In tuberculous meningitis (TBM), a common functional promoter variant (C/T transition) in the gene encoding leukotriene A4 hydrolase (LTA4H) predicts pre-treatment inflammatory phenotype and response to dexamethasone in HIV-uninfected individuals.
How dexamethasone, as an adjunctive anti-inflammatory treatment, can improve survival in TBM patients, especially in HIV-uninfected individuals, and whether they do so in all patients remain uncertain and is the focus of this trial.
Our primary aim is to determine whether LTA4H genotype, defined at randomisation, determines dexamethasone’s clinical effectiveness when added to the first 6–8 weeks of anti-tuberculosis treatment of TBM.
In making this assessment, we not only determine whether placebo is non-inferior to dexamethasone in patients having LTA4H CT or CC-genotype, in terms of:
Our secondary aim is to investigate alternative management strategies in a subset of patients who develop drug-induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy whenever possible.