Tuberc Respir Dis.  2025 Jan;88(1):170-180. 10.4046/trd.2024.0099.

High-Dose Rifampicin for 3 Months after Culture Conversion for Drug-Susceptible Pulmonary Tuberculosis

• Kwak N
• Kim JY
• Kim HJ
• Kwon BS
• Lee JH
• Mok J
• Kwon YS
• Kang YA
• Park Y
• Lee JY
• Jeon D
• Lee JK
• Yang JS
• Whang J
• Kim KJ
• Kim YR
• Cheon M
• Park J
• Hahn S
• Yim JJ

• KMID: 2562639
• DOI: http://doi.org/10.4046/trd.2024.0099

Abstract

Background
This study aimed to determine whether a shorter high-dose rifampicin regimen is non-inferior to the standard 6-month tuberculosis regimen.
Methods
This multicenter, randomized, open-label, non-inferiority trial enrolled participants with respiratory specimen positivity by Xpert MTB/RIF assay or Mycobacterium tuberculosis culture without rifampicin-resistance. Participants were randomized at 1:1 to the investigational or control group. The investigational group received high-dose rifampicin (30 mg/kg/day), isoniazid, and pyrazinamide until culture conversion, followed by high-dose rifampicin and isoniazid for 12 weeks. The control group received the standard 6-month regimen. The primary outcome was the rate of unfavorable outcomes at 18 months post-randomization. The non-inferiority margin was set at <6% difference in unfavorable outcomes rates. The study is registered with ClinicalTrials.gov (NCT04485156)
Results
Between 4 November 2020 and 3 January 2022, 76 participants were enrolled. Of these, 58 were included in the modified intention-to-treat analysis. Unfavorable outcomes occurred in 10 (31.3%) of 32 in the control group and 10 (38.5%) of 26 in the investigational group. The difference was 7.2% (95% confidence interval, ∞ to 31.9%), failing to prove non-inferiority. Serious adverse events and grade 3 or higher adverse events did not differ between the groups.
Conclusion
The shorter high-dose rifampicin regimen failed to demonstrate non-inferiority but had an acceptable safety profile.

Keyword

High-Dose Rifampicin; Tuberculosis; Treatment Shortening