INTENSE-TBM-2 · Intensified tuberculosis treatment to reduce the high mortality of tuberculous meningitis in HIV-infected and uninfected patients

Tuberculosis (TB) remains a global health problem. The most lethal and disabling form of TB is tuberculous meningitis (TBM), with an estimated 100,000 new cases occurring per year. In sub-Saharan Africa, TBM mortality reaches 40% in HIV negative patients and up to 70% in HIV co-infected patients. Since decades, TBM treatment is based on a regimen used against pulmonary TB, which probably results in suboptimal drug levels in the cerebrospinal fluid (CSF). The main objective of INTENSE-TBM is to reduce the mortality and neurological complications of TBM in adults with or without HIV co-infection in sub-Saharan Africa (SSA). This is investigated via a multicentre randomised multicentre Phase III clinical trial involving 768 patients in four SSA countries to evaluate the efficacy of an intensified TB treatment regimen during the first two months of TB treatment, including high-dose rifampicin and linezolid (repurposed drug), with the addition of aspirin (not as yet authorized for TBM). This intensified TB treatment is expected to reduce mortality by at least 30% for each of the interventions and minimize neurological sequalae. The INTENSE-TBM trial is the largest ongoing trial in the field of TBM worldwide. If superiority of this experimental arm is demonstrated in terms of reduced mortality, it will become the first Phase III study to demonstrate survival benefit from intensified TBM treatment. As per the expected outcomes of this EDCTP-3 call, INTENSE-TBM-2, as the continuation of INTENSE-TBM, a clinical trial funded by EDCTP2 and whose activities were disrupted during the COVID-19 pandemic, aims at concluding the ongoing activities of the EDCTP-2 project. It also aims at complying with ethical issues, such as fully validating the willingness of trial participants to take part in the clinical investigations.