Efficacy and safety of a radiographic severity-stratified all-oral short treatment regimen for multidrug/rifampicin-resistant tuberculosis in China: an open-label, multicentre, randomised controlled, noninferiority trial

OBJECTIVES: This study evaluated the efficacy and safety of a radiographic severity-stratified, all-oral short-course treatment regimen (STR) for multidrug/rifampicin-resistant tuberculosis in China. METHODS: Enrolled participants were randomly divided (2:1) to receive either an all-oral STR or an 18-month regimen based on the 2019 WHO guidelines as the control. The STR group was divided into three subgroups according to radiographic severity scores. The primary efficacy endpoint was a favourable treatment outcome up to 6 months after discontinuation. The primary safety endpoint was grade ≥3 adverse events (AEs) during the study period. A prespecified noninferiority margin of <12 percentage points were used for the between-group difference in favourable outcomes. RESULTS: A total of 259 participants were randomly divided, with 173 and 86 assigned to the STR and control groups, respectively. In the modified intention-to-treat population, the favourable treatment outcome rate was 87.1% (148/170) in the STR group and 81.5% (66/81) in the control group. The between-group difference was 5.6 percentage points (95% CI, -5.7 to 13.8; p 0.03 for noninferiority). In the per-protocol population, the favourable treatment outcome rate was 89.0% (146/164) in the STR group and 83.1% (64/77) in the control group. The between-group difference was 5.9 percentage points (95% CI, -7.9 to 11.7; p 0.02 for noninferiority). Grade ≥3 AEs occurred significantly less often in the STR group than in the control group (27.7% vs. 43.0%, p < 0.01). CONCLUSIONS: The radiographic severity-stratified STR was noninferior to the traditional longer regimen in achieving favourable treatment outcomes and demonstrated better safety.