Delamanid Proves Safe in Large Real-World Study of Drug-Resistant Tuberculosis in China

One of the largest real-world safety assessments of delamanid, a key drug in the fight against multidrug-resistant tuberculosis, has delivered reassuring news from China. A prospective, multicenter observational study spanning 26 hospitals and 608 patients has found that the safety profile of delamanid-containing regimens in routine clinical practice closely mirrors what was established in controlled clinical trials, with no previously unrecognized safety signals emerging during follow-up. The findings, published in BMC Infectious Diseases, offer clinicians and public health authorities valuable evidence that this critical medicine can be deployed widely without unexpected hazards.

Multidrug-resistant and rifampicin-resistant tuberculosis, collectively known as MDR/RR-TB, remains one of the most formidable challenges in global infectious disease control. When the bacteria that cause tuberculosis become resistant to isoniazid and rifampicin, the two most powerful first-line antibiotics, treatment options narrow dramatically and the regimens that remain are longer, more toxic, and less effective. For patients whose disease progresses to pre-extensively or extensively drug-resistant tuberculosis, the therapeutic arsenal shrinks even further, making every usable drug precious.

Delamanid, a nitroimidazo-oxazole derivative, was developed specifically to address this gap. The drug works through a mechanism distinct from most classical anti-tuberculosis agents: it blocks the synthesis of mycolic acids, essential components of the mycobacterial cell wall, thereby killing the bacillus while interfering with its energy metabolism. Controlled clinical trials demonstrated its therapeutic benefit, and it has since become a cornerstone of optimized background regimens, the individually tailored combinations of drugs assembled around core agents for each resistant case. Yet despite its growing importance, large-scale real-world safety data have remained limited, particularly for Chinese patients, who represent a substantial share of the global burden of drug-resistant tuberculosis.

To close this evidence gap, researchers led by teams at Beijing Chest Hospital, Capital Medical University, conducted a prospective observational study at 26 hospitals across China between July 2020 and August 2023. They enrolled 608 patients with microbiologically confirmed MDR/RR-TB, pre-XDR-TB, or XDR-TB, all of whom received delamanid alongside optimized background regimens. The study was registered at clinicaltrials.gov under identifier NCT04421495 on June 9, 2020, and was conducted in accordance with the Declaration of Helsinki, with ethics approval from the leading center and written informed consent from all participants.

The safety evaluation was comprehensive, encompassing adverse events, serious adverse events, and adverse drug reactions, together with targeted cardiac monitoring. Because delamanid is known to prolong the QT interval, the portion of the electrocardiographic cycle representing ventricular repolarization, the investigators systematically measured the QT interval corrected using Fridericia’s formula, abbreviated QTcF. Prolongation of this interval matters because extreme QT stretching can predispose patients to torsades de pointes, a potentially life-threatening arrhythmia. All data were captured through a standardized electronic data management system and analyzed with SAS 9.4, ensuring consistency across the many participating centers.

The headline numbers paint a picture of tolerability broadly consistent with prior knowledge. Among the 608 participants, 352 patients, or 57.9 percent, reported at least one adverse event, while 331 patients, or 54.4 percent, experienced adverse drug reactions. Serious adverse events were documented in 39 patients, representing 6.4 percent of the cohort. When adverse events were grouped by system organ class, the most frequently affected categories were blood and lymphatic system disorders at 24.5 percent, investigations at 22.7 percent, driven mainly by electrocardiographic QT prolongation, and hepatobiliary disorders at 15.6 percent. These patterns reflect the cumulative toxicity of multidrug regimens rather than delamanid alone, since patients typically take five or more medications for many months.

Drilling down to reactions specifically attributed to delamanid, the investigators found that 167 patients, or 27.5 percent, experienced at least one. The most common was QT prolongation, affecting 17.1 percent of the cohort, followed by gastrointestinal disturbances at 3.3 percent and hepatotoxicity at 3.1 percent. QTcF prolongation, defined either as an increase of at least 60 milliseconds from baseline or as an absolute value of at least 500 milliseconds, was observed in 138 individuals, or 22.7 percent of participants. This rate falls within the range documented in earlier trials, reinforcing the message that cardiac monitoring, rather than avoidance of the drug, is the appropriate clinical response.

Perhaps the most intriguing analytical finding concerned who develops QT prolongation. Using multivariable logistic regression, the researchers identified age as the only significant factor associated with QTcF prolongation, and the direction of the effect ran counter to many clinicians’ intuitions. Compared with patients younger than 25 years, those aged 25 to 44 years had significantly lower odds of developing QTcF prolongation, with an adjusted odds ratio of 0.232 and a 95 percent confidence interval of 0.150 to 0.361. Patients aged 45 years or older also had lower odds, with an adjusted odds ratio of 0.386 and a 95 percent confidence interval of 0.243 to 0.614. In other words, the youngest patients in the cohort were the most likely to experience electrocardiographic changes, a pattern that suggests heightened vigilance and more frequent ECG surveillance may be warranted for adolescents and young adults receiving delamanid.

The study’s scale and design give its conclusions considerable weight. By enrolling more than 600 patients across 26 hospitals in a routine care setting, the investigators captured a far broader spectrum of patients than typical randomized trials do, including individuals with comorbidities, varying disease severity, and diverse background regimens that would often exclude trial participants. The prospective structure and standardized electronic data capture minimized the reporting inconsistencies that plague retrospective pharmacovigilance studies. The result is one of the clearest real-world portraits to date of how delamanid behaves outside the controlled environment of a clinical trial.

For global tuberculosis programs, the implications are practical and timely. The World Health Organization has encouraged the adoption of shorter, all-oral regimens for drug-resistant tuberculosis, and combinations that include both delamanid and bedaquiline, another QT-prolonging agent, are increasingly used despite theoretical concerns about additive cardiac effects. The Chinese cohort’s finding that no new safety signals emerged during available follow-up supports the continued expansion of delamanid-containing therapy, provided that the established monitoring framework, periodic electrocardiography and serum potassium assessment, is maintained. The authors conclude that the observed tolerability provides supportive real-world safety evidence for delamanid use in patients with MDR/RR-TB, while emphasizing that careful QT interval monitoring remains essential. As drug-resistant tuberculosis continues to pose a substantial public health threat, evidence of this kind, generated in the clinics where patients are actually treated, is what ultimately transforms a promising experimental drug into a dependable public health tool.

Subject of Research: Real-world safety of delamanid-containing regimens in patients with multidrug-resistant tuberculosis in China

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

Article References: Zhu, Y.-Q., Gao, M.-Q., Du, J., Liang, R.-X., Wu, G.-H., Pei, Y., Yan, X.-F., Cai, Q.-S., Huang, Y.-P., Huang, Z.-F., Wu, Y.-Q., Li, X.-J., Liu, Q.-Q., Jin, L., Wu, Q.-H., Xiong, Y., Li, M.-W., Wang, J.-Y., Kuang, H.-B., … Gao, J.-T. (2026). Delamanid-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China: focus on the safety. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14540-8

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14540-8

Keywords: delamanid, multidrug-resistant tuberculosis, MDR/RR-TB, QT prolongation, drug safety, tuberculosis treatment, China, adverse drug reactions, pharmacovigilance, XDR-TB, optimized background regimens, cardiac monitoring