Therapeutic Drug Monitoring for Linezolid in the Treatment of Rifampin-resistant Tuberculosis
NCT ID: NCT06590428
Last Updated: 2026-01-23
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
RECRUITING
Clinical Phase
NA
Total Enrollment
280 participants
Study Classification
INTERVENTIONAL
Study Start Date
2026-03-31
Study Completion Date
2029-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
This study is a two-arm, pragmatic, open-label, randomized clinical trial to determine the efficacy of Therapeutic Drug Monitoring (TDM) in preventing premature discontinuation of Linezolid (LZD) in participants with Rifampicin-resistant tuberculosis (RR-TB). Following the initiation of treatment, participants will be monitored throughout the approximate 6-month duration of RR-TB therapy.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Linezolid Dosing Strategies in Drug-Resistant TB
NCT05007821
Tuberculosis, Multidrug-Resistant
Tuberculosis
Tuberculosis, Pulmonary
ACTIVE_NOT_RECRUITING
PHASE2
Pharmacokinetic Study of Linezolid for TB Meningitis
NCT03537495
Tuberculosis, Meningeal
Linezolid
COMPLETED
PHASE2
Adjunctive Linezolid for the Treatment of Tuberculous Meningitis
NCT04021121
Tuberculosis, Meningeal
COMPLETED
PHASE2
A Phase 2 Trial to Evaluate the Efficacy and Safety of Linezolid in Tuberculosis Patients. (LIN-CL001)
NCT02279875
Pulmonary Tuberculosis
COMPLETED
PHASE2
An Open-label RCT to Evaluate a New Treatment Regimen for Patients With Multi-drug Resistant Tuberculosis
NCT02454205
Tuberculosis
Multidrug Resistant Tuberculosis
Extensively-drug Resistant Tuberculosis
COMPLETED
PHASE2/PHASE3
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Drug-resistant tuberculosis (TB) is a major global epidemic and poses a particular threat to HIV-infected individuals. With limited effective drugs available for treatment, multidrug-, and extensively drug-resistant TB carry a high mortality rate and threaten global TB and HIV control efforts.
New and repurposed medications have recently been found to improve survival and cure rates. Linezolid-a drug initially developed for the treatment of Gram-positive infections-has considerable anti-TB activity and has been at the center of this treatment revolution. Since 2018, WHO has recommended that all multi DR/rifampicin-resistant (MDR) and extensively drug-resistant tuberculosis (XDR) tuberculosis treatment regimens include linezolid. When given long-term, however, linezolid-associated toxicity-particularly myelosuppression and peripheral neuropathy-is very common, affecting 50-80% of patients and often requiring a temporary or permanent discontinuation of therapy. Such interruptions put patients at risk of treatment failure and the emergence of additional resistance to linezolid or one of the other drugs in the regimen. As linezolid use continues to increase worldwide, such resistance could become widespread, squandering a valuable medication. Previously conducted research has shown that linezolid toxicities are associated with trough plasma concentration and that the drug has considerable inter-individual variability. The investigator team, therefore, hypothesize that therapeutic drug monitoring (TDM) could identify those with higher linezolid concentrations and permit pre-emptive dose reductions that could avert drug toxicity and premature discontinuation.
This study will take place at the Nkqubela TB Specialist Hospital in East London, South Africa. TB diagnosis and initial treatment regimen will be determined by the hospital clinical team, per local guidelines. Following enrollment, participants will be randomized after enrollment to either undergo a therapeutic drug monitoring (TDM) strategy for LZD, or standard of care (SOC). Participants in both arms will have a trough plasma linezolid concentration drawn approximately one week after enrollment (within one month of TB treatment initiation). The PK specimens collected from TDM arm participants will be analyzed by University of Cape Town lab staff. The PK specimens collected from SOC participants will be stored for future analysis.
