Phase III Trial of Intensified Tuberculosis Treatment and Aspirin to Reduce Death in Adolescents and Adults With Tuberculous Meningitis in Sub-Saharan Africa

What this Trial Is About

Researchers are conducting a phase III randomized controlled trial called INTENSE-TBM to evaluate treatments aimed at reducing death rates in adolescents and adults with tuberculous meningitis, including those with or without HIV infection in sub-Saharan Africa. The trial compares intensified tuberculosis meningitis treatment using high-dose rifampicin and linezolid against the World Health Organizations standard treatment, and also examines the effects of aspirin compared to a placebo. This study is carried out across multiple countries including Cte dIvoire, Madagascar, Uganda, and South Africa. Participants are randomly assigned to one of four groups standard WHO tuberculosis meningitis treatment with aspirin placebo, standard treatment with aspirin, intensified treatment with aspirin placebo, or intensified treatment with aspirin. The intensified treatment includes high doses of rifampicin and linezolid for the first eight weeks, followed by standard doses of rifampicin and isoniazid until week 40. Aspirin or placebo is taken daily during the first eight weeks. After week 8, all participants continue with standard treatment until week 40. During the 40-week follow-up, participants undergo regular assessments to monitor survival, neurological events, adverse effects, and disability. Laboratory tests, including culture and drug resistance evaluations, as well as pharmacokinetic studies in subsets of patients, are conducted. HIV-infected participants will have additional monitoring of AIDS-related illnesses, viral load, and immune cell counts. The primary outcome measures the rate of death from any cause up to 40 weeks, with secondary outcomes assessing safety, effectiveness, and quality of life related factors.

Intensified Tuberculosis Treatment to Reduce the Mortality of Patients With Tuberculous Meningitis