Pulmonary Tuberculosis Without Resistance to RifampicinPhase 2NCT01994460
Linezolid Instead of Ethambutol in Treatment of Drug-susceptible Tuberculosis
A Phase 2 study testing Linezolid and Ethambutol in people with Pulmonary Tuberculosis Without Resistance to Rifampicin, run by Seoul National University Hospital at 3 sites in South Korea.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Pulmonary Tuberculosis Without Resistance to Rifampicin
- What is being tested?
- Linezolid and Ethambutol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 429 participants
- Where
- 3 sitesSouth Korea
- Study dates
- Jan 2014to Jun 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
3 sites in 1 country.
South Korea3 sites, 3 recruiting
- Recruiting
Seoul National University Bundang Hospital
Seongnam, Kyunggi, 463-707
Jong Sun Park, MD, 031-787-7054, jspark.im@gmail.com
Jong Sun Park, MD
- Recruiting
National Medical Center
Seoul, Seoul, 100-799
Ji Yeon Lee, MD, 82222607284, jedidiah125@gmail.com
Ji Yeon Lee, MD
- Recruiting
SMG-SNU Boramae Medical Center
Seoul, Seoul, 156-707
Deog Kyeom Kim, MD, 02-870-2228, kimdkmd@gmail.com
Deog Kyeom Kim, MD
About this study
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
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).
- Being tested
- Linezolid, Ethambutol
- Keywords
- Tuberculosis
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LinezolidDrug
EthambutolDrug
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: Ethambutol |
| Arm 2 (experimental arm 1) | Experimental | Isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and linezolid (600 mg/day, 2 weeks) Receives: Drug: Linezolid |
| Arm 3 (experimental arm 2) | Experimental | Isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and linezolid (600 mg/day, 4 weeks) Receives: Drug: Linezolid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sputum culture conversion rate on liquid media
Measured: after 2 months of treatment
Secondary outcomes (4)
Sputum culture conversion rate on solid media
Measured: after 2 months of treatment
Time to sputum culture conversion (liquid and solid media)
Measured: During 6 months of treatment
Cure rate
Measured: After 6 months of treatment
Treatment success rate
Measured: after 6 months of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2013 (estimated)
- Study startJan 2014
- Primary completionDec 2015 (estimated)
- Study completionJun 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Tuberculosis Without Resistance to RifampicinStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 429 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health & Welfare, Korea, SMG-SNU Boramae Medical Center, Seoul National University Bundang Hospital, Pfizer
- Responsible party
- Principal investigator, Jae-Joon Yim, Seoul National University Hospital
- Investigators
- Jae-Joon Yim, MD, Principal investigator, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01994460
- Sponsor's protocol ID
- J-1310-026-523
- Status last verified
- Dec 2014
- First submitted
- 13 Nov 2013
- Last updated
- 30 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 30477961Lee 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.
PubMed 28193240
Study at a glance
From the registry record, last updated by the sponsor on 30 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01994460
- Acronym / sponsor ID
- J-1310-026-523
- Keywords
- Tuberculosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 429 participants (estimated)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Collaborators
- Ministry of Health & Welfare, Korea, SMG-SNU Boramae Medical Center, Seoul National University Bundang Hospital, Pfizer
- Study start
- Jan 2014
- Primary completion
- Dec 2015 (estimated)
- Study completion
- Jun 2016 (estimated)
- First posted
- 25 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm 1 (control arm) | Active comparator | Drug: EthambutolStandard treatment for drug-sensitive pulmonary TB using isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and ethambutol (2 months) |
| Arm 2 (experimental arm 1) | Experimental | Drug: LinezolidIsoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and linezolid (600 mg/day, 2 weeks) |
| Arm 3 (experimental arm 2) | Experimental | Drug: LinezolidIsoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and linezolid (600 mg/day, 4 weeks) |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Linezolid | Drug | Arm 2 (experimental arm 1), Arm 3 (experimental arm 2) |
| Ethambutol | Drug | Arm 1 (control arm) |
Primary outcome
Sputum culture conversion rate on liquid media
Time frame: after 2 months of treatment
4 secondary outcomes
Sputum culture conversion rate on solid media
Time frame: after 2 months of treatment
Time to sputum culture conversion (liquid and solid media)
Time frame: During 6 months of treatment
Cure rate
Time frame: After 6 months of treatment
Treatment success rate
Time frame: after 6 months of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Dec 2014.
- Derived from this study: PubMed 30477961Lee 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.
- Derived from this study: PubMed 28193240Lee 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jae-Joon Yim, MD principal investigator
Seoul National University Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Linezolid and Ethambutol in people with Pulmonary Tuberculosis Without Resistance to Rifampicin, run by Seoul National University Hospital at 3 sites in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jae-Joon Yim, MD (82-2-2072-2059, yimjj@snu.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sputum culture conversion rate on liquid media (time frame: after 2 months of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01994460, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2014.