Standard treatment for RR-TB in South Africa includes 6 months of therapy, including linezolid 600 mg daily for duration of treatment. Those in the TDM arm whose concentration is above a set threshold (2.5 mg/L) will have their LZD dose reduced to 300mg daily, while those in the SOC arm will receive routine monitoring alone. All participants will be screened monthly for hematologic and neurologic toxicity. Hospital and clinic providers will manage all treatment other than the TDM-guided linezolid dose reduction. If participants in either the SOC or TDM arm experience linezolid toxicity, hospital and clinic providers may choose to temporarily or permanently discontinue linezolid, regardless of any prior TDM-guided dose reduction, in accordance with South African national guidelines.
Aim 1 (Primary Outcome Measure of this study) and Aim 2 (the first Secondary Outcome Measure) are described in the Outcome Measures section. For Aim 3, population PK modeling will be used to explore the complex relationship between linezolid pharmacokinetic parameters and the trajectory of toxicities over time. It will also be determined as to whether those whose dose is lowered still meet exposure targets for drug efficacy. South Africa has among the highest global burden of drug-resistant TB and HIV and has led the world in the rollout of new RR-TB drugs and regimens. The aims of this study will answer fundamental questions about LZD pharmacology that will directly inform its use in South Africa and worldwide.
New and repurposed medications have recently been found to improve survival and cure rates. Linezolid-a drug initially developed for the treatment of Gram-positive infections-has considerable anti-TB activity and has been at the center of this treatment revolution. Since 2018, WHO has recommended that all multi DR/rifampicin-resistant (MDR) and extensively drug-resistant tuberculosis (XDR) tuberculosis treatment regimens include linezolid. When given long-term, however, linezolid-associated toxicity-particularly myelosuppression and peripheral neuropathy-is very common, affecting 50-80% of patients and often requiring a temporary or permanent discontinuation of therapy. Such interruptions put patients at risk of treatment failure and the emergence of additional resistance to linezolid or one of the other drugs in the regimen. As linezolid use continues to increase worldwide, such resistance could become widespread, squandering a valuable medication. Previously conducted research has shown that linezolid toxicities are associated with trough plasma concentration and that the drug has considerable inter-individual variability. The investigator team, therefore, hypothesize that therapeutic drug monitoring (TDM) could identify those with higher linezolid concentrations and permit pre-emptive dose reductions that could avert drug toxicity and premature discontinuation.
This study will take place at the Nkqubela TB Specialist Hospital in East London, South Africa. TB diagnosis and initial treatment regimen will be determined by the hospital clinical team, per local guidelines. Following enrollment, participants will be randomized after enrollment to either undergo a therapeutic drug monitoring (TDM) strategy for LZD, or standard of care (SOC). Participants in both arms will have a trough plasma linezolid concentration drawn approximately one week after enrollment (within one month of TB treatment initiation). The PK specimens collected from TDM arm participants will be analyzed by University of Cape Town lab staff. The PK specimens collected from SOC participants will be stored for future analysis.
Standard treatment for RR-TB in South Africa includes 6 months of therapy, including linezolid 600 mg daily for duration of treatment. Those in the TDM arm whose concentration is above a set threshold (2.5 mg/L) will have their LZD dose reduced to 300mg daily, while those in the SOC arm will receive routine monitoring alone. All participants will be screened monthly for hematologic and neurologic toxicity. Hospital and clinic providers will manage all treatment other than the TDM-guided linezolid dose reduction. If participants in either the SOC or TDM arm experience linezolid toxicity, hospital and clinic providers may choose to temporarily or permanently discontinue linezolid, regardless of any prior TDM-guided dose reduction, in accordance with South African national guidelines.
Aim 1 (Primary Outcome Measure of this study) and Aim 2 (the first Secondary Outcome Measure) are described in the Outcome Measures section. For Aim 3, population PK modeling will be used to explore the complex relationship between linezolid pharmacokinetic parameters and the trajectory of toxicities over time. It will also be determined as to whether those whose dose is lowered still meet exposure targets for drug efficacy. South Africa has among the highest global burden of drug-resistant TB and HIV and has led the world in the rollout of new RR-TB drugs and regimens. The aims of this study will answer fundamental questions about LZD pharmacology that will directly inform its use in South Africa and worldwide.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Rifampin-resistant Tuberculosis
Drug-resistant Tuberculosis
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
1:1 randomization.
