Evidence map›Paper›PMID 26760084›Full record

Trial reportThe New England journal of medicine2016

Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis.

A Dorothee Heemskerk, Nguyen D Bang, Nguyen T H Mai, Tran T H Chau, Nguyen H Phu, Pham P Loc, Nguyen V V Chau, Tran T Hien, Nguyen H Dung, Nguyen T N Lan and 14 more

2 registry-linked trialsAbstract readPragmatic Clinical TrialRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 154 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
154citing papers in PubMed, 11 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT03092817 phase3completednot on this mapstarted 2017, after this paper: background citation

A Randomized Double Blind Placebo Controlled Trial of Adjunctive Dexamethasone for the Treatment of HIV-infected Adults With Tuberculous Meningitis

TypeinterventionalSponsorOxford University Clinical Research Unit, VietnamRan2017 to 2023Enrolled520ConditionsTuberculosis, Tuberculous Meningitis, Drug-Induced Liver Injury, HIVArmsDexamethasone, Placebo
NCT03100786 phase3completednot on this mapstarted 2018, after this paper: background citation

A Randomized Double Blind Placebo Controlled Non-inferiority Trial of Adjunctive Dexamethasone for the Treatment of HIV-uninfected Adults With Tuberculous Meningitis Stratified by Leukotriene A4 Hydrolase Genotype

TypeinterventionalSponsorOxford University Clinical Research Unit, VietnamRan2018 to 2024Enrolled702ConditionsTuberculosis, Tuberculous Meningitis, Drug-Induced Liver InjuryArmsDexamethasone, Placebo
3 · Its place in the literature

Who cites it

154 citing papers in PubMed, 11 syntheses or guidelines pooled it.

  1. High dose of rifampicin in the treatment of tuberculous meningitis: a systematic review and meta-analysis of randomized controlled trials.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
    Pooled it
  2. A clinical practice guideline for tuberculous meningitis.The Lancet. Infectious diseases · 2026
    Guideline
  3. Safety of Triple-Dose Rifampin in Tuberculosis Treatment: A Systematic Review and Meta-Analysis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025
    Pooled it
  4. Pooled it
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  7. Model-Based Meta-analysis of Rifampicin Exposure and Mortality in Indonesian Tuberculous Meningitis Trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020
    Pooled it
  8. Pooled it
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  11. Corticosteroids for managing tuberculous meningitis.The Cochrane database of systematic reviews · 2016
    Pooled it
  12. Trial
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  17. Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
    Trial
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  20. Proresolving mediator profiles in cerebrospinal fluid are linked with disease severity and outcome in adults with tuberculous meningitis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Trial

94 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

A Dorothee HeemskerkFrom the Oxford University Clinical Research Unit (A.D.H., N.D.B., N.T.H.M., T.T.H.C., N.H.P., T.T.H., N.T.B.Y., D.T.M.H., J.N.D., L.M., T.T.V.T., M.W., G.E.T., J.J.F.), Pham Ngoc Thach Hospital for Tuberculosis and Lung Disease (N.D.B., N.H.D., N.T.N.L., N.H.L., N.N.L., L.T.P., N.N.V., N.Q.H., N.T.B.Y., D.T.M.H.), and Hospital for Tropical Diseases (N.H.P., P.P.L., N.V.V.C.) - all in Ho Chi Minh City, Vietnam; and the Nuffield Department of Medicine, University of Oxford, Oxford (A.D.H., J.N.D., L.M., M.W., G.E.T., J.J.F.), and Liverpool University, Liverpool (M.C.) - both in the United Kingdom.
Nguyen D Bang
Nguyen T H Mai
Tran T H Chau
Nguyen H Phu
Pham P Loc
Nguyen V V Chau
Tran T Hien
Nguyen H Dung
Nguyen T N Lan
Nguyen H Lan
Nguyen N Lan
Le T Phong
Nguyen N Vien
Nguyen Q Hien
Nguyen T B Yen
Dang T M Ha
Jeremy N Day
Maxine Caws
Laura Merson
Tran T V Thinh
Marcel Wolbers
Guy E Thwaites
Jeremy J Farrar

Funding

Medical Research Council G1100684Wellcome Trust
6 · The paper itself

Abstract

backgroundTuberculous meningitis is often lethal. Early antituberculosis treatment and adjunctive treatment with glucocorticoids improve survival, but nearly one third of patients with the condition still die. We hypothesized that intensified antituberculosis treatment would enhance the killing of intracerebral Mycobacterium tuberculosis organisms and decrease the rate of death among patients.

methodsWe performed a randomized, double-blind, placebo-controlled trial involving human immunodeficiency virus (HIV)-infected adults and HIV-uninfected adults with a clinical diagnosis of tuberculous meningitis who were admitted to one of two Vietnamese hospitals. We compared a standard, 9-month antituberculosis regimen (which included 10 mg of rifampin per kilogram of body weight per day) with an intensified regimen that included higher-dose rifampin (15 mg per kilogram per day) and levofloxacin (20 mg per kilogram per day) for the first 8 weeks of treatment. The primary outcome was death by 9 months after randomization.

resultsA total of 817 patients (349 of whom were HIV-infected) were enrolled; 409 were randomly assigned to receive the standard regimen, and 408 were assigned to receive intensified treatment. During the 9 months of follow-up, 113 patients in the intensified-treatment group and 114 patients in the standard-treatment group died (hazard ratio, 0.94; 95% confidence interval, 0.73 to 1.22; P=0.66). There was no evidence of a significant differential effect of intensified treatment in the overall population or in any of the subgroups, with the possible exception of patients infected with isoniazid-resistant M. tuberculosis. There were also no significant differences in secondary outcomes between the treatment groups. The overall number of adverse events leading to treatment interruption did not differ significantly between the treatment groups (64 events in the standard-treatment group and 95 events in the intensified-treatment group, P=0.08).

conclusionsIntensified antituberculosis treatment was not associated with a higher rate of survival among patients with tuberculous meningitis than standard treatment. (Funded by the Wellcome Trust and the Li Ka Shing Foundation; Current Controlled Trials number, ISRCTN61649292.).

Indexed as

AdultAIDS-Related Opportunistic InfectionsAntitubercular AgentsDouble-Blind MethodDrug Resistance, BacterialDrug Therapy, CombinationFemaleHIV InfectionsHumansKaplan-Meier EstimateLevofloxacinMaleMiddle AgedMycobacterium tuberculosisProportional Hazards ModelsRifampinAntitubercular AgentsLevofloxacinRifampin

Identifiers

PMID26760084

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.