Linezolid Instead of Ethambutol in Treatment of Drug-susceptible Tuberculosis

• ClinicalTrials.gov Identifier: NCT01994460
• Recruitment Status: Unknown
• First Posted: November 25, 2013
• Last Update Posted: December 30, 2014
• Sponsor: Seoul National University Hospital
• Collaborators: Ministry of Health & Welfare, Korea; SMG-SNU Boramae Medical Center; Seoul National University Bundang Hospital; Pfizer
• Information provided by (Responsible Party): Jae-Joon Yim, Seoul National University Hospital

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Pulmonary Tuberculosis Without Resistance to Rifampicin	Drug: Linezolid; Drug: Ethambutol	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 429 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Substitution of Ethambutol With Linezolid During the Intensive Phase of Treatment of Pulmonary Tuberculosis: A Prospective, Multicenter, Randomized, Open-label Phase II Trial
• Study Start Date: January 2014
• Estimated Primary Completion Date: December 2015
• Estimated Study Completion Date: June 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Sputum culture conversion rate on liquid media [ Time Frame: after 2 months of treatment ]

Secondary Outcome Measures :

1. Sputum culture conversion rate on solid media [ Time Frame: after 2 months of treatment ]
2. Time to sputum culture conversion (liquid and solid media) [ Time Frame: During 6 months of treatment ]
3. Cure rate [ Time Frame: After 6 months of treatment ]
4. Treatment success rate [ Time Frame: after 6 months of treatment ]

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Contacts

Contact: Jae-Joon Yim, MD; 82-2-2072-2059; yimjj@snu.ac.kr

Locations

Korea, Republic of

Seoul National University Bundang Hospital; Recruiting

Seongnam, Kyunggi, Korea, Republic of, 463-707

Contact: Jong Sun Park, MD 031-787-7054 jspark.im@gmail.com

Principal Investigator: Jong Sun Park, MD

National Medical Center; Recruiting

Seoul, Korea, Republic of, 100-799

Contact: Ji Yeon Lee, MD 82222607284 jedidiah125@gmail.com

Principal Investigator: Ji Yeon Lee, MD

SMG-SNU Boramae Medical Center; Recruiting

Seoul, Korea, Republic of, 156-707

Contact: Deog Kyeom Kim, MD 02-870-2228 kimdkmd@gmail.com

Principal Investigator: Deog Kyeom Kim, MD

Sponsors and Collaborators

Seoul National University Hospital

Ministry of Health & Welfare, Korea

SMG-SNU Boramae Medical Center

Seoul National University Bundang Hospital

Pfizer

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lee JK, Lee JY, Kim DK, Yoon HI, Jeong I, Heo EY, Park YS, Jo YS, Lee JH, Park SS, Park JS, Kim J, Lee SM, Joh JS, Lee CH, Lee J, Choi SM, Park JH, Lee SH, Cho YJ, Lee YJ, Kim SJ, Kwak N, Hwang YR, Kim H, Ki J, Lim JN, Choi HS, Lee M, Song T, Kim HS, Han J, Ahn H, Hahn S, Yim JJ. Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: a prospective, multicentre, randomised, open-label, phase 2 trial. Lancet Infect Dis. 2019 Jan;19(1):46-55. doi: 10.1016/S1473-3099(18)30480-8. Epub 2018 Nov 23.

Lee JY, Kim DK, Lee JK, Yoon HI, Jeong I, Heo E, Park YS, Lee JH, Park SS, Lee SM, Lee CH, Lee J, Choi SM, Park JS, Joh JS, Cho YJ, Lee YJ, Kim SJ, Hwang YR, Kim H, Ki J, Choi H, Han J, Ahn H, Hahn S, Yim JJ. Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: study protocol for a prospective, multicenter, randomized, open-label, phase II trial. Trials. 2017 Feb 13;18(1):68. doi: 10.1186/s13063-017-1811-0.

• Responsible Party: Jae-Joon Yim, Professor, Seoul National University Hospital
• ClinicalTrials.gov Identifier: NCT01994460
• Other Study ID Numbers: J-1310-026-523
• First Posted: November 25, 2013
• Last Update Posted: December 30, 2014
• Last Verified: December 2014

Keywords provided by Jae-Joon Yim, Seoul National University Hospital:

Tuberculosis

Additional relevant MeSH terms:

Tuberculosis; Tuberculosis, Pulmonary; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections; Linezolid; Ethambutol; Anti-Bacterial Agents; Anti-Infective Agents; Protein Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antitubercular Agents