Trial reportClinical pharmacology and therapeutics2020
Pharmacokinetics and Pharmacodynamics of Intensive Antituberculosis Treatment of Tuberculous Meningitis.
Trial report in Clinical pharmacology and therapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05124678 (A Phase II Trial to Describe the Pharmacokinetics, Safety and Efficacy of Pharmacogenetics-guided Dosing of Isoniazid in Patients With HIV-associated TB), which is not on this map. Cited by 25 papers, 4 of them syntheses that pooled 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.
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.
A Phase II Trial to Describe the Pharmacokinetics, Safety and Efficacy of Pharmacogenetics-guided Dosing of Isoniazid in Patients With HIV-associated TB
Who cites it
25 citing papers in PubMed, 4 syntheses or guidelines pooled it, 40 citations in OpenAlex.
- 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 · 2026Pooled it
- A clinical practice guideline for tuberculous meningitis.The Lancet. Infectious diseases · 2026Guideline
- Influence of N-acetyltransferase 2 (NAT2) genotype/single nucleotide polymorphisms on clearance of isoniazid in tuberculosis patients: a systematic review of population pharmacokinetic models.European journal of clinical pharmacology · 2022Pooled it
- Intensified Antituberculosis Therapy Regimen Containing Higher Dose Rifampin for Tuberculous Meningitis: A Systematic Review and Meta-Analysis.Frontiers in medicine · 2022Pooled it
- Population pharmacokinetics of pyrazinamide and isoniazid in plasma and cerebrospinal fluid from South African adults with tuberculous meningitis.Antimicrobial agents and chemotherapy · 2025Trial
- Plasma Pharmacokinetics of High-Dose Oral versus Intravenous Rifampicin in Patients with Tuberculous Meningitis: a Randomized Controlled Trial.Antimicrobial agents and chemotherapy · 2021Trial
- Central nervous system antituberculosis drug exposures in a rabbit model of tuberculous meningitis.Antimicrobial agents and chemotherapy · 2026Article
- Article
- Development and validation of a liquid chromatography-tandem mass spectrometry assay for the simultaneous analysis of isoniazid and pyrazinamide in cerebrospinal fluid.Journal of pharmaceutical and biomedical analysis · 2025Article
- Article
- Efficacy and safety of higher dose rifampicin in adults with presumed drug-susceptible tuberculosis: an updated systematic review and meta-analysis.EClinicalMedicine · 2024Article
- Extracorporeal membrane oxygenation in acute respiratory distress syndrome caused by elderly tuberculous meningitis: a case report and review of the literature.Frontiers in medicine · 2024Article
- Tuberculous meningitis diagnosis and treatment: classic approaches and high-throughput pathways.Frontiers in immunology · 2024Review
- Advancing Diagnosis and Treatment in People Living with HIV and Tuberculosis Meningitis.Current HIV/AIDS reports · 2023Review
- Physiologically-Based Pharmacokinetic Modelling to Predict the Pharmacokinetics and Pharmacodynamics of Linezolid in Adults and Children with Tuberculous Meningitis.Antibiotics (Basel, Switzerland) · 2023Article
- Population Pharmacokinetic Modeling and Probability of Target Attainment of Ceftaroline in Brain and Soft Tissues.Antimicrobial agents and chemotherapy · 2022Article
- Tissue Penetration of Antimicrobials in Intensive Care Unit Patients: A Systematic Review-Part II.Antibiotics (Basel, Switzerland) · 2022Review
- Optimizing Dosing and Fixed-Dose Combinations of Rifampicin, Isoniazid, and Pyrazinamide in Pediatric Patients With Tuberculosis: A Prospective Population Pharmacokinetic Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Intrathecal therapy for tuberculous meningitis: propensity-matched cohort study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2022Article
- Whether Patients With Stage Ⅱ/Ⅲ Colorectal Cancer Benefit From Adjuvant Chemotherapy: A Modeling Analysis of Literature Aggregate Data.Frontiers in pharmacology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
The most effective antituberculosis drug treatment regimen for tuberculous meningitis is uncertain. We conducted a randomized controlled trial comparing standard treatment with a regimen intensified by rifampin 15 mg/kg and levofloxacin for the first 60 days. The intensified regimen did not improve survival or any other outcome. We therefore conducted a nested pharmacokinetic/pharmacodynamic study in 237 trial participants to define exposure-response relationships that might explain the trial results and improve future therapy. Rifampin 15 mg/kg increased plasma and cerebrospinal fluid (CSF) exposures compared with 10 mg/kg: day 14 exposure increased from 48.2 hour·mg/L (range 18.2-93.8) to 82.5 hour·mg/L (range 8.7-161.0) in plasma and from 3.5 hour·mg/L (range 1.2-9.6) to 6.0 hour·mg/L (range 0.7-15.1) in CSF. However, there was no relationship between rifampin exposure and survival. In contrast, we found that isoniazid exposure was associated with survival, with low exposure predictive of death, and was linked to a fast metabolizer phenotype. Higher doses of isoniazid should be investigated, especially in fast metabolizers.
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What OpenQuestion holds
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.