Six-Month Regimen Effective for Rifampicin-Resistant Tuberculosis: NEJM

The investigators constructed a pragmatic, open-label design trial under the challenging, very endemic, clinical context of South Africa. The researchers selected participants above the age of six presenting with rifampicin-resistant tuberculosis involving the lungs. This trial differed significantly from previous trials due to its inclusivity towards at-risk groups like participants who are pregnant or lactating and people with existing fluoroquinolone-resistant tuberculosis, making sure that the results could be applied in practice. Patients were randomly assigned at a ratio of one to one to either six-month trial strategy or nine-month standard of care strategy used in South African public health system.

The experimental strategy involved an intensive all-oral strategy of bedaquiline, linezolid, delamanid, and levofloxacin, clofazimine, or both for six months. Importantly, the clinicians modified the doses of certain drugs and dosage according to the second-line drug susceptibility testing. The primary effectiveness measure is defined by a completely successful clinical outcome, which is cure or completion of treatment, measured at the end of the treatment period and after seventy-six weeks from initial randomization.

Key findings:

• The final stage of statistical analysis on the clinical trial registry led to conclusive numbers that conclusively showed that the short protocol was a proven and safe alternative to the existing conventional treatment protocols.
• Of the total of 432 individuals that were screened by the medical professionals, 403 patients were finally confirmed to meet the criteria and underwent randomization.
• This patient pool was evenly divided, with 203 being part of the short protocol group and 200 forming the control group using the traditional standard of care.
• In the final seventy-six-week evaluation period, the successful outcome of the intervention was achieved for 174 out of 202 patients in the trial strategy group with a success rate of 86.1 percent.
• This equated to the control group that had a success rate of 86.0 percent among 172 out of 200 patients.
• For the risk difference in the two main groups, the calculated adjusted risk difference was only -0.2 percentage points with a narrow 95% confidence interval that ranged between -6.9 and 6.5 percentage points.
• This gave a definite non-inferiority value of P = 0.001, well below the predefined ten percentage point non-inferiority margin.
• In terms of safety, there were 63 serious adverse events of grade 3 or above for 202 patients in the short course arm, constituting 31.2%, compared to 74 out of 200 patients in the control arm, constituting 37.0%, while exactly 10 patients died in both arms due to advanced disease progression.

In summary, regarding a successful outcome in patients of South Africa who suffered from rifampicin-resistant tuberculosis, the trial treatment strategy was not inferior to the standard of care strategy. There were no differences in the safety of both treatment strategies. Definitive results of phase 3 randomized clinical trials serve as an essential empirical basis for pulmonology, demonstrating the capability of short-term oral strategies to control highly resistant pathogens.

Reference:

Conradie, F., Badat, T., Poswa, A., Rajaram, S., Kooverjee, S., Maartens, G., Meintjes, G., Hughes, J., Schaaf, H. S., Howell, P., Ndjeka, N., & Phillips, P. P. J. (2026). A Pragmatic Trial of a 6-Month Strategy for Rifampicin-Resistant Tuberculosis. New England Journal of Medicine, 394(24), 2429–2439. https://doi.org/10.1056/nejmoa2503687