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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

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Title: 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: 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
Contributors: 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, Kang, Young Ae
Source: The Lancet. 400:1522-1530
Publisher Information: Elsevier BV, 2022.
Publication Year: 2022
Subject Terms: Male, 0301 basic medicine, Antitubercular Agents, Pyrazinamide* / therapeutic use, Levofloxacin, 03 medical and health sciences, 0302 clinical medicine, Drug Therapy, Tuberculosis, Multidrug-Resistant, Tuberculosis, Humans, Levofloxacin / therapeutic use, Antitubercular Agents / therapeutic use, Linezolid / therapeutic use, Linezolid, 16. Peace & justice, Pyrazinamide, 3. Good health, Multidrug-Resistant* / drug therapy, Treatment Outcome, Combination, Fluoroquinolones / therapeutic use, Female, Drug Therapy, Combination, Fluoroquinolones
Description: 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.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.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.9-month treatment with oral delamanid, linezolid, levofloxacin, and pyrazinamide could represent a new treatment option for participants with fluoroquinolone-sensitive multidrug-resistant tuberculosis.Korea Disease Control and Prevention Agency, South Korea.
Document Type: Article
Language: English
ISSN: 0140-6736
DOI: 10.1016/s0140-6736(22)01883-9
Access URL: https://pubmed.ncbi.nlm.nih.gov/36522208
Rights: Elsevier TDM
CC BY NC ND
Accession Number: edsair.doi.dedup.....41f59c24f5be888328d772542cac27d9
Database: OpenAIRE
Description
Abstract: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.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.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.9-month treatment with oral delamanid, linezolid, levofloxacin, and pyrazinamide could represent a new treatment option for participants with fluoroquinolone-sensitive multidrug-resistant tuberculosis.Korea Disease Control and Prevention Agency, South Korea.
ISSN:01406736
DOI:10.1016/s0140-6736(22)01883-9