Treatment Shortening of MDR-TB Using Existing and New Drugs

Tuberculosis, Multidrug-Resistant Clinical Trial

— MDR-END  

Official title:

Delamanid, Linezolid, Levofloxacin, and Pyrazinamide for the Treatment of Patients With Fluoroquinolone-sensitive MDR-TB: A Phase 2/3, Multicenter, Randomized, Open-label, Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02619994
• Other study ID #: MDR-END
• Status: Recruiting
• Phase: Phase 2
• Start date: January 2016
• Est. completion date: June 2021

Study information

• Verified date: January 2019
• Source: Seoul National University Hospital
• Contact: Jae-Joon Yim, MD
• Phone: +82-2-2072-2059
• Email: yimjj[@]snu.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the efficacy of a 'new treatment regimen including delamanid, linezolid, levofloxacin, and pyrazinamide for nine or twelve months (investigational arm)' and 'the standard treatment regimen including injectables for 20 to 24 months (control arm)' for treating fluoroquinolone-sensitive multidrug-resistant tuberculosis.

Description:

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. The population number is calculated as 102 per group (204 in total).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 238
• Est. completion date: June 2021
• Est. primary completion date: June 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 85 Years

Eligibility

Inclusion Criteria:

• Males and females aged from 19 to 85 years

• Confirmed MDR-TB or RR-TB

• On current TB therapy for =14 days at the time of enrollment.

Exclusion Criteria:

• Known any quinolone-resistant MDR-TB

• Known XDR-TB

• who are pregnant or who are unwilling to use proper contraceptives at childbearing age

• Medical history of galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption

• The need for ongoing use of prohibited drugs while on study drugs

• History of optic neuropathy or peripheral neuropathy

• With any of the following test results: i.Absolute neutrophil count < 2000 cells/mL, ii.White blood cell count (WBC) < 3.0 X 103/µL, iii.Hemoglobin < 7.0 g/dL, iv.Serum creatinine > 2.0 mg/dL, v.Aspartate aminotransferase (AST or SGOT) >100 IU/L, vi.Alanine aminotransferase (ALT or SGPT) >100 IU/L, vii.Total bilirubin > 2.0 mg/dL, viii.Albumin < 2.8g/dL, ix.QTcF > 500ms

• History of hypersensitivity reaction to the study drugs

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculosis, Multidrug-Resistant

Intervention

Drug:
• Linezolid

• Delamanid

• Levofloxacin

• Pyrazinamide

• Locally-used WHO-approved MDR-TB regimen in Korea

Locations

Country	Name	City	State
Korea, Republic of	Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine	Seoul

Sponsors (15)

Lead Sponsor

Collaborator

Seoul National University Hospital

Asan Medical Center, Dankook University, Incheon St.Mary's Hospital, International Tuberculosis Research Center, Korea University, Korean Center for Disease Control and Prevention, Korean Institute of Tuberculosis, National Medical Center, Seoul, Pusan National University Hospital, Pusan National University Yangsan Hospital, Samsung Medical Center, Severance Hospital, SMG-SNU Boramae Medical Center, Ulsan University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment success rate	To test for non-inferiority of the investigational arm, when the lower limit of the one-sided 97.5% confidence interval of the difference (PT - PC) between investigational and control arms is larger than the non-inferiority margin of - 10%, it will be concluded that the treatment success rate of the investigational arm shows non-inferiority to the treatment success rate of the control arm.	24 months after treatment start
Secondary	Time to sputum culture conversion after treatment start	To determine whether time to sputum culture conversion after treatment start is statis- tically different between the control and investigational arms, the median time will be estimated in each group using the Kaplan-Meier method, and the difference in the distribution of time to culture conversion of the two arms will be compared using the log-rank test.	through study completion, 24 months after enrollment
Secondary	Sputum culture conversion proportion		At 2 months or 6 months of treatment
Secondary	Treatment success		At 24months after enrollment
Secondary	proportion of reverting to positive sputum culture after the end of treatment		At 24months after enrollment
Secondary	Treatment success according to pyrazinamide resistance		At 24months after enrollment
Secondary	proportion of death between the control and investigational arms		At 24months after enrollment