Shortened BDLC Regimen Not Noninferior for Drug-Resistant TB

TUESDAY, July 22, 2025 (HealthDay News) — For preextensively drug resistant tuberculosis (TB), a shortened bedaquiline, delamanid, linezolid, and clofazimine (BDLC) regimen is not noninferior to longer standard of care, according to a study published online July 16 in The Lancet Respiratory Medicine.

Lorenzo Guglielmetti, M.D., Ph.D., from Médecins Sans Frontières in Paris, and colleagues conducted an open-label, noninferiority, randomized phase 3 trial in 10 hospitals involving participants aged 15 years or older who had pulmonary TB with resistance to rifampicin and fluoroquinolones. Participants were randomly assigned to receive BDLC or individualized World Health Organization-recommended longer standard of care (control) in a 2:1 ratio (219 and 105 individuals, respectively). BDLC was administered for nine months for extensive disease and for six months for limited disease.

The researchers found that at week 73, favorable outcome was reached by 87 and 89 percent of the modified intention-to-treat population in the BDLC and control groups, respectively (adjusted risk difference, 0.2 percent; P_{noninferiority} = 0.0051) and by 88 and 93 percent of the per-protocol population (adjusted risk difference, −3.5 percent; P_{noninferiority} = 0.037). Overall noninferiority was not demonstrated. At least one grade 3 or higher adverse event occurred in 68 and 73 percent of participants in the BDLC and control groups, respectively, with eight and two all-cause deaths occurring by week 73 (4 and 2 percent, respectively).

“This shorter regimen is not a surefire cure for everyone,” co-senior author Carole D. Mitnick, Sc.D., from Brigham and Women”s Hospital and Harvard Medical School in Boston, said in a statement. “The big takeaway is that we might need a more tailored approach to treatment of this kind of resistant TB.”

One author disclosed ties to Janssen Pharmaceuticals.

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