Tuberculosis, Multidrug-ResistantPhase 2MDR-ENDNCT02619994

Treatment Shortening of MDR-TB Using Existing and New Drugs

A Phase 2 study testing Linezolid, Delamanid and Levofloxacin in people with Tuberculosis, Multidrug-Resistant, run by Seoul National University Hospital at 1 site in South Korea.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to compare the efficacy of a 'new treatment regimen including delamanid, linezolid, levofloxacin, and pyrazinamide for nine or twelve months (investigational arm)' and 'the standard treatment regimen including injectables for 20 to 24 months (control arm)' for treating… Read more about this study

Who is it for?: Ages 19 to 85 years
Conditions the study is for: Tuberculosis, Multidrug-Resistant
What is being tested?: Linezolid, Delamanid and Levofloxacin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 214 participants
Where: 1 siteSouth Korea
Study dates: Jan 2016to Jun 2021
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 19 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Males and females aged from 19 to 85 years
Confirmed MDR-TB or RR-TB
On current TB therapy for ≤14 days at the time of enrollment.

Who cannot join

Known any quinolone-resistant MDR-TB
Known XDR-TB
who are pregnant or who are unwilling to use proper contraceptives at childbearing age
Medical history of galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption
The need for ongoing use of prohibited drugs while on study drugs
History of optic neuropathy or peripheral neuropathy
With any of the following test results: i.Absolute neutrophil count < 2000 cells/mL, ii.White blood cell count (WBC) < 3.0 X 103/µL, iii.Hemoglobin < 7.0 g/dL, iv.Serum creatinine > 2.0 mg/dL, v.Aspartate aminotransferase (AST or SGOT) >100 IU/L, vi.Alanine aminotransferase (ALT or SGPT) >100 IU/L, vii.Total bilirubin > 2.0 mg/dL, viii.Albumin < 2.8g/dL, ix.QTcF > 500ms
History of hypersensitivity reaction to the study drugs

Trial locations and contacts

1 site in 1 country.

South Korea1 site

Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine
Seoul, 110-744

Other trials in South Korea

About this study

Official title: Delamanid, Linezolid, Levofloxacin, and Pyrazinamide for the Treatment of Patients With Fluoroquinolone-sensitive MDR-TB: A Phase 2/3, Multicenter, Randomized, Open-label, Clinical Trial

Read the detailed description

This study is a phase II/III, multicenter, randomized, open-label clinical trial of non-inferiority design comparing a new regimen to the World Health Organization-endorsed conventional regimen for fluoroquinolone-sensitive MDR-TB. The control arm uses a conventional treatment regimen with second-line drugs including injectables for 20-24 months. The investigational arm uses a new shorter regimen including delamanid, linezolid, levofloxacin, and pyrazinamide for 9 or 12 months depending on time to sputum culture conversion. The primary outcome is the treatment success rate at 24 months after treatment initiation. Secondary outcomes include time to sputum culture conversion on liquid and solid media, proportions of sputum culture conversion on liquid media after 2 and 6 months of treatment, treatment success rate according to pyrazinamide resistance, and occurrence of adverse events grade 3 and above as evaluated by the Common Terminology Criteria for Adverse Events. The population number is calculated as 102 per group (204 in total).

Conditions: Tuberculosis, Multidrug-Resistant
Being tested: Linezolid, Delamanid, Levofloxacin, Pyrazinamide, Locally-used WHO-approved MDR-TB regimen in Korea
Keywords: Multidrug-resistant tuberculosis, Linezolid, Delamanid, Multicenter randomized trial, Non-inferiority, Shorter regimen
Medical subject headings: Tuberculosis, Multidrug-Resistant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LinezolidDrug
DelamanidDrug
LevofloxacinDrug
PyrazinamideDrug
Locally-used WHO-approved MDR-TB regimen in KoreaDrug

