Neuroprotection With Minocycline Therapy for Acute Stroke Recovery Trial, A Double-Blind, Randomized, Placebo-controlled, Multi-center Study
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 139
- 试验地点
- 1
- 主要终点
- Reduction of neurologic deficits and improvement of functional outcome on day 90 post-stroke
研究概览
简要总结
Background: Stroke is a leading cause of death and chronic serious disability worldwide.
Minocycline, a semisynthetic tetracycline, has consistently been shown in recent years to be neuroprotective in animal models of brain ischemia. Furthermore, a small, open label study done in humans with acute ischemic stroke published late last year showed that minocycline, when administered for 5 days, within 6 to 24 hours after stroke onset was highly effective in improving functional outcome even as early as 7 days after stroke onset. However, further well-conducted, randomized controlled translational studies using minocycline are currently lacking.
Objective: To determine if minocycline, administered within 3 to 48 hours after acute ischemic stroke onset is superior to placebo in reducing neurological deficit and improving functional outcome at 90 days post stroke.
Methods: The investigators plan to do a multi-centre randomized, double-blind, placebo controlled trial in which ischemic stroke patients will be randomized to treatment with either oral minocycline or placebo within 3 to 48 hours of symptom onset. The primary efficacy endpoint will be the modified Rankin scale (mRS) score for all randomized subjects at 90 days.
Secondary endpoints will include improvement of the NIH Stroke Scale (NIHSS) score from baseline and Barthel index at 90 days.
NeuMAST will test the following hypotheses:
Primary Hypothesis: Minocycline, compared with placebo, when administered between 3 to 48 hours after the onset of acute ischemic stroke improves recovery and functional outcome as assessed by mRS scores on day 90 post-stroke.
Secondary Hypotheses:
- Minocycline compared to placebo, when administered between 3 to 48 hours after onset of acute ischemic stroke improves recovery and functional outcome as assessed by improvement of NIHSS score on day 90 post-stroke.
- Minocycline compared to placebo, when administered between 3 to 48 hours after onset of acute ischemic stroke improves functional outcome as assessed by the Barthel Index (BI) score on day 90 post-stroke.
- Minocycline, compared with placebo reduces 90 day risk of recurrent stroke, MI or death when administered between 3 to 48 hours after acute ischemic stroke onset.
A positive result will have a significant impact in the management of acute ischemic stroke and pave the way for future studies aimed at finding the optimal dose and formulation of minocycline for treating acute ischemic stroke.
详细描述
A) Specific Primary Objective:
- To determine if minocycline, administered within 3 to 48 hours of acute ischemic stroke onset is superior to placebo in reducing neurological deficit and improving functional outcome on day 90 post stroke.
B) Specific Secondary Objectives:
- To determine if minocycline administered within 3 to 48 hours of acute ischemic stroke onset is superior to placebo in reducing the 90 day risk of recurrent ischemic stroke, myocardial infarction (MI) and death.
- To study and compare the differential efficacy of minocycline administered as stated above, on the four stroke subtypes according to TOAST criteria, i.e. lacunar stroke, large vessel atherosclerosis, cardioembolic and cryptogenic stroke
C) Primary Efficacy Endpoint:
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
- 21 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Singapore citizens or permanent residents
- •Age range between 21 to 80 years
- •NIHSS equal or more than 5 but less than 22 at time of admission
- •Clinical diagnosis of acute ischemic stroke according to WHO criteria
- •Onset of stroke between 3 to 48 hours prior to start of treatment
- •Must have a working telephone line
排除标准
- •Long term residents of Institutions and Nursing homes
- •Patients with significant baseline cognitive dysfunction
- •Patients with hemorrhagic stroke
- •Pre-stroke MRS more than 1
- •Evidence of other disease of the CNS (i.e., brain tumor, CNS infections)
- •Known allergic response to tetracycline
- •Acute or Chronic renal failure
- •Hepatitis or liver disease
- •Pre-existing infectious disease requiring antibiotics
- •Receipts of IV rTPA
- •Participation in another clinical trial in the preceding 3 months
- •Unable or unwilling to provide inform consent
- •Unwilling to return for frequent clinic visits
- •Geographic or social factors making the study participation impractical
研究组 & 干预措施
matching placebo pill
matching placebo
干预措施: Matched placebo (Drug)
Oral minocycline
Minocycline 200mg
干预措施: Minocycline (Borymycin) (Drug)
结局指标
主要结局
Reduction of neurologic deficits and improvement of functional outcome on day 90 post-stroke
时间窗: 3 months
次要结局
- Reduction of 90 day risk of recurrent ischemic stroke, myocardial infarction and death(3 months)
研究者
Dr. Rajinder Singh
Dr
Singhealth Foundation