• Myungsun Lee, Jeongha Mok, Deog Kyeom Kim, Tae Sun Shim, Won-Jung Koh, Doosoo Jeon, Taehoon Lee, Seung Heon Lee, Ju Sang Kim, Jae Seuk Park, Ji Yeon Lee, Song Yee Kim, Jae Ho Lee, Kyung-Wook Jo, Byung Woo Jhun, Young Ae Kang, Joong Hyun Ahn, Chang-Ki Kim, Soyoun Shin, Taeksun Song, Sung Jae Shin, Young Ran Kim, Heejung Ahn, Seokyung Hahn, Ho Jeong Won, Ji Yeon Jang, Sang Nae Cho, and Jae-Joon Yim.
• Clinical Research Section, International Tuberculosis Research Center, 247, Jangchungdan-ro, Jung-gu, Seoul, 04564, Republic of Korea.
• Trials. 2019 Jan 16; 20 (1): 57.

BackgroundTreatment success rates of multidrug-resistant tuberculosis (MDR-TB) remain unsatisfactory, and long-term use of second-line anti-TB drugs is accompanied by the frequent occurrence of adverse events, low treatment compliance, and high costs. The development of new efficient regimens with shorter treatment durations for MDR-TB will solve these issues and improve treatment outcomes.MethodsThis study is a phase II/III, multicenter, randomized, open-label clinical trial of non-inferiority design comparing a new regimen to the World Health Organization-endorsed conventional regimen for fluoroquinolone-sensitive MDR-TB. The control arm uses a conventional treatment regimen with second-line drugs including injectables for 20-24 months. The investigational arm uses a new shorter regimen including delamanid, linezolid, levofloxacin, and pyrazinamide for 9 or 12 months depending on time to sputum culture conversion. The primary outcome is the treatment success rate at 24 months after treatment initiation. Secondary outcomes include time to sputum culture conversion on liquid and solid media, proportions of sputum culture conversion on liquid media after 2 and 6 months of treatment, treatment success rate according to pyrazinamide resistance, and occurrence of adverse events grade 3 and above as evaluated by the Common Terminology Criteria for Adverse Events. Based on an α = 0.025 level of significance (one-sided test), a power of 80%, and a < 10% difference in treatment success rate between the control and investigational arms (80% vs. 70%) when the anticipated actual success rate in the treatment group is assumed to be 90%, the number of participants needed per arm to show non-inferiority of the investigational regimen was calculated as 48. Additionally, assuming the proportion of fluoroquinolone-susceptible MDR-TB among participants as 50%, and 5% loss to follow-up, the number of participants is calculated as N/( 0.50 × 0.95), resulting in 102 persons per group (204 in total).DiscussionThis trial will reveal the effectiveness and safety of a new shorter regimen comprising four oral drugs, including delamanid, linezolid, levofloxacin, and pyrazinamide, for the treatment of fluoroquinolone-sensitive MDR-TB. Results from this trial will provide evidence for adopting a shorter and more convenient treatment regimen for MDR-TB.Trial RegistrationClincalTrials.gov, NCT02619994 . Registered on 2 December 2015.

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