CTRI/2020/11/029276招募中2/3 期
Efficacy and safety of Cyclophosphamide in the treatment of refractory proliferative arachnoiditis in Central nervous system Tuberculosis - A Randomized double blinded placebo controlled Trial
All India Institute of Medical Sciences New Delhi1 个研究点 分布在 1 个国家目标入组 40 人开始时间: 2020年11月30日最近更新:
试验速览
- 阶段
- 2/3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- To compare the proportion of patients who attain functional independence (mRS 0-2) 6 months after cyclophosphamide therapy for proliferative arachnoiditis refractory to corticosteroids and standard Anti-tubercular therapy in CNS tuberculosis to those who receive placebo
研究概览
简要总结
Tubercular meningitis occurs in around 10% of those with extrapulmonary tuberculosis and is a major cause of mortality and morbidity. Inspite of effective Anti-tubercular drugs, still around 30% of patients develop complications due to arachnoiditis such as spinal tubercular radiculomyelitis, optico-chiasmatic arachnoiditis, development of new tuberculomas after starting therapy etc. which are probably immune mediated inflammatory responses due to paradoxical reaction to ATT.
The management of arachnoiditis is far from satisfactory. High dose methylprednisolone, intrathecal hyaluronic acid, thalidomide have been tried in small case series and case reports. However, the results have not been satisfactory.
There are two published reports of cyclophosphamide usage in TBM related vasculitis and stroke
In our Department, the investigators tried cyclophosphamide in four patients after consent, and found remarkable improvement in all of them. (Under peer review) In order to test this hypothesis, a randomized controlled trial is needed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified block randomization
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 14.00 Year(s) 至 60.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Patients attending Neurology/Pulmonary Medicine/Medicine/Geriatric Medicine OPD/admitted in respective wards with proliferative tubercular arachnoiditis refractory to corticosteroids and standard Anti-tubercular drugs for CNS tuberculosis 2.Atleast 14 years of age of all sexes 3.Not more than 60 years of age at time of enrolment 4.Patient was started on ATT for tubercular meningitis and had clearcut clinical improvement with resolution of fever/constitutional symptoms AND improvement in headache, vomiting and sensorium for atleast 10 days following which there is deterioration again due to arachnoiditis 5.Developed paraparesis/quadriparesis/sphincter dysfunction due to spinal radiculomyelitis OR vision loss due to due to optico-chiasmatic arachnoiditis with imaging evidence of arachnoiditis 6.Has received standard ATT for atleast 3 months with adequate dose and compliance 7.Received corticosteroids for treatment of arachnoiditis and deemed to be refractory to corticosteroids by the primary physician treating the patient 8.MRI brain and spine are suggestive of Arachnoiditis 9.CSF GeneXpert/Line Probe assay/cultures are not suggestive of drug resistant tuberculosis 10.Reasonable clinical certainty OR allied investigations such as CECT chest/abdomen/PET CT ruling out drug resistant tuberculosis 11.Other relevant investigations like CSF analysis not suggestive of alternative diagnosis such as cysticercal/ cryptococcal/other fungal infections/other causes of chronic meningitis such as brucella/ nocardia/ syphilis/recurrent viral meningitis/ carcinomatous/ lymphomatous meningitis or non infective causes such as sarcoidoisis/sub-arachnoid hemorrhage etc.
- •12.Willing to undergo periodic assessment clinically and with MRI.
- •13.Ready to provide consent for cyclophosphamide therapy 14.Willing to adhere to protocol and comply with follow up visits.
排除标准
- •1.Not willing to provide consent 2.Not willing to adhere to protocol 3.Developed significant drug induced liver dysfunction so that patient is not being given Rifampicin, INH or pyrazinamide and is on modified ATT including quinolones, ethambutol and aminoglycosides or second line drugs only in the absence of Rifampicin and INH 4.Drug resistant tubeculosis 5.Men and Women of childbearing potential who are not using adequate contraception or women who are pregnant and lactating 6.Patients who are on immunosuppressants such as cyclophosphamide/ azathioprine/ methotrexate/MMF/ calcineurin inhibitors for autoimmune conditions/post transplantation or chemotherapy for any systemic malignancy 7.HBsAg, HIV serology and anti HCV positive 8.Having life threatening infections such as pneumonia/urosepsis 9.Patients who have developed large artery strokes with significant brain parenchymal damage 10.Patients with expected life expectancy less than 1 year due to primary disease or comorbidity based on clinical prediction scores for specific disease 11.Patients with systemic malignancy within the last 5 years 12.Known allergy to cyclophosphamide or its preservatives/excipients 13.Receiving cyclophosphamide for any indication in the last 12 weeks 14.Gross hematuria prior to enrolment to the study/USG features of hemorrhagic cystitis 15.Cytopenias Hct <25%, TLC<4000/mm3 or Platelet count <1,20,000/mm3 at the time of enrolment 16.Alanine amino transferase (ALT) > 3 upper limit of normal at time of enrolment.
