Treatment Shortening of MDR-TB Using Existing and New Drugs

Phase 2CompletedNCT02619994

Seoul National University Hospital214 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

214

Conditions

Tuberculosis, Multidrug-Resistant

Interventions

LinezolidDRUG

DelamanidDRUG

LevofloxacinDRUG

PyrazinamideDRUG

Eligibility

Sex: ALLMin age: 19 YearsMax age: 85 Years

Medical Language ↔ Plain English

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

Locations (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, South Korea

Outcomes

Primary Outcomes

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)

Time frame: 24 months after treatment start

Secondary Outcomes

Time to Sputum Culture Conversion 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.

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

Sputum Culture Conversion Proportion

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

Time frame: At 2 months of treatment

Treatment Success at the End of Treatment

Treatment success rate at the end of treatment. * control arm (20-24 months) * experimental arm (40 or 52 weeks)

Time frame: At the end of treatment

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

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

Time frame: At 24months after treatment start

Data from ClinicalTrials.gov

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