Participants will receive 600mg daily dose of oral LZD for Rifampicin-resistant tuberculosis (RR-TB) as part of standard of care for both arms. This dosage may be reduced to 300mg daily based on the plasma trough concentration obtained from the first pharmacokinetic (PK) specimen.
Participants will receive 600mg daily dose of oral LZD for Rifampicin-resistant tuberculosis (RR-TB) as part of standard of care for both arms. This dosage may be reduced to 300mg daily based on the plasma trough concentration obtained from the first pharmacokinetic (PK) specimen.
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Therapeutic Drug Monitoring (TDM)
Participants in the TDM arm will have their linezolid dose reduced if their trough concentration is greater than 2.5 mg/L
Group Type
OTHER
Therapeutic Drug Monitoring for Linezolid
Intervention Type
OTHER
TDM with dose adjustment for trough concentration \>2.5 mg/L LZD
Standard of Care (SOC)
Participants in the SOC arm will have their linezolid adjusted or held if they develop clinical adverse events.
Group Type
NO_INTERVENTION
No interventions assigned to this group
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Therapeutic Drug Monitoring for Linezolid
TDM with dose adjustment for trough concentration \>2.5 mg/L LZD
Intervention Type
OTHER
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Adult male or female patient \> 18 years of age
* Microbiological confirmation of rifampicin-resistant tuberculosis (e.g., phenotypic drug susceptibility testing, GeneXpert MTB/RIF™). Participants may have resistance to additional medications as well - i.e., MDR and XDR TB - but must have resistance to at least rifampin
* Initiated on a RR-TB treatment regimen containing linezolid, no more than 14 days prior to enrollment
* HIV status is known
* Both HIV-positive and HIV-negative individuals are eligible
* If an individual reports unknown HIV results, they must consent to HIV testing at time of enrollment to confirm status. If they decline to be tested, they are not eligible for the study
* If an individual declines to share his or her HIV status, they are not eligible for the study. Patients reporting unknown HIV status will be required to have had confirmatory testing within 6 months of study screening
* Microbiological confirmation of rifampicin-resistant tuberculosis (e.g., phenotypic drug susceptibility testing, GeneXpert MTB/RIF™). Participants may have resistance to additional medications as well - i.e., MDR and XDR TB - but must have resistance to at least rifampin
* Initiated on a RR-TB treatment regimen containing linezolid, no more than 14 days prior to enrollment
* HIV status is known
* Both HIV-positive and HIV-negative individuals are eligible
* If an individual reports unknown HIV results, they must consent to HIV testing at time of enrollment to confirm status. If they decline to be tested, they are not eligible for the study
* If an individual declines to share his or her HIV status, they are not eligible for the study. Patients reporting unknown HIV status will be required to have had confirmatory testing within 6 months of study screening
Exclusion Criteria
* Current unstable or uncontrolled major medical comorbidity that would interfere with subject's ability to participate in the study
* Pregnant at time of screening
* Initial linezolid dose \< 600mg daily
* Pregnant at time of screening
* Initial linezolid dose \< 600mg daily
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University of Cape Town
OTHER
Sponsor Role
collaborator
St George's, University of London
OTHER
Sponsor Role
collaborator
Emory University
OTHER
Sponsor Role
collaborator
National Department of Health, South Africa
UNKNOWN
Sponsor Role
collaborator
Columbia University
OTHER
Sponsor Role
collaborator
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Sponsor Role
collaborator
Albert Einstein College of Medicine
OTHER
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Responsibility Role
SPONSOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
James CM Brust, MD
Role: PRINCIPAL_INVESTIGATOR
Albert Einstein College of Medicine
Gary Maartens, MBChB
Role: PRINCIPAL_INVESTIGATOR
University of Cape Town
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Nkqubela TB Specialist Hospital
East London, Eastern Cape, South Africa
Site Status
RECRUITING
Countries
Review the countries where the study has at least one active or historical site.
South Africa
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Gary Maartens, MBChB
Role: primary
References
Explore related publications, articles, or registry entries linked to this study.
