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We hypothesised that aspirin prevents TBM-related brain infarction through its anti-thrombotic, anti-inflammatory, and pro-resolution properties. We conducted a randomised controlled trial in HIV-uninfected adults with TBM of daily aspirin 81 mg or 1000 mg, or placebo, added to the first 60 days of anti-tuberculosis drugs and dexamethasone (NCT02237365). The primary safety endpoint was gastro-intestinal or cerebral bleeding by 60 days; the primary efficacy endpoint was new brain infarction confirmed by magnetic resonance imaging or death by 60 days. Secondary endpoints included 8-month survival and neuro-disability; the number of grade 3 and 4 and serious adverse events; and cerebrospinal fluid (CSF) inflammatory lipid mediator profiles. 41 participants were randomised to placebo, 39 to aspirin 81 mg\/day, and 40 to aspirin 1000 mg\/day between October 2014 and May 2016. TBM was proven microbiologically in 92\/120 (76.7%) and baseline brain imaging revealed \u22651 infarct in 40\/114 (35.1%) participants. The primary safety outcome occurred in 5\/36 (13.9%) given placebo, and in 8\/35 (22.9%) and 8\/40 (20.0%) given 81 mg and 1000 mg aspirin, respectively (p=0.59). The primary efficacy outcome occurred in 11\/38 (28.9%) given placebo, 8\/36 (22.2%) given aspirin 81 mg, and 6\/38 (15.8%) given 1000 mg aspirin (p=0.40). Planned subgroup analysis showed a significant interaction between aspirin treatment effect and diagnostic category (P\n                    <jats:sub>heterogeneity<\/jats:sub>\n                    = 0.01) and suggested a potential reduction in new infarcts and deaths by day 60 in the aspirin treated participants with microbiologically confirmed TBM (11\/32 (34.4%) events in placebo vs. 4\/27 (14.8%) in aspirin 81 mg vs. 3\/28 (10.7%) in aspirin 1000 mg; p=0.06). CSF analysis demonstrated aspirin dose-dependent inhibition of thromboxane A\n                    <jats:sub>2<\/jats:sub>\n                    and upregulation of pro-resolving CSF protectins. The addition of aspirin to dexamethasone may improve outcomes from TBM and warrants investigation in a large phase 3 trial.\n                  <\/jats:p>","DOI":"10.7554\/elife.33478","type":"journal-article","created":{"date-parts":[[2018,2,26]],"date-time":"2018-02-26T19:00:18Z","timestamp":1519671618000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.33478","source":"Crossref","is-referenced-by-count":125,"title":["A randomised double blind placebo controlled phase 2 trial of adjunctive aspirin for tuberculous meningitis in HIV-uninfected adults"],"prefix":"10.7554","volume":"7","author":[{"given":"Nguyen TH","family":"Mai","sequence":"first","affiliation":[{"name":"Oxford University Clinical Research Unit","place":["Ho Chi Minh City, Vietnam"]},{"name":"Hospital for Tropical Diseases","place":["Ho Chi Minh City, Vietnam"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Dobbs","sequence":"additional","affiliation":[{"name":"Western General 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