结局指标
主要结局
To compare the proportion of patients who attain functional independence (mRS 0-2) 6 months after cyclophosphamide therapy for proliferative arachnoiditis refractory to corticosteroids and standard Anti-tubercular therapy in CNS tuberculosis to those who receive placebo
时间窗: 6 months
次要结局
- To compare the proportion of patients who attain independent ambulation 6 months after cyclophosphamide therapy for proliferative arachnoiditis refractory to corticosteroids and standard Anti-tubercular therapy in CNS tuberculosis to those who receive placebo.(6 months)
- To compare the proportion of patients who attain atleast 2 points improvement on Snellen’s chart in visual acuity 6 months after cyclophosphamide therapy for proliferative arachnoiditis refractory to corticosteroids and standard Anti-tubercular therapy in CNS tuberculosis to those who receive placebo.(6 months)
- Comparing Global patient well being as assessed by SF-36 pre and 6 months post cyclophosphamide therapy(6 months)
- Occurrence of life threatening infections necessitating cessation of therapy upto 3 months post cyclophosphamide therapy(3 months)
- Occurrence of infections needing hospitalization or intravenous antibiotic/antiviral/anti-fungal therapy upto 3 months post cyclophosphamide therapy(3 months)
- To compare proportion of patients who attain atleast two point improvement on a semiquantitative visual acuity measurement in those who have visual acuity less than 1/60 on snellen’s chart (finger counting at 1 m, hand movements at 1 m, perception of light, no perception of light considered as discrete points below 1/60 vision on standard Snellen’s chart) 6 months after cyclophosphamide therapy(6 months)
- To compare the proportion of patients improving from mRS ≥3 to mRS ≤2 six months post cyclophosphamide therapy(6 months)
- Shift analysis pre-and 6 months post therapy in terms of change in mRS(6 months)
- To compare proportion of patients improving from visual acuity of 3/60 in the better eye to 3/60 or more 6 months post cyclophosphamide therapy(6 months)
- Flare up of underlying tuberculosis upto 3 months post cyclophosphamide therapy(3 months)
- To compare the proportion of patients who attain improvement in bladder/bowel function 6 months after cyclophosphamide therapy for proliferative arachnoiditis refractory to corticosteroids and standard Anti-tubercular therapy in CNS tuberculosis to those who receive placebo(6 months)
- Occurrence of Grade III cytopenias defined as per common terminology criteria for adverse events v 5.0 upto 6 weeks post cyclophosphamide therapy(6 weeks)
- Grade III transaminitis as per CTCAE v 5.0 upto 6 weeks post cyclophosphamide therapy(6 weeks)
- Occurrence of hemorrhagic cystitis upto 2 weeks post cyclophosphamide therapy(2 weeks)
- Any other significant adverse effect(12 weeks)
研究者
研究点 (1)
Loading locations...
相似试验
尚未招募
2 期
Cyclophosphamide in the Treatment of Refractory Proliferative Arachnoiditis in CNS TuberculosisTubercular MeningitisArachnoiditis; Tuberculous (Etiology)TuberculosisNCT04620772All India Institute of Medical Sciences, New Delhi40
已完成
2 期
Rifampicin Explorative PK Study for Tuberculous Meningitis Comparing Oral and Intravenous PreparationTuberculous MeningitisNCT01802502Universitas Padjadjaran30
已完成
2 期
Pharmacokinetic Study of Linezolid for TB MeningitisTuberculosis, MeningealLinezolidNCT03537495Universitas Padjadjaran36
已完成
不适用
Intrathecal Therapy for Adult Tuberculous Meningitis: Impact on Clinical OutcomesTuberculous MeningitisNCT06811792Beijing Chest Hospital837
已完成
2 期
A Pilot Study of Adjunctive Aspirin for the Treatment of HIV Negative Adults With Tuberculous MeningitisTuberculous MeningitisNCT02237365Oxford University Clinical Research Unit, Vietnam120