Treatment Shortening of Drug-Sensitive Pulmonary Tuberculosis Using High Dose Rifampicin to 3 Months After Culture Conversion (Hi-DoRi-3): A Phase 3, Multicenter, Randomized, Open-label, Clinical Trial

In this multicenter, randomized, open-label, phase III clinical trial, we could not conclude that the regimen including high-dose rifampin over an individualized duration (12 weeks after sputum culture conversion) was non-inferior to the standard 6-month regimen for drug-susceptible tuberculosis patients. In the mITT (Modified Intention-To-Treat) analysis, which is the primary analysis population of this clinical trial, there were 10 cases (31.25%) with unfavorable outcomes in the control group and 10 cases (38.46%) in the investigational group 18 months after treatment, with a difference of 7.21% (95% CI, 8 to 31.86) between the two groups. This did not meet the pre-defined non-inferiority margin of 6%. The treatment success rate at the end of treatment was 92.31% in the test group, which was about 4.81% higher than the control group's 87.50%, but this difference was not statistically significant. There were no statistically significant differences between the two groups in the time to unfavorable treatment outcome or the time to culture conversion in liquid media. In comparing the time to relapse after treatment completion, only one case of relapse was confirmed in the test group, but there was no statistically significant difference between the two groups. During the treatment period, 89.29% of the investigational group and 92.11% of the control group experienced adverse events, with 36% in the investigational group and 31.43% in the control group experiencing drug-related adverse events. Among these, two serious adverse events were reported only in the control group. In conclusion, while the high-dose rifampin regimen may have a shorter treatment duration compared to the standard treatment, the non-inferiority of the regimen including high-dose rifampin in terms of treatment efficacy was not demonstrated, and no statistically significant differences were found in other indicators between the two groups. Although we initially planned to recruit 926 participants, only 76 were enrolled due to COVID-19, which is only 8.2% of the recruitment target, making the sample size statistically insufficient. Therefore, there are limitations to the validity and generalizability of the results.