Study of efficacy of thalidomide in complicated tubercular infection of central nervous system
试验速览
- 阶段
- 2/3 期
- 状态
- 招募中
- 入组人数
- 126
- 试验地点
- 1
- 主要终点
- Primary outcome – Mortality at 6 months of intervention.
研究概览
简要总结
Tuberculosis (TB) caused by Mycobacterium tuberculosis (M.tb) continues to be a major public health challenge. According to the Global tuberculosis report 2022 by WHO, an estimated 10.6 million fell ill with TB in 2021 with 1.6 million people succumbing to the disease (1). 5-15% of all cases of TB affect extrapulmonary sites; and 1% of all cases infect the central nervous system (CNS) (2,3). Whilst the overall percentage of infliction of the CNS is small, it causes much more morbidity and mortality. TB is known to affect the meninges of the brain leading to tubercular meningitis (TBM) and can also infect the spinal cord, and the parenchyma.
The optimal management of TBM remains unresolved. Much of the morbidity and mortality caused in a case of infection of nervous system is due to dysregulated immune response. Immunomodulation is thus maybe useful in the management of patients who suffer from immune mediated complications.
Presently only corticosteroids are approved for the treatment of TBM along with anti-tubercular drugs. An analysis from nine trials have shown that steroids reduce mortality from tuberculous meningitis, at least in the short term (4). Corticosteroids may have no effect on the number of people who survive tuberculous meningitis with disabling neurological deficit, but this outcome is less common than death. However even with the concomitant use of corticosteroids the morbidity and mortality continue to be high.
Accumulating evidence throws light on the role of various cytokines in the pathogenesis of exaggerated immune response to M.tb. Tumor necrosis factor alpha (TNF- α) is essential to control M.tb replication, however increased concentration leads to severe tissue damage (5). Thalidomide, which is approved for use in erythema nodosum leprosum decreases TNF- α production in a dose dependent manner (6). Observational studies have shown potential benefit of thalidomide in treatment of TBM with early clinical and radiological resolution of disease.
Data from randomized controlled trial (RCT) regarding the efficacy of thalidomide in TBM and CNS TB is lacking. We aim to conduct a RCT to study the efficacy of thalidomide in TBM.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Outcome Assessor Blinded
入排标准
- 年龄范围
- 14.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Possible, probable, or definite TBM as diagnosed by Marais et al criteria.
- •Patients already on standard ATT and steroid protocol for CNS TB who develop complications in the form of paradoxical worsening like opto-chiasmatic syndrome, spinal arachnoiditis, increase in tuberculomas, exudates or clinical worsening etc.
排除标准
- •1.Patients who are either HIV positive or immunocompromised due to some other disease.
- •2.Patients are on immunosuppressive drugs.
- •3.Patients who cannot undergo lumbar puncture or MRI examination.
- •4.Pregnant patients.
- •5.CSF gram stain or/and culture showing microorganisms other than acid fast bacilli.
结局指标
主要结局
Primary outcome – Mortality at 6 months of intervention.
时间窗: Primary outcome – Mortality at 6 months of intervention. | Secondary outcome – | •Clinical improvement | oFunctional status – mRS scale. | oVision – Grading of Visual Acuity | •Radiological improvement | oExudates – Present or absent. | oTuberculomas – Number | oInfarct – Present or absent. | oHydrocephalus – Present or absent. | •Presence of neurological deficit | •Side effects of thalidomide
oVision – Grading of Visual Acuity
时间窗: Primary outcome – Mortality at 6 months of intervention. | Secondary outcome – | •Clinical improvement | oFunctional status – mRS scale. | oVision – Grading of Visual Acuity | •Radiological improvement | oExudates – Present or absent. | oTuberculomas – Number | oInfarct – Present or absent. | oHydrocephalus – Present or absent. | •Presence of neurological deficit | •Side effects of thalidomide
•Radiological improvement
时间窗: Primary outcome – Mortality at 6 months of intervention. | Secondary outcome – | •Clinical improvement | oFunctional status – mRS scale. | oVision – Grading of Visual Acuity | •Radiological improvement | oExudates – Present or absent. | oTuberculomas – Number | oInfarct – Present or absent. | oHydrocephalus – Present or absent. | •Presence of neurological deficit | •Side effects of thalidomide
oExudates – Present or absent.
