INTENSE-TBM is randomized controlled, phase III, multicenter, 2 x 2 factorial plan superiority trial assessing the efficacity of two interventions to reduce mortality from tuberculous meningitis (TBM) in adolescents and adults with or without HIV-infection in sub-Saharan Africa:
* Intensified TBM treatment with high-dose rifampicin and linezolid, compared to WHO standard TBM treatment. * Aspirin, compared to not receiving aspirin. The trial will be open-label for anti-TB treatment and placebo-controlled for aspirin treatment.
Age ≥ 15 years
TBM defined as "definite", "probable" or "possible"
Signed Informed Consent
Definite TBM = at least one of the following criteria: acid-fast bacilli seen in CSF microscopy, positive CSF M. tuberculosis culture, or positive CSF M. tuberculosis commercial nucleic acid amplification test.
> 5 days of TB treatment
Renal failure (eGFR<30 ml/min, CKD-EPI formula).
Neutrophil count < 0.6 x 109/L.
Hemoglobin concentration < 8 g/dL.
Factorial
Aspirin
DrugTwo tablets of aspirin 100 mg per day from inclusion (D-0) to end of Week-8 (W-8)
Placebo of aspirin
DrugTwo placebo tablets with the same appearance of aspirin 100 mg per day from inclusion (D-0) to end of Week-8 (W-8)
WHO TBM treatment
Drug2 months of (R-H-Z-E) + 7 months of (R-H)
Intensified TBM treatment
Drug2 months of (HDR-L-H-Z-E) + 7 months of (R-H), with HDR=high-dose rifampicin and L=linezolid
Rate of all-cause death
Rate of all-cause death
Rate of all-cause death or loss to follow-up
Rate of new central neurological event or aggravation of a central neurological event existing at baseline
Rate of grade 3-4 adverse events (DAIDS adverse events grading table)
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ANRS, Emerging Infectious Diseases
Lead sponsor
European Union
Collaborator
European and Developing Countries Clinical Trials Partnership (EDCTP)
Collaborator