Trial for the Optimal Timing of HIV Therapy After Cryptococcal Meningitis
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 177
- 试验地点
- 3
- 主要终点
- Mortality
研究概览
简要总结
The Cryptococcal Optimal ART Timing (COAT) trial seeks to determine after cryptococcal meningitis (CM) whether early initiation of antiretroviral therapy (ART) prior to hospital discharge results in superior survival compared to standard initiation of ART started as an outpatient.
详细描述
After 7-11 days of amphotericin B therapy, subjects will be randomized in a 1:1 allocation to:
- Early initiation of ART (Experimental Group) = ART initiated within 48 hours after study entry, OR
- Standard initiation of ART (Control Group) = ART at >=4 weeks after study entry
HIV therapy will be with efavirenz plus nucleoside backbone per national guidelines for first line therapy.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 14 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-infection, documented by ELISA
- •Antiretroviral medication naïve (excluding mother-to-child transmission therapy)
- •Age >14 years
- •Cryptococcal meningitis diagnosed by either culture or CSF cryptococcal antigen (CRAG)
- •Ability and willingness of the participant or legal guardian/representative to give informed consent.
- •Receiving amphotericin-based anti-fungal therapy
排除标准
- •Study entry prior to receipt of <7 days or >11 days of amphotericin therapy
- •History of prior, known cryptococcal meningitis
- •Inability to take enteral medication
- •Receiving chemotherapy or other immunosuppressant medications
- •Cannot or unlikely to attend regular clinic visits
- •Contraindication to immediate or delayed HIV therapy based on serious co-morbidities or co-infections, or laboratory values
- •Pregnancy or Breastfeeding
- •Female participants of childbearing potential who are participating in sexual activity that could lead to pregnancy must agree to use two reliable methods of contraception
研究组 & 干预措施
Earlier HIV Therapy
HIV therapy initiated at 7-13 days of cryptococcal meningitis diagnosis. HIV therapy consisting of a nucleoside with lamivudine and efavirenz.
干预措施: efavirenz (Drug)
Earlier HIV Therapy
HIV therapy initiated at 7-13 days of cryptococcal meningitis diagnosis. HIV therapy consisting of a nucleoside with lamivudine and efavirenz.
干预措施: nucleoside (Biological)
Deferred HIV Therapy
HIV therapy initiated at 5 weeks after cryptococcal meningitis diagnosis (+/- 1 week).
HIV therapy consisting of a nucleoside with lamivudine and efavirenz.
干预措施: efavirenz (Drug)
Deferred HIV Therapy
HIV therapy initiated at 5 weeks after cryptococcal meningitis diagnosis (+/- 1 week).
HIV therapy consisting of a nucleoside with lamivudine and efavirenz.
干预措施: nucleoside (Biological)
结局指标
主要结局
Mortality
时间窗: 26 weeks from study entry
Intention to treat analysis of 26 week survival of all subjects enrolled. Reported below are the numbers of participants who died by Week 26.
次要结局
- Safety of ART Initiation(46 weeks)
- Karnofsky Functional Status(46 weeks)
- Incidence of Immune Reconstitution Inflammatory Syndrome(46 weeks)
- HIV-1 Viral Suppression(26 weeks)
- Antiretroviral Therapy Tolerability(26 weeks)
- 46-week Survival(46 weeks)
- Incidence of Cryptococcal-relapse(46 weeks)
- Microbiologic Clearance(4 weeks)