A PHASE 3, multinational trial has shown that several new 9-month, all-oral regimens for fluoroquinolone-susceptible, rifampin-resistant tuberculosis (TB) are as effective as the standard longer-duration therapy, offering a promising alternative for patients.
The study was an open-label, randomised, controlled noninferiority trial evaluating five novel treatment regimens containing bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx), moxifloxacin (M), clofazimine (C), and pyrazinamide (Z). Participants were randomly assigned to one of these regimens or the standard treatment, with allocation determined through Bayesian response-adaptive randomisation. The primary endpoint was a favourable outcome at Week 73, defined by sustained negative sputum cultures or positive clinical and radiological progression. The study set a noninferiority margin of -12 percentage points.
Among 754 participants randomised, 699 were included in the modified intention-to-treat analysis. Of those receiving standard therapy, 80.7% achieved a favourable outcome. Four of the novel regimens (BCLLfxZ, BLMZ, BDLLfxZ, and DCMZ) were deemed noninferior, with risk differences from standard therapy of 9.8 percentage points (95% CI: 0.9–18.7), 8.3 percentage points (95% CI: -0.8–17.4), 4.6 percentage points (95% CI: -4.9–14.1), and 2.5 percentage points (95% CI: -7.5–12.5), respectively. The DCMZ regimen, however, did not maintain noninferiority in the per-protocol population. Safety profiles were comparable across all regimens, with Grade 3 or higher adverse events occurring at similar rates. Hepatotoxicity of Grade 3 or higher was reported in 11.7% of participants overall, compared to 7.1% in the standard-therapy group.
These findings suggest that shorter, all-oral regimens could offer an effective and safer alternative for rifampin-resistant TB treatment, potentially improving global treatment accessibility and adherence.
Ada Enesco, EMJ
Reference
Guglielmetti L et al.; endTB Clinical Trial Team. Oral regimens for rifampin-resistant, fluoroquinolone-susceptible tuberculosis. N Engl J Med. 2025;392(5):468-482.
