Trial reportThe New England journal of medicine2025
Trial of High-Dose Oral Rifampin in Adults with Tuberculous Meningitis.
Trial report in The New England journal of medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Adjunctive linezolid in patients with tuberculous meningitis for the prevention of mortality or neurologic disability: a meta-analysis of randomized controlled trials.BMC infectious diseases · 2026Pooled it
- High-dose rifampicin and clarithromycin for 4 weeks versus standard-dose rifampicin and clarithromycin for 8 weeks to treat Buruli ulcer: An open-label, individually randomized, controlled trial in Ghana.PLoS neglected tropical diseases · 2026Trial
- Immediate or high-dose antituberculosis therapy for HIV-related sepsis in Tanzania and Uganda (ATLAS): a phase 3, open-label, randomised, controlled, 2 × 2 factorial, superiority trial.The Lancet. Infectious diseases · 2026Trial
- Population Pharmacokinetic Modeling of Standard- and High-Dose Rifampicin for Tuberculosis Preventive Therapy in the 2R2 Randomized Controlled Trial.The Journal of infectious diseases · 2026Trial
- Beyond Rifampin: Evaluating Rifapentine and Rifabutin as Alternative Treatments for Tuberculous Meningitis.The Journal of infectious diseases · 2026Article
- Host-directed treatments for tuberculous meningitis utilizing a multi-platform approach across mouse and human models.Nature communications · 2026Article
- Cerebrospinal Fluid Concentrations of Bedaquiline, Pretomanid, and Linezolid During Curative Treatment of Fluoroquinolone-Resistant Pre-Extensively Drug-Resistant Tuberculous Meningitis.Open forum infectious diseases · 2026Article
- Cerebrospinal Fluid Hypo-inflammation Drives Mortality in HIV-Associated Tuberculous Meningitis.The Journal of infectious diseases · 2026Article
- Review
- Host-directed treatments for tuberculous meningitis: A multi-platform approach across mouse and human models.Research square · 2026Article
- A Year in Review on Tuberculosis and Non-tuberculous Mycobacteria Disease: A 2026 Update for Clinicians and Scientists.Pathogens & immunity · 2026Review
- Research overview-2025: integrating scientific progress to accelerate global tuberculosis elimination.Frontiers in tuberculosis · 2026Article
- Current and emerging therapies for pulmonary tuberculosis in adults.BMJ medicine · 2026Review
- Drug-induced liver injury as a strong independent predictor of in-hospital mortality in tuberculous meningitis: potential age-related effect modification suggested in a large lifespan cohort.Frontiers in medicine · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
36 authors.
Funding
Abstract
backgroundTuberculous meningitis is often lethal, and many survivors have disabilities despite antimicrobial treatment and adjunctive glucocorticoid therapy. Standard-dose rifampin has limited central nervous system penetration. Whether high-dose rifampin could improve survival outcomes is unknown.
methodsWe performed a double-blind, randomized, placebo-controlled clinical trial involving adults with tuberculous meningitis in Indonesia, South Africa, and Uganda. We assigned persons with and those without human immunodeficiency virus (HIV) coinfection to receive standard daily isoniazid, rifampin (at a dose of 10 mg per kilogram of body weight), ethambutol, and pyrazinamide plus either additional rifampin (for a cumulative dose of 35 mg per kilogram; high-dose group) or matched placebo (standard-dose group) for 8 weeks; participants in both groups received standard therapy for the remainder of the 9-to-12-month treatment course. The primary outcome was 6-month mortality.
resultsA total of 499 participants were included in the intention-to-treat population (249 randomly assigned to the high-dose group and 250 to the standard-dose group), of whom 304 (60.9%) were persons living with HIV and 428 (85.8%) had definite or probable tuberculous meningitis. During 6 months of follow-up, 109 participants (Kaplan-Meier estimate, 44.6%) in the high-dose group and 100 participants (Kaplan-Meier estimate, 40.7%) in the standard-dose group died (hazard ratio, 1.17; 95% confidence interval, 0.89 to 1.54; P = 0.25). Among the participants who died within 6 months, the median time to death was 13 days (interquartile range, 4 to 39) in the high-dose group and 24 days (interquartile range, 6 to 56) in the standard-dose group. Drug-induced liver injury occurred in 8.0% of the participants in the high-dose group and in 4.4% of those in the standard-dose group, but no deaths from drug-induced liver injury occurred.
conclusionsAmong persons with tuberculous meningitis, no evidence of beneficial effect from high-dose rifampin was observed, and the potential for a harmful effect cannot be ruled out. (Funded by the U.K. Medical Research Council and others; ISRCTN Registry number, ISRCTN15668391.).
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