| High-dose rifampicin for 3 months after culture conversion for drug-susceptible pulmonary tuberculosis |
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Nakwon Kwak1,2, Joong-Yub Kim1,2, Hyung-Jun Kim2,3, Byoung-Soo Kwon2,3, Jae Ho Lee2,3, Jeongha Mok4, Yong-Soo Kwon5, Young Ae Kang6, Youngmok Park6, Ji Yeon Lee7, Doosoo Jeon8, Jung-Kyu Lee2,9, Jeong Seong Yang10, Jake Whang10, Kyung Jong Kim10, Young Ran Kim11, Minkyoung Cheon12, Jiwon Park12, Seokyung Hahn12,13, Jae-Joon Yim1,2 |
1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
2Department of Internal Medicine, Seoul National University, Seoul National University College of Medicine, Seoul, South Korea
3Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
4Department of Internal Medicine, Pusan National University Hospital, Pusan National University School of Medicine, Busan, South Korea
5Department of Internal Medicine, Chonnam National University Hospital, Gwangju, South Korea
6Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Medical Center, Seoul, South Korea
8Department of Internal Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea
9Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, South Korea
10Research and Development Center, The Korean Institute of Tuberculosis, Cheongju, South Korea
11Clinical Research Section, International Tuberculosis Research Center, Seoul, South Korea
12Medical Research Collaborating Center, Seoul National University Hospital, Seoul, South Korea
13Division of Human System Medicine, Seoul National University College of Medicine, Seoul, South Korea |
Correspondence:
Jae-Joon Yim, Tel: 82-2-2072-2059, Fax: 82-2-762-9662,
Email: yimjj@snu.ac.kr
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Received: 12 July 2024 • Revised: 12 September 2024 • Accepted: 25 September 2024 |
| 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.
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.
Conclusions
The shorter high-dose rifampicin regimen failed to demonstrate non-inferiority but had an acceptable safety profile.
Trial registration
ClinicalTrials.gov NCT04485156 |
| Key Words:
High-dose rifampicin, tuberculosis, treatment shortening |
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