Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 3INTERVENTIONAL

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

Q: Who can participate in NCT04145258?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

Q: How do I contact the trial site for NCT04145258?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Q: Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Q: Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

Intensified Tuberculosis Treatment to Reduce the Mortality of HIV-infected and Uninfected Patients With Tuberculosis Meningitis: a Phase III Randomized Controlled Trial (Acronym: INTENSE-TBM)

Intensified Tuberculosis Treatment to Reduce the Mortality of Patients With Tuberculous Meningitis (NCT04145258) is a Phase 3 interventional studying Tuberculous Meningitis, sponsored by Anrs, Emerging Infectious Diseases. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

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.

What Stage of Research Is This?

Phase 3 trials confirm efficacy and safety in large patient groups (often 300–3,000+) and form the evidence base for an FDA approval submission. For Tuberculous Meningitis, Phase 3 studies typically randomize participants between the investigational treatment and either a placebo or current standard of care. A successful Phase 3 result is the threshold most treatments need to clear before regulatory approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

A target enrollment of 768 participants makes this a sizable late-stage trial. Studies in this range typically have enough power to detect clinically meaningful differences from a comparator and to characterize less-common side effects.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Age ≥ 15 years 2. TBM defined as "definite", "probable" or "possible" 3. Signed willing to sign a consent form - 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. Who Should NOT Join This Trial: - \> 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). ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

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.

Treatments Being Tested

DRUG

Aspirin

Two tablets of aspirin 100 mg per day from inclusion (D-0) to end of Week-8 (W-8)

DRUG

Placebo of aspirin

Two placebo tablets with the same appearance of aspirin 100 mg per day from inclusion (D-0) to end of Week-8 (W-8)

DRUG

WHO TBM treatment

2 months of (R-H-Z-E) + 7 months of (R-H)

DRUG

Intensified TBM treatment

2 months of (HDR-L-H-Z-E) + 7 months of (R-H), with HDR=high-dose rifampicin and L=linezolid

Locations (13)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Cocody University Hospital

Abidjan, Côte d’Ivoire

Treichville University Hospital

Abidjan, Côte d’Ivoire

Yopougon University Hospital

Abidjan, Côte d’Ivoire

University Hospital Joseph Raseta Befelatanana

Antananarivo, Madagascar

University Hospital Tambohobe

Fianarantsoa, Madagascar

Morafeno University Hospital

Toamasina, Madagascar

Kayelitsha District Hospital

Cape Town, South Africa

Mitchells Plain Hospital

Cape Town, South Africa

New Somerset Hospital

Cape Town, South Africa

Dora Nginza Hospital

Port Elizabeth, South Africa

Livingstone and PE Central Hospitals

Port Elizabeth, South Africa

Mbarara Regional Reference Hospital

Mbarara, Uganda

Regional Reference Hospital of Kabale

Mbarara, Uganda

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT04145258), the sponsor (Anrs, Emerging Infectious Diseases), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT04145258 clinical trial studying?

Who can participate in NCT04145258?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT04145258?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT04145258. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT04145258. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.