Adjunctive Dexamethasone for Cerebral Toxoplasmosis: a Double-blinded Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 138
- 试验地点
- 1
- 主要终点
- Mortality
研究概览
简要总结
Toxoplasma gondii infects over one third of the global human population. Cerebral toxoplasmosis is the most common opportunistic infection in HIV patients resulting in up to 50% of mortality with proper treatment and 80% without it. The fatality mainly due to the brain edema resulted from the mass effect lesion. In addition of anti toxoplasmosis given, adjunctive therapy such as steroid is recommended in order to reduce brain edema, but the dose and duration of administration in cerebral toxoplasmosis has not been evaluated in a clinical trial. Adjunctive therapy given in cerebral toxoplasmosis patients still remains unclear. Moreover, its safety in immunodeficiency cases is still debatable.
详细描述
Steroid produces a raising expression of anti inflammation genes (NF-κB, IκB-α and antagonist receptor IL-1) and inhibits pro inflammation cytokines ( TNF-α and IL-1β). It also works as anti edema by correcting the disrupted blood brain barrier during infection process. Dexamethasone is considered to be chosen in this clinical trial due to the long half life among steroids, the strongest glucocorticoid effect comparing other steroids, and easily prepared and used on daily practice.
There are limited data from using adjunctive steroid for treatment of HIV-associated with cerebral toxoplasmosis. Previous study in France published in 2012 showed steroid did not give any significant improvement for patients' neurological outcome and did not worsen patients' condition such as getting nosocomial infection. Meanwhile comparing previous study by Arens et. al in 2007, there was an increasing mortality rate on adjunctive steroid used in cerebral toxoplasmosis patients.
As result of limited data, our trial is looked forward to answer about the efficacy of dexamethasone treatment in reducing mortality rate of cerebral toxoplasmosis patients.
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
- Double (Participant, Care Provider)
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
- •Age 18 years or above.
- •Clinical signs and symptoms compatible to cerebral toxoplasmosis
- •Serology HIV positive
- •Immunoglobulin G anti-toxoplasma titre is positive
- •One or more mass lesions on the neuroradiological finding
- •None or less than 3 days of dexamethasone therapy taken
- •Written informed consent from the patients or from close relatives of the patient if the patient is unconscious.
排除标准
- •History of anti-toxoplasmosis administrattion for more than 5 days before recruitment
- •Hypersensitivity or other contraindication to dexamethasone
研究组 & 干预措施
Dexamethasone
Sixty nine patients will be administered randomly dexamethasone 20 mg IV for 7 days.
Along with study drug or placebo, patients will receive standard anti toxoplasmosis (Oral pyrimethamine 150 or 200 mg (according to body weight) for three days continued by 50 or 75mg (according to body weight) per day or oral cotrimoxazole 2 x 1920 mg; oral clindamycin 600mg q.i.d) in accordance to national neurologist association guidelines.
干预措施: Dexamethasone (Drug)
Placebo
Sixty nine patients will be administered randomly Normal Saline 0,9% IV (4 cc) for 7 days.
Along with study drug or placebo, patients will receive standard anti toxoplasmosis (Oral pyrimethamine 150 or 200 mg (according to body weight) for three days continued by 50 or 75mg (according to body weight) per day or oral cotrimoxazole 2 x 1920 mg; oral clindamycin 600mg q.i.d) in accordance to national neurologist association guidelines.
干预措施: Placebo (Drug)
结局指标
主要结局
Mortality
时间窗: 90 days
Determined by the time from randomization to death (in days)
次要结局
- Number of participants with grade 3 and 4 and serious adverse events related to study drug(7 days)
- Changes in consciousness(14 days)
- Neurological response (1)(up to 90 days)
- Neuroradiological response(90 days)
- Neurological response (2)(up to 90 days)
- Cognitive function (1)(up to 90 days)
- Cognitive function (2)(up to 90 days)