Trial reportEuropean journal of clinical pharmacology2013
NAT2 genotype guided regimen reduces isoniazid-induced liver injury and early treatment failure in the 6-month four-drug standard treatment of tuberculosis: a randomized controlled trial for pharmacogenetics-based therapy.
Trial report in European journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06585358 (DoseTB-individualised Dosing by Model-informed Precision Dosing for Pulmonary Tuberculosis), which is not on this map. Cited by 131 papers, 9 of them syntheses 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.
DoseTB-individualised Dosing by Model-informed Precision Dosing for Pulmonary Tuberculosis
Who cites it
131 citing papers in PubMed, 9 syntheses or guidelines pooled it, 269 citations in OpenAlex.
- Genetic polymorphisms and anti-tuberculosis drug-induced liver injury: an umbrella review of the evidence.International journal of clinical pharmacy · 2025Pooled it
- Efficacy, safety, and pharmacokinetics of isoniazid affected by NAT2 polymorphisms in patients with tuberculosis: A systematic review.Clinical and translational science · 2024Pooled it
- Effectiveness and Pharmacokinetic Exposures of First-Line Drugs Used to Treat Drug-Susceptible Tuberculosis in Children: A Systematic Review and Meta-Analysis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Pooled it
- Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.The European respiratory journal · 2023Pooled it
- 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
- Genetic testing for prevention of severe drug-induced skin rash.The Cochrane database of systematic reviews · 2019Pooled it
- The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2019Pooled it
- The association between the NAT2 genetic polymorphisms and risk of DILI during anti-TB treatment: a systematic review and meta-analysis.British journal of clinical pharmacology · 2018Pooled it
- Clinical Pharmacogenetic Testing and Application: Laboratory Medicine Clinical Practice Guidelines.Annals of laboratory medicine · 2017Guideline
- Impact of Pharmacogenetics on Pharmacokinetics of First-Line Antituberculosis Drugs in the HIRIF Trial.The Journal of infectious diseases · 2025Trial
- Effect of efavirenz-based antiretroviral therapy and high-dose rifampicin on the pharmacokinetics of isoniazid and acetyl-isoniazid.The Journal of antimicrobial chemotherapy · 2019Trial
- Evaluation of the Adequacy of WHO Revised Dosages of the First-Line Antituberculosis Drugs in Children with Tuberculosis Using Population Pharmacokinetic Modeling and Simulations.Antimicrobial agents and chemotherapy · 2018Trial
- Genetic Polymorphisms of Glutathione S-Transferase P1 (GSTP1) and the Incidence of Anti-Tuberculosis Drug-Induced Hepatotoxicity.PloS one · 2016Trial
- Association between human genomes and mycobacterial genomes contributes to severity and transmissibility of pulmonary tuberculosis.iScience · 2026Article
- HBV/HCV coinfection and anti-tuberculosis drug-induced liver injury: from risk assessment and exploration of mechanisms to preventive considerations.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Review
- Genetic Variants at the NAT2 and HLA-DOA are Associated With Anti-Tuberculosis Drug-Induced Liver Injury Susceptibility and Clinical Manifestations in Western Chinese Populations.Immunity, inflammation and disease · 2026Article
- Effect of kidney function on drug concentrations of first-line anti-tubercular treatment.Infection · 2026Article
- Acetylator status-guided rapid reintroduction of isoniazid in tuberculosis patients with drug-induced hepatotoxicity.Journal of clinical tuberculosis and other mycobacterial diseases · 2026Article
- Pharmacogenomics of antibacterial and antiviral therapies: Clinical actionability, evidence gaps, and future directions.Pharmacological reviews · 2026Review
- Pharmacokinetic and pharmacogenomic predictors of hepatotoxicity in the HIRIF trial for drug-susceptible tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
71 more citing papers are in PubMed but not listed here.
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 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThis study is a pharmacogenetic clinical trial designed to clarify whether the N-acetyltransferase 2 gene (NAT2) genotype-guided dosing of isoniazid improves the tolerability and efficacy of the 6-month four-drug standard regimen for newly diagnosed pulmonary tuberculosis.
methodsIn a multicenter, parallel, randomized, and controlled trial with a PROBE design, patients were assigned to either conventional standard treatment (STD-treatment: approx. 5 mg/kg of isoniazid for all) or NAT2 genotype-guided treatment (PGx-treatment: approx. 7.5 mg/kg for patients homozygous for NAT2 4: rapid acetylators; 5 mg/kg, patients heterozygous for NAT2 4: intermediate acetylators; 2.5 mg/kg, patients without NAT2 4: slow acetylators). The primary outcome included incidences of 1) isoniazid-related liver injury (INH-DILI) during the first 8 weeks of therapy, and 2) early treatment failure as indicated by a persistent positive culture or no improvement in chest radiographs at the 8th week.
resultsOne hundred and seventy-two Japanese patients (slow acetylators, 9.3 %; rapid acetylators, 53.5 %) were enrolled in this trial. In the intention-to-treat (ITT) analysis, INH-DILI occurred in 78 % of the slow acetylators in the STD-treatment, while none of the slow acetylators in the PGx-treatment experienced either INH-DILI or early treatment failure. Among the rapid acetylators, early treatment failure was observed with a significantly lower incidence rate in the PGx-treatment than in the STD-treatment (15.0 % vs. 38 %). Thus, the NAT2 genotype-guided regimen resulted in much lower incidences of unfavorable events, INH-DILI or early treatment failure, than the conventional standard regimen.
conclusionOur results clearly indicate a great potential of the NAT2 genotype-guided dosing stratification of isoniazid in chemotherapy for tuberculosis.
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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.