Delamanid, linezolid, levofloxacin, and pyrazinamide for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (Treatment Shortening of MDR-TB Using Existing and New Drugs, MDR-END): study protocol for a phase II/III, multicenter, randomized, open-label clinical trial

Trials

Sang Nae Cho¹  Myungsun Lee¹  Young Ran Kim¹  Sung Jae Shin²  Ju Sang Kim³  Joong Hyun Ahn³  Seung Heon Lee⁴  Taehoon Lee⁵  Tae Sun Shim⁶  Kyung-Wook Jo⁶  Jae Seuk Park⁷  Ji Yeon Lee⁸  Doosoo Jeon⁹  Deog Kyeom Kim^1,10  Jae Ho Lee^1,11  Jae-Joon Yim^1,12  Byung Woo Jhun^1,13  Won-Jung Koh^1,13  Jeongha Mok^1,14  Young Ae Kang^1,15  Song Yee Kim^1,15  Taeksun Song^1,16  Soyoun Shin^1,17  Heejung Ahn^1,18  Ji Yeon Jang^1,18  Ho Jeong Won^1,18  Seokyung Hahn^1,18  Chang-Ki Kim^1,19 

[1] Clinical Research Section, International Tuberculosis Research Center;Department of Microbiology, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine;Department of Pulmonary and Critical Care Medicine, Department of Internal Medicine, The Catholic University of Korea, Incheon St. Mary’s Hospital;Department of Pulmonology, Korea University Ansan Hospital;Department of Pulmonology, Ulsan University Hospital, University of Ulsan College of Medicine;Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center;Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Dankook University Hospital;Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Medical Center;Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital;Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Boramae Medical Center;Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital;Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine;Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine;Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Pusan National University Hospital;Division of Pulmonology, Department of Internal Medicine, Institute of Chest Diseases, Severance Hospital, Yonsei University College of Medicine;Institute of Infectious Disease and Molecular Medicine, University of Cape Town;Laboratory Medicine Center, The Korean Institute of Tuberculosis;Medical Research Collaborating Center, Seoul National University Hospital;Seoul Clinical Laboratories;

关键词: Tuberculosis;    Multidrug-resistant tuberculosis;    Multicenter randomized trial;    Non-inferiority;    Shorter regimen;    Delamanid;   

DOI  :  10.1186/s13063-018-3053-1

来源: DOAJ

【 摘 要 】

Abstract Background Treatment 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. Methods This 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). Discussion This 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 registration ClincalTrials.gov, NCT02619994. Registered on 2 December 2015.

【 授权许可】

Unknown