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Linezolid Instead of Ethambutol in Treatment of Drug-susceptible Tuberculosis

Primary Purpose

Pulmonary Tuberculosis Without Resistance to Rifampicin

Status

Unknown status

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Linezolid

Ethambutol

About this trial

This is an interventional treatment trial for Pulmonary Tuberculosis Without Resistance to Rifampicin focused on measuring Tuberculosis

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

Seoul National University Bundang HospitalRecruiting
National Medical CenterRecruiting
SMG-SNU Boramae Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Arm Label

Arm 1 (control arm)

Arm 2 (experimental arm 1)

Arm 3 (experimental arm 2)

Arm Description

Standard treatment for drug-sensitive pulmonary TB using isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and ethambutol (2 months)

Isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and linezolid (600 mg/day, 2 weeks)

Isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and linezolid (600 mg/day, 4 weeks)

Outcomes

Primary Outcome Measures

Sputum culture conversion rate on liquid media

Secondary Outcome Measures

Sputum culture conversion rate on solid media

Time to sputum culture conversion (liquid and solid media)

Cure rate

Treatment success rate

Full Information

NCT ID

NCT01994460

First Posted

November 13, 2013

Last Updated

December 27, 2014

Sponsor

Seoul National University Hospital

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT01994460

Brief Title

Linezolid Instead of Ethambutol in Treatment of Drug-susceptible Tuberculosis

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 Type

Interventional

2. Study Status

Record Verification Date

December 2014

Overall Recruitment Status

Unknown status

Study Start Date

January 2014 (undefined)

Primary Completion Date

December 2015 (Anticipated)

Study Completion Date

June 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Seoul National University Hospital

Collaborators

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

4. Oversight

Data Monitoring Committee

Yes

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pulmonary Tuberculosis Without Resistance to Rifampicin

Keywords

Tuberculosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

429 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm 1 (control arm)

Arm Type

Active Comparator

Arm Description

Standard treatment for drug-sensitive pulmonary TB using isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and ethambutol (2 months)

Arm Title

Arm 2 (experimental arm 1)

Arm Type

Experimental

Arm Description

Isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and linezolid (600 mg/day, 2 weeks)

Arm Title

Arm 3 (experimental arm 2)

Arm Type

Experimental

Arm Description

Isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and linezolid (600 mg/day, 4 weeks)

Intervention Type

Drug

Intervention Name(s)

Linezolid

Intervention Type

Drug

Intervention Name(s)

Ethambutol

Primary Outcome Measure Information:

Title

Sputum culture conversion rate on liquid media

Time Frame

after 2 months of treatment

Secondary Outcome Measure Information:

Title

Sputum culture conversion rate on solid media

Time Frame

after 2 months of treatment

Title

Time to sputum culture conversion (liquid and solid media)

Time Frame

During 6 months of treatment

Title

Cure rate

Time Frame

After 6 months of treatment

Title

Treatment success rate

Time Frame

after 6 months of treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jae-Joon Yim, MD

Phone

82-2-2072-2059

yimjj@snu.ac.kr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jae-Joon Yim, MD

Organizational Affiliation

Seoul National University Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Seoul National University Bundang Hospital

City

Seongnam

State/Province

Kyunggi

ZIP/Postal Code

463-707

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jong Sun Park, MD

Phone

031-787-7054

jspark.im@gmail.com

First Name & Middle Initial & Last Name & Degree

Jong Sun Park, MD

Facility Name

National Medical Center

City

Seoul

ZIP/Postal Code

100-799

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ji Yeon Lee, MD

Phone

82222607284

jedidiah125@gmail.com

First Name & Middle Initial & Last Name & Degree

Ji Yeon Lee, MD

Facility Name

SMG-SNU Boramae Medical Center

City

Seoul

ZIP/Postal Code

156-707

Country

Korea, Republic of

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Deog Kyeom Kim, MD

Phone

02-870-2228

kimdkmd@gmail.com

First Name & Middle Initial & Last Name & Degree

Deog Kyeom Kim, MD

12. IPD Sharing Statement

Citations:

PubMed Identifier

30477961

Citation

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.

Results Reference

derived

PubMed Identifier

28193240

Citation

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.

Results Reference

derived

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Linezolid Instead of Ethambutol in Treatment of Drug-susceptible Tuberculosis

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