ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2023
Analysis of Dynamic Efficacy Endpoints of the Nix-TB Trial.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02333799 (A Phase 3 Open-label Trial Assessing the Safety and Efficacy of Bedaquiline Plus PA-824 Plus Linezolid in Participants With Pulmonary Infection of Either XDR-TB or Treatment Intolerant / Non-responsive MDR-TB.), which is not on this map. Cited by 13 papers, 2 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.
A Phase 3 Open-label Trial Assessing the Safety and Efficacy of Bedaquiline Plus PA-824 Plus Linezolid in Participants With Pulmonary Infection of Either XDR-TB or Treatment Intolerant / Non-responsive MDR-TB.
Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 16 citations in OpenAlex.
- Adverse events in bedaquiline- and pretomanid-based regimens for drug-resistant tuberculosis from trial, implementation and pharmacovigilance studies.British journal of clinical pharmacology · 2026Pooled it
- Updates on the Treatment of Drug-Susceptible and Drug-Resistant Tuberculosis: An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.American journal of respiratory and critical care medicine · 2025Guideline
- Applying a Pharmacometrics-Enabled Machine Learning Analysis to Predict 2-Month Culture Conversion Using Phase 2a Data in a Tuberculosis Clinical Trial.Clinical and translational science · 2026Trial
- A pharmacometric multistate model for predicting long-term treatment outcomes of patients with pulmonary TB.The Journal of antimicrobial chemotherapy · 2024Trial
- Pharmacokinetic-pharmacodynamic modeling of tuberculosis time to positivity and colony-forming unit to assess the response to dose-ranging linezolid.Antimicrobial agents and chemotherapy · 2024Trial
- Insights into the Role of Rifampicin Exposure and Clinical Baseline Covariates on the Response to Pulmonary Tuberculosis Treatment.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
- Current Status and Perspectives of Antibacterial Agents Belonging to 2-Oxazolidinones.Pharmaceuticals (Basel, Switzerland) · 2026Review
- A New Era in Tuberculosis Prevention and Treatment: Breakthroughs in Drug Development and Future Prospects.Infectious diseases and therapy · 2025Review
- Recent advancements in tuberculosis (TB) treatment regimens.Journal of family medicine and primary care · 2025Review
- Safety and Tolerability of Contezolid Versus Linezolid for Short-Term Treatment of Rifampicin-Resistant Pulmonary Tuberculosis: A Randomized Controlled Study.Infection and drug resistance · 2025Article
- Update in tuberculosis treatment: a scoping review of current practices.Breathe (Sheffield, England) · 2025Review
- Estimating Post-treatment Recurrence After Multidrug-Resistant Tuberculosis Treatment Among Patients With and Without Human Immunodeficiency Virus: The Impact of Assumptions About Death and Missing Follow-up.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Article
- The Safety and Efficacy of Prolonged Use of Bedaquiline for the Treatment of Patients with Pulmonary Multi-Drug Resistant/Rifampin-Resistant Tuberculosis: A Prospective, Cohort Study in China.Infection and drug resistance · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSafer, better, and shorter treatments for multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are an urgent global health need. The phase 3 clinical trial Nix-TB (NCT02333799) tested a 6-month treatment of MDR and XDR-TB consisting of high-dose linezolid, bedaquiline, and pretomanid (BPaL). In this study, we investigate the relationship between the pharmacokinetic characteristics of the drugs, patient characteristics and efficacy endpoints from Nix-TB.
methodsPharmacokinetic data were collected at weeks 2, 8, and 16. Efficacy endpoints including treatment outcomes, time to stable culture conversion, and longitudinal time to positivity in the mycobacterial growth indicator tube assay were each characterized using nonlinear mixed-effects modeling. Relationships between patient, treatment pharmacokinetics, and disease characteristics and efficacy endpoints were evaluated.
resultsData from 93 (85% of the total) participants were analyzed. Higher body mass index was associated with a lower incidence of unfavorable treatment outcomes. Median time to stable culture conversion was 3 months in patients with lower baseline burden compared with 4.5 months in patients with high baseline burden. Participants with minimal disease had steeper time to positivity trajectories compared with participants with high-risk phenotypes. No relationship between any drugs' pharmacokinetics (drug concentration or exposure metrics) and any efficacy outcomes was observed.
conclusionsWe have successfully described efficacy endpoints of a BPaL regimen from the Nix-TB trial. Participants with high-risk phenotypes significantly delayed time to culture conversion and bacterial clearance. The lack of a relationship between pharmacokinetic exposures and pharmacodynamic biomarkers opens the possibility to use lower, safer doses, particularly for toxicity-prone linezolid. CLINICAL TRIALS REGISTRATION: NCT02333799.
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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.