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

Seoul National University

Status and phase

Completed

Phase 2

Conditions

Tuberculosis, Multidrug-Resistant

Treatments

Drug: Linezolid

Drug: Levofloxacin

Drug: Pyrazinamide

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

Drug: Delamanid

Study type

Interventional

Funder types

Other

Identifiers

NCT02619994

MDR-END

Details and patient eligibility

About

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.

Full 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).

Enrollment

214 patients

Sex

All

Ages

19 to 85 years old

Volunteers

No Healthy Volunteers

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

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

214 participants in 2 patient groups

Control Arm

Active Comparator group

Description:

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

Treatment:

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

Experimental Arm

Experimental group