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

Recruiting now · Phase 3 · Has a placebo group

Conditions studied: Tuberculous Meningitis

In brief

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.

Key facts

Study ID

NCT04145258

Run by

ANRS, Emerging Infectious Diseases

People needed

768

Starts

2021-02-07

Expected to finish

2026-09-26

Last updated by the study team

2026-06-24

Who can join

Age: 15 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• Probable TBM = total modified Marais score ≥12 when neuroimaging is available, or ≥10 when neuroimaging is not available (at least 2 points should come from CSF or cerebral imaging criteria).
• Possible TBM = total modified Marais 6-11 when neuroimaging is available, or 6-9 when neuroimaging is not available.

You may not qualify if…

• > 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.
• Total bilirubin > 2.6 times the Upper Limit of Normal
• Platelet count < 50 x 109/L.
• ALT > 5 times the Upper Limit of Normal.
• Clinical evidence of liver failure or decompensated cirrhosis.
• For women: more than 17 weeks pregnancy or breastfeeding.
• For patients without decrease level of consciousness (Glasgow Coma Scale = 15): Peripheral neuropathy scoring Grade 3 or above on the Brief Peripheral Neuropathy Score (BPNS).
• Documented M. tuberculosis resistance to rifampicin.
• Positive gram-stain, bacterial culture or cryptococcal antigen in the Cerebral Spinal Fluid.
• Evidence of active bleeding (hemoptysis, gastrointestinal bleeding, hematuria, intracranial bleeding).
• Inability to collect Cerebral Spinal Fluid, except for patients with confirmed tuberculosis (by rapid molecular test or culture) from another biological sample and clinical and/or CT scan evidence of meningitis.
• Major surgery within the last two weeks prior to inclusion.
• Ongoing chronic aspirin treatment (eg for cardiovascular risk).
• Current use of drugs contraindicated with study drugs and that cannot be safely stopped (see Appendix 1: Drugs contra-indicated with study drugs).
• In available history from patients:
• Evidence of past intracranial bleeding.
• Evidence of past of peptic ulceration.
• Evidence of recent (< 3 month) gastrointestinal bleeding.
• Known hypersensitivity contraindicating the use of study drugs .
• Evidence of porphyria.
• Evidence of hyperuricemia or gout.
• Any reason which at the discretion of the investigator would compromise safety and cooperation in the trial.

Where it is running

• Regional Reference Hospital of Kabale — Mbarara, Uganda (enrolling)
• Treichville University Hospital — Abidjan, Côte d’Ivoire (enrolling)
• Dora Nginza Hospital — Port Elizabeth, South Africa (enrolling)
• Livingstone and PE Central Hospitals — Port Elizabeth, South Africa (enrolling)
• Mbarara Regional Reference Hospital — Mbarara, Uganda (enrolling)
• University Hospital Joseph Raseta Befelatanana — Antananarivo, Madagascar (enrolling)
• University Hospital Tambohobe — Fianarantsoa, Madagascar (enrolling)
• Kayelitsha District Hospital — Cape Town, South Africa (enrolling)
• Mitchells Plain Hospital — Cape Town, South Africa (enrolling)
• New Somerset Hospital — Cape Town, South Africa (enrolling)
• Yopougon University Hospital — Abidjan, Côte d’Ivoire
• Morafeno University Hospital — Toamasina, Madagascar
• Cocody University Hospital — Abidjan, Côte d’Ivoire

Full record on ClinicalTrials.gov

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