McArthur JH. The reliability and validity of the subjective peripheral neuropathy screen. J Assoc Nurses AIDS Care. 1998 Jul-Aug;9(4):84-94. doi: 10.1016/S1055-3290(98)80048-4.
Reference Type
BACKGROUND
Cherry CL, Wesselingh SL, Lal L, McArthur JC. Evaluation of a clinical screening tool for HIV-associated sensory neuropathies. Neurology. 2005 Dec 13;65(11):1778-81. doi: 10.1212/01.wnl.0000187119.33075.41.
Reference Type
BACKGROUND
Rusch-Gerdes S, Pfyffer GE, Casal M, Chadwick M, Siddiqi S. Multicenter laboratory validation of the BACTEC MGIT 960 technique for testing susceptibilities of Mycobacterium tuberculosis to classical second-line drugs and newer antimicrobials. J Clin Microbiol. 2006 Mar;44(3):688-92. doi: 10.1128/JCM.44.3.688-692.2006.
Reference Type
BACKGROUND
World Health Organization. Definitions and reporting framework for tuberculosis - 2013 revision (updated December 2014 and January 2020). WHO/HTM/TB/20132 Geneva.
Reference Type
BACKGROUND
Boak LM, Rayner CR, Grayson ML, Paterson DL, Spelman D, Khumra S, Capitano B, Forrest A, Li J, Nation RL, Bulitta JB. Clinical population pharmacokinetics and toxicodynamics of linezolid. Antimicrob Agents Chemother. 2014;58(4):2334-43. doi: 10.1128/AAC.01885-13. Epub 2014 Feb 10.
Reference Type
BACKGROUND
Friberg LE, Henningsson A, Maas H, Nguyen L, Karlsson MO. Model of chemotherapy-induced myelosuppression with parameter consistency across drugs. J Clin Oncol. 2002 Dec 15;20(24):4713-21. doi: 10.1200/JCO.2002.02.140.
Reference Type
BACKGROUND
Sharma A, Jusko WJ. Characteristics of indirect pharmacodynamic models and applications to clinical drug responses. Br J Clin Pharmacol. 1998 Mar;45(3):229-39. doi: 10.1046/j.1365-2125.1998.00676.x.
Reference Type
BACKGROUND
Abdelwahab MT, Wasserman S, Brust JCM, Dheda K, Wiesner L, Gandhi NR, Warren RM, Sirgel FA, Meintjes G, Maartens G, Denti P. Linezolid Population Pharmacokinetics in South African Adults with Drug-Resistant Tuberculosis. Antimicrob Agents Chemother. 2021 Nov 17;65(12):e0138121. doi: 10.1128/AAC.01381-21. Epub 2021 Sep 20.
Reference Type
BACKGROUND
Bigelow KM, Deitchman AN, Li SY, Barnes-Boyle K, Tyagi S, Soni H, Dooley KE, Savic RM, Nuermberger EL. Pharmacodynamic Correlates of Linezolid Activity and Toxicity in Murine Models of Tuberculosis. J Infect Dis. 2021 Jun 4;223(11):1855-1864. doi: 10.1093/infdis/jiaa016.
Reference Type
BACKGROUND
Stalker DJ, Jungbluth GL. Clinical pharmacokinetics of linezolid, a novel oxazolidinone antibacterial. Clin Pharmacokinet. 2003;42(13):1129-40. doi: 10.2165/00003088-200342130-00004.
Reference Type
BACKGROUND
Svensson EM, Aweeka F, Park JG, Marzan F, Dooley KE, Karlsson MO. Model-based estimates of the effects of efavirenz on bedaquiline pharmacokinetics and suggested dose adjustments for patients coinfected with HIV and tuberculosis. Antimicrob Agents Chemother. 2013 Jun;57(6):2780-7. doi: 10.1128/AAC.00191-13. Epub 2013 Apr 9.
