Cyclophosphamide to treat CNS TB related proliferative arachnoiditis not responding to usual medicationsIn our Department, we tried cyclophosphamide in four patients after consent, and found remarkable improvement in all of them. In order to test this, a randomized controlled trial is needed.
- Conditions
- Health Condition 1: G031- Chronic meningitisHealth Condition 2: G01- Meningitis in bacterial diseases classified elsewhere
- Registration Number
- CTRI/2020/11/029276
- Lead Sponsor
- All India Institute of Medical Sciences New Delhi
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 placeboTimepoint: 6 months
- Secondary Outcome Measures
Name Time Method