Linezolid Instead of Ethambutol in Treatment of Drug-susceptible Tuberculosis

December 27, 2014 updated by: Jae-Joon Yim, Seoul National University Hospital

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

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).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

429

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 156-707
        • Recruiting
        • SMG-SNU Boramae Medical Center
        • Contact:
        • Principal Investigator:
          • Deog Kyeom Kim, MD
      • Seoul, Korea, Republic of, 100-799
        • Recruiting
        • National Medical Center
        • Contact:
        • Principal Investigator:
          • Ji Yeon Lee, MD
    • Kyunggi
      • Seongnam, Kyunggi, Korea, Republic of, 463-707
        • Recruiting
        • Seoul National University Bundang Hospital
        • Contact:
        • Principal Investigator:
          • Jong Sun Park, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seoul National University Hospital

Collaborators

Pfizer
Seoul National University Bundang Hospital
SMG-SNU Boramae Medical Center
Ministry of Health & Welfare, Korea

Investigators

  • Principal Investigator: Jae-Joon Yim, MD, Seoul National University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2014

Primary Completion (Anticipated)

December 1, 2015

Study Completion (Anticipated)

June 1, 2016

Study Registration Dates

First Submitted

November 13, 2013

First Submitted That Met QC Criteria

November 19, 2013

First Posted (Estimate)

November 25, 2013

Study Record Updates

Last Update Posted (Estimate)

December 30, 2014

Last Update Submitted That Met QC Criteria

December 27, 2014

Last Verified

December 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • J-1310-026-523

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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