한빛사 논문
- 조회1,106
Prof Jeongha Mok, MD †1,2, Myungsun Lee, MD†3, Prof Deog Kyeom Kim, MD4,5, Prof Ju Sang Kim, MD6, Prof Byung Woo Jhun, MD7, Prof Kyung-Wook Jo, MD8, Prof Doosoo Jeon, MD9,10, Prof Taehoon Lee, MD11, Ji Yeon Lee12, Prof Jae Seuk Park, MD13, Prof Seung Heon Lee, MD14, Prof Young Ae Kang, MD15, Prof Jung-Kyu Lee, MD4, Prof Nakwon Kwak, MD16, Prof Joong Hyun Ahn, MD6, Prof Tae Sun Shim, MD11, Prof Song Yee Kim, MD15, Seungmo Kim, MA17, Kyungjong Kim, PhD18,19, Kwang-Hyuk Seok, PhD17, Soyeong Yoon, BS20, Young Ran Kim, RN20, Jisu Kim, BS21, Dahae Yim21, Prof Seokyung Hahn, PhD21,22, Sang Nae Cho, PhD20, Prof Jae-Joon Yim, MD5,16, on behalf of theMDR-END investigators
1Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Pusan National University Hospital, Busan, South Korea
2Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, South Korea
3Division of Clinical Research, International Tuberculosis Research Centre, Seoul, South Korea
4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Centre, Seoul, South Korea
5Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea
6Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, Incheon St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
7Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, South Korea
8Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
9Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, South Korea
10Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, South Korea
11Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea
12Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Medical Centre, Seoul, South Korea
13Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Dankook University Hospital, Cheonan, South Korea
14Department of Pulmonology, Korea University Ansan Hospital, Ansan, South Korea
15Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
16Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea
17Department of Laboratory Medicine, The Korean Institute of Tuberculosis, Cheongju, South Korea
18Department of R&D, The Korean Institute of Tuberculosis, Cheongju, South Korea
19DNA Analysis Division, Seoul Institute, National Forensic Service, Seoul, South Korea
20Division of Clinical Research, International Tuberculosis Research Centre, Seoul, South Korea
21Medical Research Collaborating Centre, Seoul National University Hospital, Seoul, South Korea
22Department of Human Systems Medicine, Seoul National University College of Medicine, Seoul, South Korea
† Contributed equally
Correspondence to: Prof Jae-Joon Yim
Abstract
Background
With the introduction of new anti-tuberculosis drugs, all-oral regimens with shorter treatment durations for multidrug-resistant tuberculosis have been anticipated. We aimed to investigate whether a new all-oral regimen was non-inferior to the conventional regimen including second-line anti-tuberculosis drugs for 20–24 months in the treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis.
Methods
In this multicentre, randomised, open-label phase 2/3 non-inferiority trial, we enrolled men and women aged 19–85 years with multidrug-resistant tuberculosis confirmed by phenotypic or genotypic drug susceptibility tests or rifampicin-resistant tuberculosis by genotypic tests at 12 participating hospitals throughout South Korea. Participants with fluoroquinolone-resistant multidrug-resistant tuberculosis were excluded. Participants were randomly assigned (1:1) to two groups using a block randomisation, stratified by the presence of diabetes and cavitation on baseline chest radiographs. The investigational group received delamanid, linezolid, levofloxacin, and pyrazinamide for 9 months, and the control group received a conventional 20–24-month regimen, according to the 2014 WHO guidelines. The primary outcome was the treatment success rate at 24 months after treatment initiation in the modified intention-to-treat population and the per-protocol population. Participants who were “cured” and “treatment completed” were defined as treatment success following the 2014 WHO guidelines. Non-inferiority was confirmed if the lower limit of a 97·5% one-sided CI of the difference between the groups was greater than −10%. Safety data were collected for 24 months in participants who received a predefined regimen at least once. This study is registered with ClinicalTrials.gov, NCT02619994.
Findings
Between March 4, 2016, and Sept 14, 2019, 214 participants were enrolled, 168 (78·5%) of whom were included in the modified intention-to-treat population. At 24 months after treatment initiation, 60 (70·6%) of 85 participants in the control group had treatment success, as did 54 (75·0%) of 72 participants in the shorter-regimen group (between-group difference 4·4% [97·5% one-sided CI –9·5% to ∞]), satisfying the predefined non-inferiority margin. No difference in safety outcomes was identified between the control group and the shorter-regimen group.
Interpretation
9-month treatment with oral delamanid, linezolid, levofloxacin, and pyrazinamide could represent a new treatment option for participants with fluoroquinolone-sensitive multidrug-resistant tuberculosis.
논문정보
- Research article
- 2022년 10월 (BRIC 등록일 2022-10-28)
- 국내 연구진
- 의약학 > 응용의학
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