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Completed

NCT Number: NCT02619994

Treatment Shortening of MDR-TB Using Existing and New Drugs

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.

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Key information

Conditions

Tuberculosis, Multidrug-Resistant Actinomycetales Infections Bacterial Infections Bacterial Infections and Mycoses Gram-Positive Bacterial Infections Infections Mycobacterium Infections Tuberculosis

Age range

19 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

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

About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Linezolid

Drug

Delamanid

Drug

Levofloxacin

Drug

Pyrazinamide

Drug

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

Drug

Primary outcomes

  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.

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

Secondary outcomes

  1. Time to Sputum Culture Conversion After Treatment Start

    Time frame: through study completion (24 months after treatment start)

    To determine whether time to sputum culture conversion after treatment start is statistically 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 of treatment

    Culture conversion rate at month 2 of treatment in participants with positive baseline sputum culture (liquid media).

  3. Treatment Success at the End of Treatment

    Time frame: At the end of treatment

    Treatment success rate at the end of treatment.

    • control arm (20-24 months)
    • experimental arm (40 or 52 weeks)

  4. Proportion of Reverting to Positive Sputum Culture After the End of Treatment

    Time frame: At 24months after treatment start

    The proportion of patients who experienced a reversion between the end of treatment and up to 24 months after treatment start

  5. Treatment Success According to Pyrazinamide Resistance (1)

    Time frame: At 24months after treatment start

    Treatment success rate of participants with pyrazinamide resistance in the mITT analysis

  6. Proportion of Death Between the Control and Investigational Arms

    Time frame: At 24months after treatment start

    The proportion of participants who died in the control and experimental arm mITT population

  7. Sputum Culture Conversion Proportion

    Time frame: At 6 months of treatment start

    Culture conversion rate at month 6 of treatment in participants with positive baseline sputum culture (liquid media).

  8. Treatment Success According to Pyrazinamide Resistance (2)

    Time frame: At 24 months after treatment start

    Treatment success rate of participants without pyrazinamide resistance in the mITT analysis

Sponsors and collaborators

Lead sponsor

Seoul National University Hospital

Other

Collaborators

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

Registry information

Official study 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

Acronym: MDR-END

Important dates

Study start
2016
Primary completion
2021
Study completion
2021
First posted
Dec 2, 2015
Registry last updated
Jan 3, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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