Study groups in NCT02619994
Study group	Role	What they receive
Control Arm	Active comparator	Regimen is the locally-used WHO-approved MDR-TB regimen in Korea based on 2014 Korean guideline of TB management. * Intensive phase regimen consists of four effective second-line anti-TB drugs (including injectables) and pyrazinamide. * Treatment duration: for at least 20 months Receives: Drug: Locally-used WHO-approved MDR-TB regimen in Korea
Experimental Arm	Experimental	Regimen consists of only oral medication using delamanid, linezolid, levofloxacin, and pyrazinamide, for nine or twelve months depending on the time of sputum culture conversion to negative. * Delamanid (100 mg bid for the entire treatment period) * Linezolid (600mg/day for 2 months and 300mg/day afterwards until the end of treatment) * Levofloxacin (750 ~1000 mg/day) * Pyrazinamide (1000~ 2000 mg/day) Receives: Drug: Linezolid; Drug: Delamanid; Drug: Levofloxacin; Drug: Pyrazinamide

What is being measured

The primary outcome is the main question the study is designed to answer.

Treatment Success Rate
To test for non-inferiority of the investigational arm, when the lower limit of the one-sided 97.5% confidence interval of the difference (PT - PC) between investigational and control arms is larger than the non-inferiority margin of - 10%, it will be concluded that the treatment success rate of the investigational arm shows non-inferiority to the treatment success rate of the control arm.
(primary consideration for the modified intention-to-treat results)
Measured: 24 months after treatment start

Secondary outcomes (8)

Time to Sputum Culture Conversion After Treatment Start
To determine whether time to sputum culture conversion after treatment start is statistically different between the control and investigational arms, the median time will be estimated in each group using the Kaplan-Meier method, and the difference in the distribution of time to culture conversion of the two arms will be compared using the log-rank test.
Measured: through study completion (24 months after treatment start)
Sputum Culture Conversion Proportion
Culture conversion rate at month 2 of treatment in participants with positive baseline sputum culture (liquid media).
Measured: At 2 months of treatment
Treatment Success at the End of Treatment
Treatment success rate at the end of treatment.
- control arm (20-24 months)
- experimental arm (40 or 52 weeks)
Measured: At the end of treatment
Proportion of Reverting to Positive Sputum Culture After the End of Treatment
The proportion of patients who experienced a reversion between the end of treatment and up to 24 months after treatment start
Measured: At 24months after treatment start
Treatment Success According to Pyrazinamide Resistance (1)
Treatment success rate of participants with pyrazinamide resistance in the mITT analysis
Measured: At 24months after treatment start
Proportion of Death Between the Control and Investigational Arms
The proportion of participants who died in the control and experimental arm mITT population
Measured: At 24months after treatment start
Sputum Culture Conversion Proportion
Culture conversion rate at month 6 of treatment in participants with positive baseline sputum culture (liquid media).
Measured: At 6 months of treatment start
Treatment Success According to Pyrazinamide Resistance (2)
Treatment success rate of participants without pyrazinamide resistance in the mITT analysis
Measured: At 24 months after treatment start

