A Pilot Phase II Randomized Controlled Double Blind Trial of 81mg Aspirin Daily vs. 1000 mg Aspirin Daily vs. Placebo as Adjunctive Therapy in HIV Negative Adults With Tuberculous Meningitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Number of episodes of either cerebral bleeding or clinically significant upper-gastro-intestinal bleeding (composite endpoint)
研究概览
简要总结
Tuberculous meningitis is a severe brain infection which often causes disability and death even when treated with the best available treatment. Aspirin is a type of anti-inflammation drug which can reduce the inflammatory response in brains of patients with tuberculous meningitis, and therefore may decrease some of the most severe outcomes. This study compares the use of aspirin (at 2 different doses) versus placebo as an additional therapy to the standard treatment to see if aspirin is safe and helpful in reducing disability and death from tuberculous meningitis. Patients will be treated with aspirin or placebo for 60 days and followed up while on standard treatment for 8 months.
详细描述
The study is a parallel group, double blind, randomised, placebo controlled trial of 60 days treatment with placebo vs. 81mg daily dose vs. 1000mg daily dose aspirin for the treatment of HIV-uninfected adults with tuberculous meningitis.
All patients will receive standard anti-tuberculous chemotherapy and adjunctive dexamethasone, according to Viet Nam National Tuberculosis Programme guidelines. Participants will be stratified by Medical Research Council UK disease severity grade, and randomized at enrollment to one of three study arms (1:1:1 ratio). Patients will be admitted to hospital for at least the first 14 days of study treatment enabling real-time active surveillance of any adverse events after which they will be discharged according to clinical care with continued monitoring.
A schedule of clinical and laboratory monitoring including lumbar puncture, pharmacokinetic assessment of peripheral blood monocyte/macrophage antimicrobial activity, clinical assessments, brain magnetic resonance imaging (MRI) and neurological assessment will manage patient safety and capture study outcomes.
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
- •Male or female, aged 18 years or above.
- •Suspected TBM and anti-tuberculosis chemotherapy either planned or started
- •Less than 3 days of anti-tuberculosis chemotherapy taken for the current infection
- •Patient or representative (if the patient is unable) is willing and able to give informed consent for participation in the study.
排除标准
- •HIV infection (negative rapid test or Elisa test is required)
- •Unlikely, for any reason, to be able to have an MRI brain scan within 5 days (120 hours) of randomisation
- •Known or suspected infection with multi-drug resistant tuberculosis (resistant to at least isoniazid and rifampicin)
- •Unable to take isoniazid, rifampicin, or pyrazinamide at recommended doses for any reason
- •History of diagnosed peptic ulceration or gastro-intestinal bleeding
- •Active gastro-intestinal bleeding is suspected
- •Taken >1 dose of aspirin (at any dose) or any other non-steroidal anti-inflammatory drugs for any reason within 2 weeks of screening
- •Aspirin considered mandatory for any reason by the attending physician
- •Aspirin considered to be contraindicated for any reason by the attending physician
- •Pregnancy or breast feeding (negative urine pregnancy test for all females of child-bearing age)
- •Dexamethasone considered to be contraindicated for any reason by the attending physician
- •Any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.
研究组 & 干预措施
81mg aspirin
Aspirin 81mg daily for 60 days
干预措施: 81mg aspirin (Drug)
1000mg aspirin
Aspirin 1000mg daily for 60 days
干预措施: 1000mg aspirin (Drug)
Placebo
Visually matched placebo daily for 60 days
干预措施: Placebo (Drug)
结局指标
主要结局
Number of episodes of either cerebral bleeding or clinically significant upper-gastro-intestinal bleeding (composite endpoint)
时间窗: 60 days
Primary Safety Endpoint: Number of episodes of: 1. Cerebral bleeding confirmed by brain imaging and/or 2. Clinically significant upper-gastro-intestinal bleeding, defined as: a) Vomiting fresh or changed blood of any volume; b) Melena; c) Unexplained drop in haemoglobin concentration of \>2g/L or; d) Greater than 5mls of fresh or changed blood aspirated from nasogastric tube
Number of episodes of MRI-proven brain infarction or death (composite endpoint)
时间窗: 60 days
Primary Efficacy Endpoint: Number of episodes of 1. MRI-proven brain infarction and/or 2. Death
次要结局
- Time to death(240 days)
- Number of grade 3&4 and serious adverse events(60 days)
- Duration of hospital stay(240 days)
- Neurological disability score(240 days)
- Resolution of cerebrospinal fluid (CSF) inflammation(30 days)
- Antimicrobial activity of peripheral blood monocyte/macrophages(240 days)
- Proportion of patients with MRI-proven brain infarction(240 days)