NCT01994460

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).

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
429

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jan 2014

Geographic Reach
1 country

3 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 13, 2013

Completed
12 days until next milestone

First Posted

Study publicly available on registry

November 25, 2013

Completed
1 month until next milestone

Study Start

First participant enrolled

January 1, 2014

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2015

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2016

Completed
Last Updated

December 30, 2014

Status Verified

December 1, 2014

Enrollment Period

1.9 years

First QC Date

November 13, 2013

Last Update Submit

December 27, 2014

Conditions

Pulmonary Tuberculosis Without Resistance to Rifampicin

Keywords

Tuberculosis

Outcome Measures

Primary Outcomes (1)

  • Sputum culture conversion rate on liquid media

    after 2 months of treatment

Secondary Outcomes (4)

  • 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

Study Arms (3)

Arm 1 (control arm)

ACTIVE COMPARATOR

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

Drug: Ethambutol

Arm 2 (experimental arm 1)

EXPERIMENTAL

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

Drug: Linezolid

Arm 3 (experimental arm 2)

EXPERIMENTAL

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

Drug: Linezolid

Interventions

LinezolidDRUG
Arm 2 (experimental arm 1)Arm 3 (experimental arm 2)
EthambutolDRUG
Arm 1 (control arm)

Eligibility Criteria

Age20 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Seoul National University Bundang Hospital

Seongnam, Kyunggi, 463-707, South Korea

RECRUITING

National Medical Center

Seoul, Seoul, 100-799, South Korea

RECRUITING

SMG-SNU Boramae Medical Center

Seoul, Seoul, 156-707, South Korea

RECRUITING

Related Publications (2)

  • 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.

    PMID: 30477961DERIVED

  • 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.

    PMID: 28193240DERIVED

MeSH Terms

Conditions

Tuberculosis

Interventions

LinezolidEthambutol

Condition Hierarchy (Ancestors)

Mycobacterium InfectionsActinomycetales InfectionsGram-Positive Bacterial InfectionsBacterial InfectionsBacterial Infections and MycosesInfections

Intervention Hierarchy (Ancestors)

AcetamidesAmidesOrganic ChemicalsAcetatesAcids, AcyclicCarboxylic AcidsOxazolidinonesOxazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsEthylenediaminesDiaminesPolyaminesAmines

Study Officials

  • Jae-Joon Yim, MD

    Seoul National University Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Jae-Joon Yim, MD

CONTACT

82-2-2072-2059yimjj@snu.ac.kr

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

November 13, 2013

First Posted

November 25, 2013

Study Start

January 1, 2014

Primary Completion

December 1, 2015

Study Completion

June 1, 2016

Last Updated

December 30, 2014

Record last verified: 2014-12

Locations

KR(3)