Cardiac safety of bedaquiline, delamanid and moxifloxacin co-administered with or without varying doses of sutezolid or delpazolid for the treatment of drug-susceptible TB.
Abstract
Abstract Introduction Many drugs for the treatment of TB prolong the QTc interval, which is associated with an increased risk of developing a life-threatening arrhythmia known as torsades de pointes. Sutezolid and delpazolid are novel oxazolidinones with demonstrated bactericidal activity. We aimed to assess the effects of sutezolid or delpazolid co-administered with bedaquiline, delamanid and moxifloxacin on the QTcF interval (Fridericia’s correction). Furthermore, we developed a population pharmacodynamic model to assess the effects of drug exposure on the QTcTBT interval (TB-specific correction). Methods Participants were randomized to receive standard-dose bedaquiline, delamanid and moxifloxacin with varying doses of either sutezolid (no sutezolid, 600 mg daily, 1200 mg daily, 600 mg twice daily, 800 mg twice daily) or delpazolid (no delpazolid, 400 mg daily, 800 mg daily, 1200 mg daily, 800 mg twice daily). The QTc interval was determined using weekly ECG assessments. Results Data from 149 participants, yielding 2373 ECG observations were available for analysis. Nine participants (6.0%) experienced a Grade 3 QTcF prolongation as defined by the Common Terminology Criteria for Adverse Events v5.0. The population pharmacodynamic model predicted a 13.2 ms (95% CI: 10.9–15.3) increase of the QTcTBT in the first week of treatment, but no further increase after that. The exposure of bedaquiline’s M2 metabolite was found to drive part of the QTcTBT. No exposure–response…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 149 participants or records.
Read the paper
Related studies
- Synthesis, In Vitro and In Silico Molecular Docking Studies of Novel Phthalimide–Pyrimidine Hybrid Analogues to Thalidomide as Potent Antitubercular Agents
- Exploring the inhibitory performance of expired moxifloxacin and norfloxacin on copper corrosion in saline environment
- Molecular investigation of antimicrobial peptides against Helicobacter pylori proteins using a peptide-protein docking approach
- Screening of novel narrow-spectrum benzofuroxan derivatives for the treatment of multidrug-resistant tuberculosis through in silico, in vitro, and in vivo approaches
- Synthesis, Characterization, Anticancer, Antioxidant, and In Silico Evaluation of Semicarbazides and Thiosemicarbazides
- Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.