All-Oral Strategy for Rifampicin-Resistant TB Tested in South Africa
Key Takeaways
- Successful outcomes were observed in 86.1% and 86.0% of the two groups, and the shorter strategy met the prespecified noninferiority criterion.
- Grade 3 or higher adverse events occurred in 31.2% and 37.0% during treatment, and 10 participants in each group died.
The phase 3, open-label, pragmatic, randomized, controlled noninferiority trial was conducted in South Africa. Participants were 6 years of age or older and had pulmonary rifampicin-resistant tuberculosis, including pregnant or breastfeeding persons and those with fluoroquinolone-resistant disease. Among 432 screened persons, 403 underwent randomization, with 203 assigned to the 6-month strategy and 200 to the 9-month standard-of-care regimen. The trial strategy used bedaquiline, linezolid, delamanid, and levofloxacin or clofazimine or both for 6 months, all given orally.
The primary efficacy end point was successful outcome, defined as cure or completion of treatment at the end of therapy and 76 weeks after randomization. The noninferiority margin was 10 percentage points for the comparison with the standard-of-care regimen. Successful outcome occurred in 174 of 202 participants in the trial-strategy group and 172 of 200 in the control group. These findings corresponded to 86.1% and 86.0%, with an adjusted risk difference of -0.2 percentage points and a 95% confidence interval of -6.9 to 6.5. The noninferiority analysis yielded P=0.001, and the shorter strategy was noninferior on the primary efficacy measure.
The primary safety end point was an adverse event of grade 3 or higher during treatment. Such events occurred in 63 of 202 participants, or 31.2%, in the trial-strategy group. In the control group, 74 of 200 participants, or 37.0%, had grade 3 or higher adverse events during treatment. Ten participants in each group died during the study.