Randomized Controlled Trial Multicenter Study
9 months of delamanid, linezolid, levofloxacin, and pyrazinamide versus conventional therapy for treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-END): a multicentre, randomised, open-label phase 2/3 non-inferiority trial in South Korea.
- Jeongha Mok, Myungsun Lee, Deog Kyeom Kim, Ju Sang Kim, Byung Woo Jhun, Kyung-Wook Jo, Doosoo Jeon, Taehoon Lee, Ji Yeon Lee, Jae Seuk Park, Seung Heon Lee, Young Ae Kang, Jung-Kyu Lee, Nakwon Kwak, Joong Hyun Ahn, Tae Sun Shim, Song Yee Kim, Seungmo Kim, Kyungjong Kim, Kwang-Hyuk Seok, Soyeong Yoon, Young Ran Kim, Jisu Kim, Dahae Yim, Seokyung Hahn, Sang Nae Cho, Jae-Joon Yim, and MDR-END investigators.
- Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Pusan National University Hospital, Busan, South Korea; Department of Internal Medicine, Pusan National University School of Medicine, Yangsan, South Korea.
- Lancet. 2022 Oct 29; 400 (10362): 152215301522-1530.
BackgroundWith 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.MethodsIn 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.FindingsBetween 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.Interpretation9-month treatment with oral delamanid, linezolid, levofloxacin, and pyrazinamide could represent a new treatment option for participants with fluoroquinolone-sensitive multidrug-resistant tuberculosis.FundingKorea Disease Control and Prevention Agency, South Korea.Copyright © 2022 Elsevier Ltd. All rights reserved.
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