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2016Jun 2021

First posted2 Dec 2015 (estimated)
Study startJan 2016
Primary completionJun 2021
Study completionJun 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Tuberculosis, Multidrug-ResistantStudies 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: 214 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02619994
Sponsor's protocol ID: MDR-END
Acronym: MDR-END
Status last verified: Nov 2024
First submitted: 24 Nov 2015
Last updated: 3 Jan 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Mok J, Lee M, Kim DK, Kim JS, Jhun BW, Jo KW, Jeon D, Lee T, Lee JY, Park JS, Lee SH, Kang YA, Lee JK, Kwak N, Ahn JH, Shim TS, Kim SY, Kim S, Kim K, Seok KH, Yoon S, Kim YR, Kim J, Yim D, Hahn S, Cho SN, Yim JJ; MDR-END investigators. 9 months of delamanid, linezolid, levofloxacin, and pyrazinamide versus conventional therapy for treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-END): a multicentre, randomised, open-label phase 2/3 non-inferiority trial in South Korea. Lancet. 2022 Oct 29;400(10362):1522-1530. doi: 10.1016/S0140-6736(22)01883-9.
PubMed 36522208
Lee M, Mok J, Kim DK, Shim TS, Koh WJ, Jeon D, Lee T, Lee SH, Kim JS, Park JS, Lee JY, Kim SY, Lee JH, Jo KW, Jhun BW, Kang YA, Ahn JH, Kim CK, Shin S, Song T, Shin SJ, Kim YR, Ahn H, Hahn S, Won HJ, Jang JY, Cho SN, Yim JJ. Delamanid, linezolid, levofloxacin, and pyrazinamide for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (Treatment Shortening of MDR-TB Using Existing and New Drugs, MDR-END): study protocol for a phase II/III, multicenter, randomized, open-label clinical trial. Trials. 2019 Jan 16;20(1):57. doi: 10.1186/s13063-018-3053-1.
PubMed 30651149

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 3 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Delamanid, Linezolid, Levofloxacin, and Pyrazinamide for the Treatment of Patients With Fluoroquinolone-sensitive MDR-TB: A Phase 2/3, Multicenter, Randomized, Open-label, Clinical Trial
ClinicalTrials.gov ID: NCT02619994
Acronym / sponsor ID: MDR-END / MDR-END
Conditions: Tuberculosis, Multidrug-Resistant
Keywords: Multidrug-resistant tuberculosis, Linezolid, Delamanid, Multicenter randomized trial, Non-inferiority, Shorter regimen
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 214 participants (actual)
Lead sponsor: Seoul National University HospitalUniversity, hospital or other
Collaborators: Asan Medical Center, Dankook University, International Tuberculosis Research Center, Pusan National University Yangsan Hospital, Pusan National University Hospital, Samsung Medical Center, Severance Hospital, SMG-SNU Boramae Medical Center, Incheon St.Mary's Hospital, Ulsan University Hospital, Korean Institute of Tuberculosis, National Medical Center, Seoul, Korean Center for Disease Control and Prevention, Korea University Ansan Hospital
Study start: Jan 2016 (actual)
Primary completion: Jun 2021 (actual)
Study completion: Jun 2021 (actual)
First posted: 2 Dec 2015 (estimated)
Results: Posted 3 Jan 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Control Arm	Active comparator	Drug: Locally-used WHO-approved MDR-TB regimen in KoreaRegimen is the locally-used WHO-approved MDR-TB regimen in Korea based on 2014 Korean guideline of TB management. * Intensive phase regimen consists of four effective second-line anti-TB drugs (including injectables) and pyrazinamide. * Treatment duration: for at least 20 months
Experimental Arm	Experimental	Drug: Linezolid, Drug: Delamanid, Drug: Levofloxacin, Drug: PyrazinamideRegimen consists of only oral medication using delamanid, linezolid, levofloxacin, and pyrazinamide, for nine or twelve months depending on the time of sputum culture conversion to negative. * Delamanid (100 mg bid for the entire treatment period) * Linezolid (600mg/day for 2 months and 300mg/day afterwards until the end of treatment) * Levofloxacin (750 ~1000 mg/day) * Pyrazinamide (1000~ 2000 mg/day)

Who may qualify

Ages: 19 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Males and females aged from 19 to 85 years
Confirmed MDR-TB or RR-TB
On current TB therapy for ≤14 days at the time of enrollment.

