Clinical trial NCT01994460: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Pulmonary Tuberculosis Without Resistance to Rifampicin
Keywords: Tuberculosis
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Ministry of Health & Welfare, Korea
name: SMG-SNU Boramae Medical Center
name: Seoul National University Bundang Hospital
name: Pfizer
First posted: 2013-11-25
Enrollment: 429
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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).

Primary outcomes:
measure: Sputum culture conversion rate on liquid media
timeFrame: after 2 months of treatment
Secondary outcomes:
measure: Sputum culture conversion rate on solid media
timeFrame: after 2 months of treatment
measure: Time to sputum culture conversion (liquid and solid media)
timeFrame: During 6 months of treatment
measure: Cure rate
timeFrame: After 6 months of treatment
measure: Treatment success rate
timeFrame: after 6 months of treatment
Other outcomes:
Locations:
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Kyunggi
city: Seoul
country: Korea, Republic of
facility: National Medical Center
city: Seoul
country: Korea, Republic of
facility: SMG-SNU Boramae Medical Center
Study officials:
affiliation: Seoul National University Hospital
name: Jae-Joon Yim, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.