Adjunctive Sertraline for the Treatment of HIV-Associated Cryptococcal Meningitis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 460
- 试验地点
- 2
- 主要终点
- Survival
研究概览
简要总结
This is a phase III trial to determine whether adjunctive sertraline will lead to improved survival 18-week survival.
There was an initial phase I/II unmasked dose finding pharmacokinetic study of CSF concentrations in 172 persons conducted from August 2013 to August 2014. See NCT03002012.
详细描述
This is a phase III randomized trial to evaluate whether sertraline when added to standard amphotericin-based therapy for cryptococcal meningitis, will lead to improved survival . Cryptococcal meningitis diagnosis will be made via CSF cryptococcal antigen (CRAG) at time of lumbar puncture (LP) with confirmation by CSF culture. After informed consent, subjects that meet eligibility requirements will be able to enter study. A non-randomized phase I dose-escalation study will first be conducted to help optimize dosing for a larger randomized phase II study.
Phase III Design: Subjects will be randomized to standard induction therapy with masked placebo or sertraline at 400mg/day. We will use a permutated block randomization in a 1:1 allocation (n=275 per arm). Total anticipated enrollment: 550 subjects.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Cryptococcal meningitis diagnosed by CSF cryptococcal antigen (CRAG)
- •HIV-1 infection
- •Ability and willingness of the participant or legal guardian/representative to provide informed consent
- •Willing to receive protocol-specified lumbar punctures
排除标准
- •Age < 18 years
- •Receipt of >=3 doses of amphotericin therapy
- •Cannot or unlikely to attend regular clinic visits
- •History of known liver cirrhosis
- •Presence of jaundice
- •Pregnancy
- •Current breastfeeding
研究组 & 干预措施
Sertraline 400mg
Standard cryptococcal meningitis therapy with amphotericin (0.7-1.0 mg/kg/day) + fluconazole (800-1200mg/day plus adjunctive sertraline therapy at 400mg/day for 2 weeks, then 200mg for 12 weeks, and then tapered over 3 weeks.
干预措施: Sertraline (Drug)
结局指标
主要结局
Survival
时间窗: 18 weeks
18-week survival. The comparison will be between sertraline 400mg group and placebo
次要结局
- Safety (Occurence of Adverse Events)(18 weeks)
- Count of Participants With Cerebrospinal Fluid Sterility(14 days)
- Center for Epidemiologic Studies in Depression (CES-D) Scale(14 weeks)
- Quantitative Neurocognitive Performance Score (QNPZ-8)(14 weeks)
- Fungal Clearance as Determined by Early Fungicidal Activity of CDF(14 days)
- Number of Participants Experiencing IRIS OR Relapse(18 weeks)
- Event Free Survival(18 weeks)