Linezolid Instead of Ethambutol in Treatment of Drug-susceptible Tuberculosis

Study Overview
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Brief Summary
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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).

Official Title
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Substitution of Ethambutol With Linezolid During the Intensive Phase of Treatment of Pulmonary Tuberculosis: A Prospective, Multicenter, Randomized, Open-label Phase II Trial

Conditions
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Pulmonary Tuberculosis Without Resistance to Rifampicin

Intervention / Treatment
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* Drug: Linezolid
* Drug: Ethambutol


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1 (control arm)<br>Standard treatment for drug-sensitive pulmonary TB using isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and ethambutol (2 months) | Drug: Ethambutol<br> <br> |
| Experimental: Arm 2 (experimental arm 1)<br>Isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and linezolid (600 mg/day, 2 weeks) | Drug: Linezolid<br> <br> |
| Experimental: Arm 3 (experimental arm 2)<br>Isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and linezolid (600 mg/day, 4 weeks) | Drug: Linezolid<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sputum culture conversion rate on liquid media |  | after 2 months of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sputum culture conversion rate on solid media |  | after 2 months of treatment | 
| Time to sputum culture conversion (liquid and solid media) |  | During 6 months of treatment | 
| Cure rate |  | After 6 months of treatment | 
| Treatment success rate |  | after 6 months of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis