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
- Authors
- Mok, Jeongha; Lee, Myungsun; Kim, Deog Kyeom; Kim, Ju Sang; Jhun, Byung Woo; Jo, Kyung-Wook; Jeon, Doosoo; Lee, Taehoon; Lee, Ji Yeon; Park, Jae Seuk; Lee, Seung Heon; Kang, Young Ae; Lee, Jung-Kyu; Kwak, Nakwon; Ahn, Joong Hyun; Shim, Tae Sun; Kim, Song Yee; Kim, Seungmo; Kim, Kyungjong; Seok, Kwang-Hyuk; Yoon, Soyeong; Kim, Young Ran; Kim, Jisu; Yim, Dahae; Hahn, Seokyung; Cho, Sang Nae; Yim, Jae-Joon
- Issue Date
- Oct-2022
- Publisher
- The Lancet Publishing Group
- Citation
- The Lancet, v.400, no.10362, pp 1522 - 1530
- Pages
- 9
- Indexed
- SCIE
SCOPUS
- Journal Title
- The Lancet
- Volume
- 400
- Number
- 10362
- Start Page
- 1522
- End Page
- 1530
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/62453
- DOI
- 10.1016/S0140-6736(22)01883-9
- ISSN
- 0140-6736
1474-547X
- 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.
Funding
Korea Disease Control and Prevention Agency, South Korea
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Collections - 2. Clinical Science > Department of Pulmonary, Allergy, and Critical Care Medicine > 1. Journal Articles
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