MedPath

Linezolid Instead of Ethambutol in Treatment of Drug-susceptible Tuberculosis

Phase 2
Conditions
Pulmonary Tuberculosis Without Resistance to Rifampicin
Interventions
Registration Number
NCT01994460
Lead Sponsor
Seoul National University Hospital
Brief 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).

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
429
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).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 2 (experimental arm 1)LinezolidIsoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and linezolid (600 mg/day, 2 weeks)
Arm 3 (experimental arm 2)LinezolidIsoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and linezolid (600 mg/day, 4 weeks)
Arm 1 (control arm)EthambutolStandard treatment for drug-sensitive pulmonary TB using isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and ethambutol (2 months)
Primary Outcome Measures
NameTimeMethod
Sputum culture conversion rate on liquid mediaafter 2 months of treatment
Secondary Outcome Measures
NameTimeMethod
Sputum culture conversion rate on solid mediaafter 2 months of treatment
Time to sputum culture conversion (liquid and solid media)During 6 months of treatment
Cure rateAfter 6 months of treatment
Treatment success rateafter 6 months of treatment

Trial Locations

Locations (3)

Seoul National University Bundang Hospital

🇰🇷

Seongnam, Kyunggi, Korea, Republic of

National Medical Center

🇰🇷

Seoul, Korea, Republic of

SMG-SNU Boramae Medical Center

🇰🇷

Seoul, Korea, Republic of

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