Key exclusion criteria (8 listed)

Known any quinolone-resistant MDR-TB
Known XDR-TB
who are pregnant or who are unwilling to use proper contraceptives at childbearing age
Medical history of galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption
The need for ongoing use of prohibited drugs while on study drugs

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	Experimental Arm
Delamanid	Drug	Experimental Arm
Levofloxacin	Drug	Experimental Arm
Pyrazinamide	Drug	Experimental Arm
Locally-used WHO-approved MDR-TB regimen in Korea	Drug	Control Arm

Primary outcome

Treatment Success Rate
Time frame: 24 months after treatment start
To test for non-inferiority of the investigational arm, when the lower limit of the one-sided 97.5% confidence interval of the difference (PT - PC) between investigational and control arms is larger than the non-inferiority margin of - 10%, it will be concluded that the treatment success rate of the investigational arm shows non-inferiority to the treatment success rate of the control arm. (primary consideration for the modified intention-to-treat results)

8 secondary outcomes

Time to Sputum Culture Conversion After Treatment Start
Time frame: through study completion (24 months after treatment start)
Sputum Culture Conversion Proportion
Time frame: At 2 months of treatment
Treatment Success at the End of Treatment
Time frame: At the end of treatment
Proportion of Reverting to Positive Sputum Culture After the End of Treatment
Time frame: At 24months after treatment start
Treatment Success According to Pyrazinamide Resistance (1)
Time frame: At 24months after treatment start
Proportion of Death Between the Control and Investigational Arms
Time frame: At 24months after treatment start
Sputum Culture Conversion Proportion
Time frame: At 6 months of treatment start
Treatment Success According to Pyrazinamide Resistance (2)
Time frame: At 24 months after treatment start

Results and safety

Results posted to the registry on 3 Jan 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Control Arm	106	89
Experimental Arm	108	79

Primary outcome: Treatment Success Rate

Time frame: 24 months after treatment start. Count of participants. Unit: Participants

Measure	Control Arm n = 85	Experimental Arm n = 72
Value	60	54

Population analysed: mITT population Participant with \[not assessable\] was not included in the analysis

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: All adverse events and serious adverse events were collected during the entire 24-month study period.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Control Arm	19 of 89 (21.3%)	87 of 89 (97.8%)	2 of 89
Experimental Arm	20 of 79 (25.3%)	78 of 79 (98.7%)	5 of 79

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36522208Mok J, Lee M, Kim DK, Kim JS, Jhun BW, Jo KW, Jeon D, Lee T, Lee JY, Park JS, Lee SH, Kang YA, Lee JK, Kwak N, Ahn JH, Shim TS, Kim SY, Kim S, Kim K, Seok KH, Yoon S, Kim YR, Kim J, Yim D, Hahn S, Cho SN, Yim JJ; MDR-END investigators. 9 months of delamanid, linezolid, levofloxacin, and pyrazinamide versus conventional therapy for treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-END): a multicentre, randomised, open-label phase 2/3 non-inferiority trial in South Korea. Lancet. 2022 Oct 29;400(10362):1522-1530. doi: 10.1016/S0140-6736(22)01883-9.
Derived from this study: PubMed 30651149Lee M, Mok J, Kim DK, Shim TS, Koh WJ, Jeon D, Lee T, Lee SH, Kim JS, Park JS, Lee JY, Kim SY, Lee JH, Jo KW, Jhun BW, Kang YA, Ahn JH, Kim CK, Shin S, Song T, Shin SJ, Kim YR, Ahn H, Hahn S, Won HJ, Jang JY, Cho SN, Yim JJ. Delamanid, linezolid, levofloxacin, and pyrazinamide for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (Treatment Shortening of MDR-TB Using Existing and New Drugs, MDR-END): study protocol for a phase II/III, multicenter, randomized, open-label clinical trial. Trials. 2019 Jan 16;20(1):57. doi: 10.1186/s13063-018-3053-1.

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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.

The record lists no contact. Use the official record to reach the sponsor.

1 site 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, Delamanid and Levofloxacin in people with Tuberculosis, Multidrug-Resistant, run by Seoul National University Hospital at 1 site 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 8 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: finished, as of the sponsor's last update on 3 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Yes. Results are posted in the registry (first posted 3 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Treatment Success Rate (time frame: 24 months after treatment start). 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 NCT02619994, 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 3 Jan 2025.