Reference Type
BACKGROUND
Falzon D, Gandhi N, Migliori GB, Sotgiu G, Cox HS, Holtz TH, Hollm-Delgado MG, Keshavjee S, DeRiemer K, Centis R, D'Ambrosio L, Lange CG, Bauer M, Menzies D; Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB. Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes. Eur Respir J. 2013 Jul;42(1):156-68. doi: 10.1183/09031936.00134712. Epub 2012 Oct 25.
Reference Type
BACKGROUND
World Health Organization. Global Tuberculosis Report 2022. Geneva.
Reference Type
BACKGROUND
Shah NS, Wright A, Bai GH, Barrera L, Boulahbal F, Martin-Casabona N, Drobniewski F, Gilpin C, Havelkova M, Lepe R, Lumb R, Metchock B, Portaels F, Rodrigues MF, Rusch-Gerdes S, Van Deun A, Vincent V, Laserson K, Wells C, Cegielski JP. Worldwide emergence of extensively drug-resistant tuberculosis. Emerg Infect Dis. 2007 Mar;13(3):380-7. doi: 10.3201/eid1303.061400.
Reference Type
BACKGROUND
Migliori GB, Sotgiu G, Gandhi NR, Falzon D, DeRiemer K, Centis R, Hollm-Delgado MG, Palmero D, Perez-Guzman C, Vargas MH, D'Ambrosio L, Spanevello A, Bauer M, Chan ED, Schaaf HS, Keshavjee S, Holtz TH, Menzies D; "The Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB". Drug resistance beyond extensively drug-resistant tuberculosis: individual patient data meta-analysis. Eur Respir J. 2013 Jul;42(1):169-179. doi: 10.1183/09031936.00136312. Epub 2012 Oct 11.
Reference Type
BACKGROUND
Centers for Disease Control and Prevention (CDC). Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs--worldwide, 2000-2004. MMWR Morb Mortal Wkly Rep. 2006 Mar 24;55(11):301-5.
Reference Type
BACKGROUND
Gandhi NR, Shah NS, Andrews JR, Vella V, Moll AP, Scott M, Weissman D, Marra C, Lalloo UG, Friedland GH; Tugela Ferry Care and Research (TF CARES) Collaboration. HIV coinfection in multidrug- and extensively drug-resistant tuberculosis results in high early mortality. Am J Respir Crit Care Med. 2010 Jan 1;181(1):80-6. doi: 10.1164/rccm.200907-0989OC. Epub 2009 Oct 15.
Reference Type
BACKGROUND
Migliori GB, Besozzi G, Girardi E, Kliiman K, Lange C, Toungoussova OS, Ferrara G, Cirillo DM, Gori A, Matteelli A, Spanevello A, Codecasa LR, Raviglione MC; SMIRA/TBNET Study Group. Clinical and operational value of the extensively drug-resistant tuberculosis definition. Eur Respir J. 2007 Oct;30(4):623-6. doi: 10.1183/09031936.00077307. Epub 2007 Aug 9.
Reference Type
BACKGROUND
Shah NS, Pratt R, Armstrong L, Robison V, Castro KG, Cegielski JP. Extensively drug-resistant tuberculosis in the United States, 1993-2007. JAMA. 2008 Nov 12;300(18):2153-60. doi: 10.1001/jama.300.18.2153.
Reference Type
BACKGROUND
Gandhi NR, Moll A, Sturm AW, Pawinski R, Govender T, Lalloo U, Zeller K, Andrews J, Friedland G. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006 Nov 4;368(9547):1575-80. doi: 10.1016/S0140-6736(06)69573-1.
Reference Type
BACKGROUND
Pietersen E, Ignatius E, Streicher EM, Mastrapa B, Padanilam X, Pooran A, Badri M, Lesosky M, van Helden P, Sirgel FA, Warren R, Dheda K. Long-term outcomes of patients with extensively drug-resistant tuberculosis in South Africa: a cohort study. Lancet. 2014 Apr 5;383(9924):1230-9. doi: 10.1016/S0140-6736(13)62675-6. Epub 2014 Jan 17.
