Linezolid Instead of Ethambutol in Treatment of Drug-susceptible Tuberculosis

• Status: Unknown status
• Trial end date: 2016-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The current standard short-course treatment for pulmonary TB requires 6 months to complete. This long duration of treatment increases the likelihood of side effects while decreasing patients' adherence to anti-TB drugs. Linezolid showed considerable efficacy against refractory multidrug-resistant TB. Considering the marked anti-TB effects of linezolid as well as the possible adverse effects of its long-term use, it is rational to use linezolid instead of ethambutol for the first 4 weeks of treatment for drug-susceptible pulmonary TB. Through randomized controlled trial, the investigators will evaluate the hypothesis that the use of linezolid instead of ethambutol will increase the sputum culture conversion rate by 15% after 2 months of treatment. Patients with TB without resistance to rifampicin will be randomized to the following three arms at a 1:1:1 ratio: Arma 1 (control arm), Arm 2 (linezolid for 2 weeks instead of ethambutol), Arm 3 (linezolid for 4 weeks instead of ethambutol)Primary outcome will be sputum culture conversion rate after 2 months of treatment (liquid media).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Seoul National University Hospital
• Collaborators: Ministry of Health & Welfare, Korea; Pfizer; Seoul National University Bundang Hospital; SMG-SNU Boramae Medical Center
• Treatments: Ethambutol; Linezolid

Criteria

Inclusion Criteria:

• Males and females aged from 20 to 80 years (20- and 80-year-old patients can participate).

• Documented sputum Xpert MTB/RIF assay-positive pulmonary TB at screening.

• On current TB therapy (if any) for ≤14 days at the time of enrollment.

Exclusion Criteria:

• Patients with HIV/AIDS.

• Females of childbearing potential, who are pregnant, breastfeeding, or unwilling to avoid pregnancy.

• Any of the following:

i.Absolute neutrophil count of <2000 cells/mL. ii.White blood cell count (WBC) of <3000/μL. iii.Hemoglobin concentration of <7.0 g/dL. iv.Serum creatinine level of >2.0 mg/dL. v.Aspartate aminotransferase (AST or SGOT) of >100 IU/L. vi.Alanine aminotransferase (ALT or SGPT) of >100 IU/L. vii.Total bilirubin level of >2.0 mg/dL. viii.History of optic neuritis or peripheral neuropathy. ix.Other significant laboratory abnormalities (i.e., absolute neutrophil count, creatinine level).

x.The need for ongoing therapy with SSRIs, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine, buspirone, monoamine oxidase inhibitors (MAOIs), sympathomimetic agents (e.g., pseudoephedrine), vasopressive agents (e.g., epinephrine, norepinephrine), or dopaminergic agents (e.g., dopamine, dobutamine).