV-Associated Tuberculous Meningitis
试验速览
- 阶段
- 不适用
- 入组人数
- 253
- 试验地点
- 2
- 主要终点
- Mortality
研究概览
简要总结
The optimal time to initiate antiretroviral therapy (ART) in HIV-associated tuberculous meningitis (TBM) unknown. There are concerns that immediate ART may worsen rather than improve outcome, because drug interactiond and toxicities or development of an intracerebral immune reconstitution inflammatory syndrome (IRIS). Conversely, delaying ART may result in increased HIV-related deaths. To answer this question, we are conducting a randomised, double-blind placebo-controlled trial comparing immediate and deferred ART in HIV-infected patients presenting with TBM, to assess effect on survival.
详细描述
Title: Study of immediate versus deferred antiretroviral therapy in HIV-associated tuberculous meningitis Study design: A randomized, double blind, placebo-controlled trial with 2 parallel arms Sample size: 247 Inclusion criteria: Age 15 years or older; HIV antibody positive; clinical diagnosis of TBM.
Exclusion criteria: positive CSF Gram or India ink stain, known or suspected pregnancy; antituberculous treatment 8 to 30 days immediately prior to recruitment; previous antiretroviral therapy; laboratory contraindications to antiretroviral or antituberculous therapy; lack of consent.
Consent: Written informed consent will be sought for all patients. Verbal consent will be considered acceptable when written consent is impossible. In unconscious patients, the consent of 2 independent physicians will be considered acceptable.
Randomization: Patients will be stratified according to TBM disease severity at presentation (modified MRC grade I to III). Within each stratum, patients will be randomized to 1 of the 2 treatment arms: immediate or deferred (2 months) ART.
Antituberculous treatment: Initial therapy will be with isonazid, rifampicin, pyrazinamide and ethambutol for 3 months. After 3 months, patients will continue on rifampicin and isoniazid for a further 6 months.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age 15 years or older
- •HIV antibody positive
- •clinical diagnosis of TB meningitis
排除标准
- •positive CSF Gram or India ink stain
- •known or suspected pregnancy
- •antituberculous treatment 8 - 30 days immediately prior to recruitment
- •previous antiretroviral therapy
- •laboratory contraindications to antiretroviral or antituberculous therapy
- •lack of consent.
研究组 & 干预措施
1
Combivir, efavirenz for 12 months
干预措施: Combivir and efavirenz (Drug)
2
Placebo for 2 months followed by Combivir and efavirenz for 10 months
干预措施: Combivir and efavirenz (Drug)
结局指标
主要结局
Mortality
时间窗: 9 months
次要结局
- Mortality(12 months)
- Fever clearance time
- Coma clearance time
- CD4 count(12 months)
- plasma HIV RNA(12 months)
- Grade 3 or 4 adverse event(Any)
- Neurological disability(12 months)