NEWS
Category : INTENSE-TBM | Date : Nov 8, 2022
8 November 2022 – Study protocol published in TRIALS
Thomas Maitre, Maryline Bonnet, Alexandra Calmy, Mihaja Raberahona, Rivonirina Andry Rakotoarivelo, Niaina Rakotosamimanana, Juan Ambrosioni, José M. Miró, Pierre Debeaudrap, Conrad Muzoora, Angharad Davis, Graeme Meintjes, Sean Wasserman, Robert Wilikinson , Serge Eholié, Frédéric Ello Nogbou, Maria-Camilla Calvo-Cortes, Corine Chazallon, Vanessa Machault, Xavier Anglaret, Fabrice Bonnet.
Background: Tuberculous meningitis (TBM) is the most lethal and disabling form of tuberculosis (TB) particularly in sub-Saharan Africa. Current anti-TB treatment is poorly effective since TBM mortality reaches 40% in HIV negative patients and up to 70% in HIV co-infected patients. To reduce TBM induced morbidity and mortality, the INTENSE-TBM trial evaluates two interventions in both HIV-infected and uninfected patients: an anti-TB treatment intensification using high-dose rifampicin (35 mg/kg daily) and oral linezolid (1,200 mg daily and then 600 mg daily) during the first 8 weeks of the anti-TB treatment and the use of adjunctive aspirin (200 mg daily).
Methods: This is a randomized controlled, phase III, multicenter, 2 x 2 factorial plan superiority trial. The trial has four arms, combining the two experimental treatments (intensified TBM regimen and aspirin) with the two reference treatments (WHO standard TB treatment and placebo) and is open-label for anti-TB treatment and double blind placebo-controlled for aspirin treatment. This trial is conducted in adult or adolescent of age ≥15 years with TBM defined as “definite”, “probable” or “possible” using Tuberculosis Meningitis International Research Consortium criteria, in four African countries: Ivory Coast, Madagascar, Uganda and South Africa. The primary outcome is all-cause death between inclusion and week 40.
Discussion: The INTENSE-TBM trial represents a key opportunity to enhance TBM treatment with widely available existing drugs notably in high incidence setting of both TB and HIV. The trial design is pragmatic and the results will permit early and effective applications in TBM patients care, in both HIV and TB high incidence countries.
Trial registration: ClinicalTrials.gov, ID: NCT04145258