时间窗: Primary outcome – Mortality at 6 months of intervention. | Secondary outcome – | •Clinical improvement | oFunctional status – mRS scale. | oVision – Grading of Visual Acuity | •Radiological improvement | oExudates – Present or absent. | oTuberculomas – Number | oInfarct – Present or absent. | oHydrocephalus – Present or absent. | •Presence of neurological deficit | •Side effects of thalidomide
Secondary outcome –
时间窗: Primary outcome – Mortality at 6 months of intervention. | Secondary outcome – | •Clinical improvement | oFunctional status – mRS scale. | oVision – Grading of Visual Acuity | •Radiological improvement | oExudates – Present or absent. | oTuberculomas – Number | oInfarct – Present or absent. | oHydrocephalus – Present or absent. | •Presence of neurological deficit | •Side effects of thalidomide
•Clinical improvement
时间窗: Primary outcome – Mortality at 6 months of intervention. | Secondary outcome – | •Clinical improvement | oFunctional status – mRS scale. | oVision – Grading of Visual Acuity | •Radiological improvement | oExudates – Present or absent. | oTuberculomas – Number | oInfarct – Present or absent. | oHydrocephalus – Present or absent. | •Presence of neurological deficit | •Side effects of thalidomide
oFunctional status – mRS scale.
时间窗: Primary outcome – Mortality at 6 months of intervention. | Secondary outcome – | •Clinical improvement | oFunctional status – mRS scale. | oVision – Grading of Visual Acuity | •Radiological improvement | oExudates – Present or absent. | oTuberculomas – Number | oInfarct – Present or absent. | oHydrocephalus – Present or absent. | •Presence of neurological deficit | •Side effects of thalidomide
oTuberculomas – Number
时间窗: Primary outcome – Mortality at 6 months of intervention. | Secondary outcome – | •Clinical improvement | oFunctional status – mRS scale. | oVision – Grading of Visual Acuity | •Radiological improvement | oExudates – Present or absent. | oTuberculomas – Number | oInfarct – Present or absent. | oHydrocephalus – Present or absent. | •Presence of neurological deficit | •Side effects of thalidomide
•Side effects of thalidomide
时间窗: Primary outcome – Mortality at 6 months of intervention. | Secondary outcome – | •Clinical improvement | oFunctional status – mRS scale. | oVision – Grading of Visual Acuity | •Radiological improvement | oExudates – Present or absent. | oTuberculomas – Number | oInfarct – Present or absent. | oHydrocephalus – Present or absent. | •Presence of neurological deficit | •Side effects of thalidomide
oInfarct – Present or absent.
时间窗: Primary outcome – Mortality at 6 months of intervention. | Secondary outcome – | •Clinical improvement | oFunctional status – mRS scale. | oVision – Grading of Visual Acuity | •Radiological improvement | oExudates – Present or absent. | oTuberculomas – Number | oInfarct – Present or absent. | oHydrocephalus – Present or absent. | •Presence of neurological deficit | •Side effects of thalidomide
oHydrocephalus – Present or absent.
时间窗: Primary outcome – Mortality at 6 months of intervention. | Secondary outcome – | •Clinical improvement | oFunctional status – mRS scale. | oVision – Grading of Visual Acuity | •Radiological improvement | oExudates – Present or absent. | oTuberculomas – Number | oInfarct – Present or absent. | oHydrocephalus – Present or absent. | •Presence of neurological deficit | •Side effects of thalidomide
•Presence of neurological deficit
时间窗: Primary outcome – Mortality at 6 months of intervention. | Secondary outcome – | •Clinical improvement | oFunctional status – mRS scale. | oVision – Grading of Visual Acuity | •Radiological improvement | oExudates – Present or absent. | oTuberculomas – Number | oInfarct – Present or absent. | oHydrocephalus – Present or absent. | •Presence of neurological deficit | •Side effects of thalidomide
次要结局
- •Clinical improvement(oFunctional status – mRS scale.)