Intensified treatment for tuberculous meningitis to reduce mortality

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This trial evaluates the effectiveness of intensified treatment for tuberculous meningitis (TBM) using high-dose rifampicin and linezolid compared to standard WHO treatment, alongside the use of aspirin versus placebo. It is a randomized controlled, phase III, multicenter trial conducted in sub-Saharan Africa, involving 768 participants aged 15 and older. The study will follow participants for 40 weeks and analyze outcomes using a Cox proportional hazard ratio model, adjusting for various factors such as HIV status and severity of TBM. Sub-studies will also explore pharmacokinetics and multi-omics in selected participants.

Why it matters

Who can join: the full rules

Inclusion criteria:

1. Age ≥ 15 years
2. TBM defined as "definite", "probable" or "possible"
3. 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.

Exclusion criteria:

* \> 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's running

• Treichville University Hospital
  Abidjan, Côte d’Ivoire Recruiting
• University Hospital Joseph Raseta Befelatanana
  Antananarivo, Madagascar Recruiting
• University Hospital Tambohobe
  Fianarantsoa, Madagascar Recruiting
• Kayelitsha District Hospital
  Cape Town, South Africa Recruiting
• Mitchells Plain Hospital
  Cape Town, South Africa Recruiting
• New Somerset Hospital
  Cape Town, South Africa Recruiting

Study contacts

• Principal investigator: Fabrice Bonnet, M.D., Ph.D. — University Hospital, Bordeaux
• Study coordinator: Fabrice Bonnet, M.D., Ph.D.
• Email: fabrice.bonnet@chu-bordeaux.fr
• Phone: +33 (0)5 56 79 58 26

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Tuberculous Meningitis in Indonesia: Characteristics, Treatments, Diagnostics, and Outcomes (2022–2025)

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  Recruiting at 5 sites Ina-Respond · Denpasar, Bali and 5 other locations · NCT07929519

• BPaLMZ for TB Meningitis: a two-stage trial comparing an experimental regimen to standard therapy

  This phase 2 trial tests whether the BPaLMZ combination can be better than standard TB meningitis treatment in adults living with HIV who have TB meningitis.

  Recruiting at 2 sites Phase 2 University of Minnesota · Kampala and 1 other locations · NCT07227779

• Using adalimumab to improve survival in HIV patients with tuberculosis meningitis

  This study is testing if adding a medication called adalimumab to the usual treatment can help HIV patients with tuberculosis meningitis live longer and stay safe.

  Recruiting Phase 2 ANRS, Emerging Infectious Diseases · Rio de Janeiro and 2 other locations · NCT05590455

• Six-month high-dose rifampicin and isoniazid with linezolid and pyrazinamide versus standard nine-month therapy for adult and adolescent tuberculous meningitis

  This study tests whether a six-month, high-dose antibiotic regimen (rifampicin, isoniazid, linezolid, and pyrazinamide) works better than the WHO nine-month treatment for adults and adolescents with tuberculous meningitis.

  Recruiting at 9 sites Phase 2 National Institute of Allergy and Infectious Diseases (NIAID) · Porto Alegre and 17 other locations · NCT05383742

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.