PMID- 28193240
OWN - NLM
STAT- MEDLINE
DCOM- 20180226
LR  - 20181113
IS  - 1745-6215 (Electronic)
IS  - 1745-6215 (Linking)
VI  - 18
IP  - 1
DP  - 2017 Feb 13
TI  - 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.
PG  - 68
LID - 10.1186/s13063-017-1811-0 [doi]
LID - 68
AB  - BACKGROUND: Linezolid, an oxazolidinone, substantially improves treatment 
      outcomes of multidrug-resistant tuberculosis and extensively drug-resistant 
      tuberculosis. We started a trial to test whether the use of linezolid instead of 
      ethambutol could increase the rate of sputum culture conversion as of 8 weeks of 
      treatment in patients with drug-susceptible tuberculosis. METHODS/DESIGN: This is 
      a phase II, multicenter, randomized study with three arms. We are enrolling 
      patients with pulmonary tuberculosis without rifampicin resistance screened by 
      the Xpert MTB/RIF(R) assay. The standard treatment arm uses isoniazid (6 months), 
      rifampicin (6 months), pyrazinamide (2 months), and ethambutol (2 months). 
      Experimental arm 1 uses linezolid (600 mg/day) for 4 weeks instead of ethambutol. 
      Experimental arm 2 uses linezolid (600 mg/day) for 2 weeks instead of ethambutol. 
      The primary outcome is the sputum culture conversion rate on liquid media after 2 
      months of treatment. Secondary outcomes include the sputum culture conversion 
      rate on solid media after 2 months of treatment, time to sputum culture 
      conversion on liquid and solid media, cure rate, and treatment success rate. The 
      frequencies of total adverse events (AEs) and serious AEs will be described and 
      documented. Based on an alpha = 0.05 level of significance, a power of 85%, a 15% 
      difference in the culture conversion rate after 2 months between the control arm 
      and experimental arm 1 (75% vs. 90%), a 10% default (loss to follow-up) rate, and 
      a 10% culture failure, the required number per arm was calculated to be 143 (429 
      in total). DISCUSSION: This trial will reveal the effectiveness and safety of 2 
      or 4 weeks of use of linezolid instead of ethambutol for patients with 
      drug-susceptible pulmonary tuberculosis. If a new regimen including linezolid 
      shows a higher culture conversion rate by week 8, and is safe, it could be tested 
      as a 4-month antituberculosis treatment regimen in the future. TRIAL 
      REGISTRATION: ClincalTrials.gov, NCT01994460 . Registered on 13 November 2013.
FAU - Lee, Ji Yeon
AU  - Lee JY
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, National Medical Center, Seoul, Republic of Korea.
FAU - Kim, Deog Kyeom
AU  - Kim DK
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of 
      Korea.
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Seoul, Republic of Korea.
FAU - Lee, Jung-Kyu
AU  - Lee JK
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of 
      Korea.
FAU - Yoon, Ho Il
AU  - Yoon HI
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of 
      Korea.
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Seoul, Republic of Korea.
FAU - Jeong, Ina
AU  - Jeong I
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, National Medical Center, Seoul, Republic of Korea.
FAU - Heo, Eunyoung
AU  - Heo E
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of 
      Korea.
FAU - Park, Young Sik
AU  - Park YS
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
FAU - Lee, Jae Ho
AU  - Lee JH
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of 
      Korea.
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Seoul, Republic of Korea.
FAU - Park, Sung Soo
AU  - Park SS
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of 
      Korea.
FAU - Lee, Sang-Min
AU  - Lee SM
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Seoul, Republic of Korea.
FAU - Lee, Chang-Hoon
AU  - Lee CH
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
FAU - Lee, Jinwoo
AU  - Lee J
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Seoul, Republic of Korea.
FAU - Choi, Sun Mi
AU  - Choi SM
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
FAU - Park, Jong Sun
AU  - Park JS
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of 
      Korea.
FAU - Joh, Joon-Sung
AU  - Joh JS
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, National Medical Center, Seoul, Republic of Korea.
FAU - Cho, Young-Jae
AU  - Cho YJ
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of 
      Korea.
FAU - Lee, Yeon Joo
AU  - Lee YJ
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of 
      Korea.
FAU - Kim, Se Joong
AU  - Kim SJ
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of 
      Korea.
FAU - Hwang, Young Ran
AU  - Hwang YR
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of 
      Korea.
FAU - Kim, Hyeonjeong
AU  - Kim H
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
FAU - Ki, Jongeun
AU  - Ki J
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, National Medical Center, Seoul, Republic of Korea.
FAU - Choi, Hyungsook
AU  - Choi H
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of 
      Korea.
FAU - Han, Jiyeon
AU  - Han J
AD  - Medical Research Collaborating Center, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Ahn, Heejung
AU  - Ahn H
AD  - Medical Research Collaborating Center, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Hahn, Seokyung
AU  - Hahn S
AD  - Medical Research Collaborating Center, Seoul National University Hospital, Seoul, 
      Republic of Korea.
FAU - Yim, Jae-Joon
AU  - Yim JJ
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, Seoul National University Hospital, Seoul, Republic of Korea. 
      yimjj@snu.ac.kr.
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Seoul, Republic of Korea. yimjj@snu.ac.kr.
LA  - eng
SI  - ClinicalTrials.gov/NCT01994460
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20170213
PL  - England
TA  - Trials
JT  - Trials
JID - 101263253
RN  - 0 (Antitubercular Agents)
RN  - 8G167061QZ (Ethambutol)
RN  - ISQ9I6J12J (Linezolid)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antitubercular Agents/*administration & dosage/adverse effects
MH  - Clinical Protocols
MH  - *Drug Substitution
MH  - Drug Therapy, Combination
MH  - Ethambutol/*administration & dosage/adverse effects
MH  - Female
MH  - Humans
MH  - Linezolid/*administration & dosage/adverse effects
MH  - Lung/*drug effects/microbiology
MH  - Male
MH  - Middle Aged
MH  - Prospective Studies
MH  - Republic of Korea
MH  - Research Design
MH  - Sputum/microbiology
MH  - Time Factors
MH  - Treatment Outcome
MH  - Tuberculosis, Pulmonary/diagnosis/*drug therapy/microbiology
MH  - Young Adult
PMC - PMC5307889
OTO - NOTNLM
OT  - Ethambutol
OT  - Linezolid
OT  - Multicenter
OT  - Randomized trial
OT  - Tuberculosis
EDAT- 2017/02/15 06:00
MHDA- 2018/02/27 06:00
PMCR- 2017/02/13
CRDT- 2017/02/15 06:00
PHST- 2016/04/16 00:00 [received]
PHST- 2017/01/23 00:00 [accepted]
PHST- 2017/02/15 06:00 [entrez]
PHST- 2017/02/15 06:00 [pubmed]
PHST- 2018/02/27 06:00 [medline]
PHST- 2017/02/13 00:00 [pmc-release]
AID - 10.1186/s13063-017-1811-0 [pii]
AID - 1811 [pii]
AID - 10.1186/s13063-017-1811-0 [doi]
PST - epublish
SO  - Trials. 2017 Feb 13;18(1):68. doi: 10.1186/s13063-017-1811-0.