Clinical trial NCT02619994: Treatment Shortening of MDR-TB Using Existing and New Drugs
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tuberculosis, Multidrug-Resistant
Keywords: Multidrug-resistant tuberculosis
Linezolid
Delamanid
Multicenter randomized trial
Non-inferiority
Shorter regimen
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Asan Medical Center
name: Dankook University
name: International Tuberculosis Research Center
name: Pusan National University Yangsan Hospital
name: Pusan National University Hospital
name: Samsung Medical Center
name: Severance Hospital
name: SMG-SNU Boramae Medical Center
name: Incheon St.Mary's Hospital
name: Ulsan University Hospital
name: Korean Institute of Tuberculosis
name: National Medical Center, Seoul
name: Korean Center for Disease Control and Prevention
name: Korea University Ansan Hospital
First posted: 2015-12-02
Enrollment: 214
Sex: ALL
Minimum age (years): 19
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Eligibility 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

Primary outcomes:
measure: Treatment Success Rate
timeFrame: 24 months after treatment start
Secondary outcomes:
measure: Time to Sputum Culture Conversion After Treatment Start
timeFrame: through study completion (24 months after treatment start)
measure: Sputum Culture Conversion Proportion
timeFrame: At 2 months of treatment
measure: Treatment Success at the End of Treatment
timeFrame: At the end of treatment
measure: Proportion of Reverting to Positive Sputum Culture After the End of Treatment
timeFrame: At 24months after treatment start
measure: Treatment Success According to Pyrazinamide Resistance (1)
timeFrame: At 24months after treatment start
measure: Proportion of Death Between the Control and Investigational Arms
timeFrame: At 24months after treatment start
measure: Sputum Culture Conversion Proportion
timeFrame: At 6 months of treatment start
measure: Treatment Success According to Pyrazinamide Resistance (2)
timeFrame: At 24 months after treatment start
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine
Study officials:
References:
citation: 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.