Delamanid-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China: focus on the safety

Multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) continues to pose a substantial global public health threat. Delamanid, a nitroimidazo-oxazole derivative, has demonstrated therapeutic benefit in controlled clinical trials; however, large-scale real-world safety data remain limited, particularly among Chinese patients. This study aimed to evaluate the safety of delamanid administered alongside optimized background regimens (OBRs) in a real-world cohort of Chinese patients with MDR/RR-TB and to provide additional evidence to inform clinical safety monitoring. A prospective, multicenter observational study was conducted at 26 hospitals across China from July 2020 to August 2023. A total of 608 patients with microbiologically confirmed MDR/RR-TB, pre-extensively drug-resistant tuberculosis (pre-XDR-TB), or extensively drug-resistant tuberculosis (XDR-TB) who received delamanid plus OBRs were enrolled. Safety evaluations encompassed adverse events (AEs), serious adverse events (SAEs), adverse drug reactions (ADRs), and targeted monitoring of the QT interval corrected using Fridericia’s formula (QTcF). All data were captured using a standardized electronic data management system and analyzed with SAS 9.4. Of the 608 participants, 352 (57.9%) reported AEs, and 331 (54.4%) experienced ADRs. SAEs were documented in 39 (6.4%) patients. The most frequently reported AEs by system organ class were blood and lymphatic system disorders (24.5%), investigations (22.7%; mainly ECG QT prolongation), and hepatobiliary disorders (15.6%). Delamanid-related ADRs occurred in 167 (27.5%) patients, most commonly QT prolongation (17.1%), gastrointestinal disturbances (3.3%), and hepatotoxicity (3.1%). QTcF prolongation, defined as an increase ≥ 60 ms from baseline or an absolute value ≥ 500 ms, was observed in 138 (22.7%) individuals. Multivariable logistic regression identified age as the only significant factor associated with QTcF prolongation: compared with patients aged < 25 years, those aged 25–44 years (adjusted odds ratio [aOR] = 0.232, 95% confidence interval [CI]: 0.150–0.361) and ≥ 45 years (aOR = 0.386, 95% CI: 0.243–0.614) had significantly lower odds of developing QTcF prolongation. No previously unrecognized safety concerns were observed during the avaliable follow-up. In this large real-world cohort from China, the observed safety profile of delamanid combined with OBRs was generally consistent with previously established characteristics, with no new safety signals identified. Although careful monitoring of QT interval changes remains essential, the observed tolerability provides supportive real-world safety evidence regarding the use of delamanid-containing regimens in patients with MDR/RR-TB. The study was registered at clinicaltrials.gov (identifier NCT04421495) on June 9, 2020.