About this trial
Tuberculous meningitis (TBM) is the most lethal form of extra pulmonary tuberculosis. This devastating disease kills almost a third of its sufferers and disables a significant proportion of the survivors. TBM poses one of the most difficult diagnostic and therapeutic challenges in modern clinical practice. High-quality robust clinical trials have made a considerable contribution to the treatment of pulmonary tuberculosis in the last four decades. However, evidence from such clinical trials is lacking in TBM and the treatment remains uncertain. There is a significant variation in the choice, dose and duration of drugs between countries, institutions and clinicians. Investigators propose a multi-centric open-label clinical trial to assess the efficacy of short-course anti-TB drugs with high dose rifampicin, and moxifloxacin along with conventional anti-TB drugs and adjuvant therapy with aspirin and corticosteroids. Controls will receive standard treatment as per national guidelines for TBM. The investigators also aim to assess the safety and tolerability of high-dose Rifampicin and Moxifloxacin and the Pharmacodynamics and Pharmacokinetics parameters of ATT (Rifampicin, INH, Moxifloxacin and Pyrazinamide) in CSF between the two groups
Eligibility criteria
Qualifiers
Adults (> 18 years) with or without HIV infection
Possible, probable or definite TBM according to Lancet consensus diagnostic criteria
Willing to give written informed consent
Is willing to have an HIV test.
Disqualifiers
Known current/previous drug resistance to ATT (Rifampicin, INH, FQ)**
Concurrent or known diagnosis any other meningitis such as bacterial, viral, and fungal.
Currently having an uncontrolled cardiac arrhythmia or ECG abnormalities which are contradiction for the administration of moxifloxacin including prolonged QTc. QTc value define as >450 ms in males and >460 ms in females measured in lead II or V5 on a standard 12-lead ECG.
Has clinical icterus or hepatic impairment characterized by serum bilirubin level above the normal laboratory reference range with abnormal liver enzymes, or isolated alanine aminotransferase (ALT) and/ or aspartate aminotransferase (AST) levels above 5 times the upper limit of the normal laboratory reference range
Trial design
Treatments tested in this trial
- High dose rifampicin (25mg/kg)
- Moxifloxacin 400mg
- Aspirin 150 mg
- Isoniazid
- Pyrazinamide
- Steroid
- Rifampicin
- HRZE
- HRE
Treatment groups
Sponsors and collaborators
Indian Council of Medical Research
Lead sponsor
Tuberculosis Research Centre, India
Sponsor institution
All India Institute of Medical Sciences, Jodhpur
Collaborator
Christian Medical College, Vellore, India
Collaborator
Jawaharlal Institute of Postgraduate Medical Education & Research
Collaborator
North Eastern Indira Gandhi Regional Institute of Health ans Medical Sciences
Collaborator
Madras Medical College
Collaborator
Rural Development Trust Hospital
Collaborator