Tuberculous meningitis is a severe brain infection which often causes disability and death even when treated with the best available treatment. Aspirin is a type of anti-inflammation drug which can reduce the inflammatory response in brains of patients with tuberculous meningitis, and therefore may decrease some of the most severe outcomes. This study compares the use of aspirin (at 2 different doses) versus placebo as an additional therapy to the standard treatment to see if aspirin is safe and helpful in reducing disability and death from tuberculous meningitis. Patients will be treated with aspirin or placebo for 60 days and followed up while on standard treatment for 8 months.

The study is a parallel group, double blind, randomised, placebo controlled trial of 60 days treatment with placebo vs. 81mg daily dose vs. 1000mg daily dose aspirin for the treatment of HIV-uninfected adults with tuberculous meningitis.

All patients will receive standard anti-tuberculous chemotherapy and adjunctive dexamethasone, according to Viet Nam National Tuberculosis Programme guidelines. Participants will be stratified by Medical Research Council UK disease severity grade, and randomized at enrollment to one of three study arms (1:1:1 ratio). Patients will be admitted to hospital for at least the first 14 days of study treatment enabling real-time active surveillance of any adverse events after which they will be discharged according to clinical care with continued monitoring.

A schedule of clinical and laboratory monitoring including lumbar puncture, pharmacokinetic assessment of peripheral blood monocyte/macrophage antimicrobial activity, clinical assessments, brain magnetic resonance imaging (MRI) and neurological assessment will manage patient safety and capture study outcomes.

Inclusion Criteria:

• Male or female, aged 18 years or above.
• Suspected TBM and anti-tuberculosis chemotherapy either planned or started
• Less than 3 days of anti-tuberculosis chemotherapy taken for the current infection
• Patient or representative (if the patient is unable) is willing and able to give informed consent for participation in the study.

Exclusion Criteria:

• HIV infection (negative rapid test or Elisa test is required)
• Unlikely, for any reason, to be able to have an MRI brain scan within 5 days (120 hours) of randomisation
• Known or suspected infection with multi-drug resistant tuberculosis (resistant to at least isoniazid and rifampicin)
• Unable to take isoniazid, rifampicin, or pyrazinamide at recommended doses for any reason
• History of diagnosed peptic ulceration or gastro-intestinal bleeding
• Active gastro-intestinal bleeding is suspected
• Taken >1 dose of aspirin (at any dose) or any other non-steroidal anti-inflammatory drugs for any reason within 2 weeks of screening
• Aspirin considered mandatory for any reason by the attending physician
• Aspirin considered to be contraindicated for any reason by the attending physician
• Pregnancy or breast feeding (negative urine pregnancy test for all females of child-bearing age)
• Dexamethasone considered to be contraindicated for any reason by the attending physician
• Any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.