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Treatment Shortening of MDR-TB Using Existing and New Drugs (MDR-END)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02619994
Recruitment Status : Unknown
Verified January 2019 by Jae-Joon Yim, Seoul National University Hospital.
Recruitment status was:  Recruiting
First Posted : December 2, 2015
Last Update Posted : February 4, 2019
Sponsor:
Collaborators:
Asan Medical Center
Dankook University
International Tuberculosis Research Center
Pusan National University Yangsan Hospital
Pusan National University Hospital
Samsung Medical Center
Severance Hospital
SMG-SNU Boramae Medical Center
Incheon St.Mary's Hospital
Ulsan University Hospital
Korean Institute of Tuberculosis
National Medical Center, Seoul
Korean Center for Disease Control and Prevention
Korea University
Information provided by (Responsible Party):
Jae-Joon Yim, Seoul National University Hospital

Study Description
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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.

Condition or disease Intervention/treatment Phase
Tuberculosis, Multidrug-Resistant Drug: Linezolid Drug: Delamanid Drug: Levofloxacin Drug: Pyrazinamide Drug: Locally-used WHO-approved MDR-TB regimen in Korea Phase 2

Detailed 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).
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 238 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : January 2016
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Control Arm

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: Experimental Arm

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


Outcome Measures
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Primary Outcome Measures :
  1. Treatment success rate [ Time Frame: 24 months after treatment start ]
    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.


Secondary Outcome Measures :
  1. Time to sputum culture conversion after treatment start [ Time Frame: through study completion, 24 months after enrollment ]
    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.

  2. Sputum culture conversion proportion [ Time Frame: At 2 months or 6 months of treatment ]
  3. Treatment success [ Time Frame: At 24months after enrollment ]
  4. proportion of reverting to positive sputum culture after the end of treatment [ Time Frame: At 24months after enrollment ]
  5. Treatment success according to pyrazinamide resistance [ Time Frame: At 24months after enrollment ]
  6. proportion of death between the control and investigational arms [ Time Frame: At 24months after enrollment ]

Eligibility Criteria
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Ages Eligible for Study:   19 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02619994


Contacts
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Contact: Jae-Joon Yim, MD +82-2-2072-2059 yimjj@snu.ac.kr

Locations
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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 Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Jae-Joon Yim, MD    +82-2-2072-2059    yimjj@snu.ac.kr   
Sponsors and Collaborators
Seoul National University Hospital
Asan Medical Center
Dankook University
International Tuberculosis Research Center
Pusan National University Yangsan Hospital
Pusan National University Hospital
Samsung Medical Center
Severance Hospital
SMG-SNU Boramae Medical Center
Incheon St.Mary's Hospital
Ulsan University Hospital
Korean Institute of Tuberculosis
National Medical Center, Seoul
Korean Center for Disease Control and Prevention
Korea University
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Jae-Joon Yim, Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT02619994    
Other Study ID Numbers: MDR-END
First Posted: December 2, 2015    Key Record Dates
Last Update Posted: February 4, 2019
Last Verified: January 2019
Keywords provided by Jae-Joon Yim, Seoul National University Hospital:
Multidrug-resistant tuberculosis
Linezolid
Delamanid
 Multicenter randomized trial
Non-inferiority
Shorter regimen
Additional relevant MeSH terms:
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Tuberculosis
Tuberculosis, Multidrug-Resistant
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections
Levofloxacin
Linezolid
Pyrazinamide
Anti-Infective Agents, Urinary
 Anti-Infective Agents
Anti-Bacterial Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Protein Synthesis Inhibitors
Antitubercular Agents