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

Inclusion Criteria:

A patient will be eligible for entry to the trial if ALL of the following conditions are satisfied

1. Adults (> 18 years) with or without HIV infection
2. Possible, probable or definite TBM according to Lancet consensus diagnostic criteria
3. Willing to give written informed consent
4. Is willing to have an HIV test.
5. Residing within 100 km of the study sites
6. Express willingness to attend the treatment centre for supervised treatment
7. Express willingness to adhere to the trial procedures and follow-up schedule.
8. Agrees to use effective barrier contraception during the period of the treatment in case of female participants

Exclusion Criteria:

Patients will not be eligible for the trial if they meet ANY of the following criteria

1. Known current/previous drug resistance to ATT (Rifampicin, INH, FQ)**

2. Concurrent or known diagnosis any other meningitis such as bacterial, viral, and fungal.

3. 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.

4. 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

5. Previous history of anti-TB treatment, If any, should not exceed one month in the past and not more than 7 days in the preceding one month.

6. pregnant or lactating women

7. rapid clinical deterioration or very sick and moribund during the screening process, renal failure, liver disease or any condition (social or medical) that in the opinion of the investigator would make trial participation unreliable or unsafe.

8. Has a known allergy to any of the drugs proposed to be used in the trial regimen

   • All participants with Rifampicin resistance will be excluded at baseline from the study. Participants with H, FQ and Z resistance identified from MGIT results done at baseline will be referred back to NTEP for appropriate management and their numbers will be compensated.