Treatment Shortening of MDR-TB Using Existing and New Drugs

NCT02619994 | Completed Phase 2 Results DMC

• 1 other identifier: MDR-END
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Tuberculosis, Multidrug-Resistant

Keywords

Multidrug-resistant tuberculosis; Linezolid; Delamanid; Multicenter randomized trial; Non-inferiority; Shorter regimen

Outcome Measures

Primary Outcomes (1)

• 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. (primary consideration for the modified intention-to-treat results)

  24 months after treatment start

Secondary Outcomes (8)

• Time to Sputum Culture Conversion After Treatment Start

  through study completion (24 months after treatment start)

• Sputum Culture Conversion Proportion

  At 2 months of treatment

• Treatment Success at the End of Treatment

  At the end of treatment

• Proportion of Reverting to Positive Sputum Culture After the End of Treatment

  At 24months after treatment start

• Treatment Success According to Pyrazinamide Resistance (1)

  At 24months after treatment start

Study Arms (2)

Control Arm

ACTIVE COMPARATOR

Regimen is the locally-used WHO-approved MDR-TB regimen in Korea based on 2014 Korean guideline of TB management. * Intensive phase regimen consists of four effective second-line anti-TB drugs (including injectables) and pyrazinamide. * Treatment duration: for at least 20 months

Drug: Locally-used WHO-approved MDR-TB regimen in Korea

Experimental Arm

EXPERIMENTAL

Regimen consists of only oral medication using delamanid, linezolid, levofloxacin, and pyrazinamide, for nine or twelve months depending on the time of sputum culture conversion to negative. * Delamanid (100 mg bid for the entire treatment period) * Linezolid (600mg/day for 2 months and 300mg/day afterwards until the end of treatment) * Levofloxacin (750 \~1000 mg/day) * Pyrazinamide (1000\~ 2000 mg/day)

Drug: Linezolid; Drug: Delamanid; Drug: Levofloxacin; Drug: Pyrazinamide

Interventions

Linezolid DRUG

Experimental Arm

Delamanid DRUG

Experimental Arm

Levofloxacin DRUG

Experimental Arm

Pyrazinamide DRUG

Experimental Arm

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

Control Arm

Eligibility Criteria

• Age: 19 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

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, 110-744, South Korea

Location

Related Publications (2)

• Mok J, Lee M, Kim DK, Kim JS, Jhun BW, Jo KW, Jeon D, Lee T, Lee JY, Park JS, Lee SH, Kang YA, Lee JK, Kwak N, Ahn JH, Shim TS, Kim SY, Kim S, Kim K, Seok KH, Yoon S, Kim YR, Kim J, Yim D, Hahn S, Cho SN, Yim JJ; MDR-END investigators. 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. Lancet. 2022 Oct 29;400(10362):1522-1530. doi: 10.1016/S0140-6736(22)01883-9.

  PMID: 36522208 DERIVED

• Lee M, Mok J, Kim DK, Shim TS, Koh WJ, Jeon D, Lee T, Lee SH, Kim JS, Park JS, Lee JY, Kim SY, Lee JH, Jo KW, Jhun BW, Kang YA, Ahn JH, Kim CK, Shin S, Song T, Shin SJ, Kim YR, Ahn H, Hahn S, Won HJ, Jang JY, Cho SN, Yim JJ. 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. 2019 Jan 16;20(1):57. doi: 10.1186/s13063-018-3053-1.

  PMID: 30651149 DERIVED

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant

Interventions

Linezolid; OPC-67683; Levofloxacin; Pyrazinamide

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrazines

Results Point of Contact

• Title: Dr. Prof. JJ Yim
• Organization: Seoul National University

yimjj@snu.ac.kr

82-02-1588-5700

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 24, 2015
• First Posted: December 2, 2015
• Study Start: January 1, 2016
• Primary Completion: June 1, 2021
• Study Completion: June 1, 2021
• Last Updated: January 3, 2025
• Results First Posted: January 3, 2025

Record last verified: 2024-11

Locations

KR (1)