Trial reportAntimicrobial agents and chemotherapy2020
Drug Effect of Clofazimine on Persisters Explains an Unexpected Increase in Bacterial Load in Patients.
Trial report in Antimicrobial agents and chemotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- 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 loading dose of clofazimine to rapidly achieve steady-state-like concentrations in patients with nontuberculous mycobacterial disease.The Journal of antimicrobial chemotherapy · 2024Trial
- Therapeutic drug monitoring in tuberculosis.European journal of clinical pharmacology · 2024Review
- Clofazimine pharmacokinetics in HIV-infected adults with diarrhea: Implications of diarrheal disease on absorption of orally administered therapeutics.CPT: pharmacometrics & systems pharmacology · 2024Article
- Pharmacokinetics and cardiac safety of clofazimine in children with rifampicin-resistant tuberculosis.Antimicrobial agents and chemotherapy · 2024Observational
- New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians.Respiration; international review of thoracic diseases · 2023Review
- Combined quantitative tuberculosis biomarker model for time-to-positivity and colony forming unit to support tuberculosis drug development.Frontiers in pharmacology · 2023Article
- Standards for model-based early bactericidal activity analysis and sample size determination in tuberculosis drug development.Frontiers in pharmacology · 2023Article
- Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19.Microorganisms · 2022Article
- Pharmacokinetics and pharmacodynamics of anti-tuberculosis drugs: An evaluation ofFrontiers in pharmacology · 2022Review
- Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs.Clinical pharmacokinetics · 2021Review
- An optimized method for the detection and spatial distribution of aminoglycoside and vancomycin antibiotics in tissue sections by mass spectrometry imaging.Journal of mass spectrometry : JMS · 2021Article
- Quantification of Natural Growth of Two Strains of Mycobacterium Marinum for Translational Antituberculosis Drug Development.Clinical and translational science · 2020Article
- A model-based analysis identifies differences in phenotypic resistance between in vitro and in vivo: implications for translational medicine within tuberculosis.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- Difference in persistent tuberculosis bacteria between in vitro and sputum from patients: implications for translational predictions.Scientific reports · 2020Article
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 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antituberculosis (anti-TB) drug development is dependent on informative trials to secure the development of new antibiotics and combination regimens. Clofazimine (CLO) and pyrazinamide (PZA) are important components of recommended standard multidrug treatments of TB. Paradoxically, in a phase IIa trial aiming to define the early bactericidal activity (EBA) of CLO and PZA monotherapy over the first 14 days of treatment, no significant drug effect was demonstrated for the two drugs using traditional statistical analysis. Using a model-based analysis, we characterized the statistically significant exposure-response relationships for both drugs that could explain the original findings of an increase in the numbers of CFU with CLO treatment and no effect with PZA. Sensitive analyses are crucial for exploring drug effects in early clinical trials to make the right decisions for advancement to further development. We propose that this quantitative semimechanistic approach provides a rational framework for analyzing phase IIa EBA studies and can accelerate anti-TB drug development.
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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.