Six-month drug combo matches longer treatment for drug-resistant TB

Rifampicin-resistant tuberculosis (RR-TB) is a form of TB that does not respond to one of the key antibiotics used to treat the disease, and safer, more effective regimens are urgently needed. Francesca Conradie and colleagues tested a new, shorter approach to treating RR-TB in a clinical trial in South Africa. The study was a phase III, open-label, multi-centre, pragmatic, noninferiority randomised-controlled strategy trial, designed to see whether a six-month treatment strategy could match the outcomes of the then-current South African nine-month or longer regimen. The trial enrolled people aged six years and older, including pregnant and breastfeeding women and people with fluoroquinolone resistance, and randomly assigned them to either the new six-month strategy or the standard longer regimen. The six-month Study Strategy combined bedaquiline, delamanid, linezolid, levofloxacin and/or clofazimine (BDLLfxC). Treatment for both groups was adjusted based on the second-line drug susceptibility test results. The main measure of success was completing treatment and having a successful outcome at the end of a 76-week follow-up period, tested against a 10% non-inferiority margin (trial registration NCT04062201).

The trial screened 432 people and randomised 403 participants into two groups, with 203 assigned to the control strategy and 200 to the study strategy. One participant in the study strategy arm never started treatment. Outcomes were very similar between groups. The abstract reports successful outcomes in 172/200 (86.0%) in the control strategy and 174/202 (86.1%) in the study strategy; the adjusted risk difference was -0.2% with a 95% confidence interval of -6.9% to 6.5%, which met the prespecified test for non-inferiority (p=0.0014). Serious health events during treatment occurred in both arms: 74 participants (37.0%) in the control strategy and 63 participants (31.2%) in the study strategy experienced severe adverse events while on treatment. Ten participants died in each strategy. These results show that the BDLLfxC six-month approach produced similar success and a comparable safety profile to the standard longer South African regimen when evaluated with the trial's predefined measures.

The trial’s conclusion, reported by Francesca Conradie and the research team, is clear: the six-month BDLLfxC study strategy demonstrated non-inferior effectiveness and safety comparable to the South African standard-of-care TB regimen. Because the trial included a broad group of participants — people aged six and older, pregnant and breastfeeding women, and people with fluoroquinolone resistance — the findings are relevant to many patients who face RR-TB. The pragmatic design strengthens the case that the results may reflect what happens in routine care settings. If health authorities accept these findings, this shorter regimen could offer an alternative to nine-month or longer treatments without losing effectiveness or adding measurable safety risk, based on the trial’s endpoints. The study provides data that policymakers, clinicians and patients can use in discussions about updating RR-TB treatment options.