Reference Type
BACKGROUND
Schnippel K, Ndjeka N, Maartens G, Meintjes G, Master I, Ismail N, Hughes J, Ferreira H, Padanilam X, Romero R, Te Riele J, Conradie F. Effect of bedaquiline on mortality in South African patients with drug-resistant tuberculosis: a retrospective cohort study. Lancet Respir Med. 2018 Sep;6(9):699-706. doi: 10.1016/S2213-2600(18)30235-2. Epub 2018 Jul 11.
Reference Type
BACKGROUND
Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB treatment-2017; Ahmad N, Ahuja SD, Akkerman OW, Alffenaar JC, Anderson LF, Baghaei P, Bang D, Barry PM, Bastos ML, Behera D, Benedetti A, Bisson GP, Boeree MJ, Bonnet M, Brode SK, Brust JCM, Cai Y, Caumes E, Cegielski JP, Centis R, Chan PC, Chan ED, Chang KC, Charles M, Cirule A, Dalcolmo MP, D'Ambrosio L, de Vries G, Dheda K, Esmail A, Flood J, Fox GJ, Frechet-Jachym M, Fregona G, Gayoso R, Gegia M, Gler MT, Gu S, Guglielmetti L, Holtz TH, Hughes J, Isaakidis P, Jarlsberg L, Kempker RR, Keshavjee S, Khan FA, Kipiani M, Koenig SP, Koh WJ, Kritski A, Kuksa L, Kvasnovsky CL, Kwak N, Lan Z, Lange C, Laniado-Laborin R, Lee M, Leimane V, Leung CC, Leung EC, Li PZ, Lowenthal P, Maciel EL, Marks SM, Mase S, Mbuagbaw L, Migliori GB, Milanov V, Miller AC, Mitnick CD, Modongo C, Mohr E, Monedero I, Nahid P, Ndjeka N, O'Donnell MR, Padayatchi N, Palmero D, Pape JW, Podewils LJ, Reynolds I, Riekstina V, Robert J, Rodriguez M, Seaworth B, Seung KJ, Schnippel K, Shim TS, Singla R, Smith SE, Sotgiu G, Sukhbaatar G, Tabarsi P, Tiberi S, Trajman A, Trieu L, Udwadia ZF, van der Werf TS, Veziris N, Viiklepp P, Vilbrun SC, Walsh K, Westenhouse J, Yew WW, Yim JJ, Zetola NM, Zignol M, Menzies D. Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis. Lancet. 2018 Sep 8;392(10150):821-834. doi: 10.1016/S0140-6736(18)31644-1.
Reference Type
BACKGROUND
Conradie F, Diacon A, Howell P, et al. Sustained high rate of successful treatment outcomes: Interim results of 75 patients in the Nix-TB clinical study of pretomanid, bedaquiline and linezolid. 49th Union World Conference on Lung Health The Hague, Netherlands 24-27 October 2018 Abstract OA03-213-25.
Reference Type
BACKGROUND
Diacon AH, De Jager VR, Dawson R, Narunsky K, Vanker N, Burger DA, Everitt D, Pappas F, Nedelman J, Mendel CM. Fourteen-Day Bactericidal Activity, Safety, and Pharmacokinetics of Linezolid in Adults with Drug-Sensitive Pulmonary Tuberculosis. Antimicrob Agents Chemother. 2020 Mar 24;64(4):e02012-19. doi: 10.1128/AAC.02012-19. Print 2020 Mar 24.
Reference Type
BACKGROUND
Zurenko GE, Yagi BH, Schaadt RD, Allison JW, Kilburn JO, Glickman SE, Hutchinson DK, Barbachyn MR, Brickner SJ. In vitro activities of U-100592 and U-100766, novel oxazolidinone antibacterial agents. Antimicrob Agents Chemother. 1996 Apr;40(4):839-45. doi: 10.1128/AAC.40.4.839.
Reference Type
BACKGROUND
Cynamon MH, Klemens SP, Sharpe CA, Chase S. Activities of several novel oxazolidinones against Mycobacterium tuberculosis in a murine model. Antimicrob Agents Chemother. 1999 May;43(5):1189-91. doi: 10.1128/AAC.43.5.1189.
Reference Type
BACKGROUND
Lee M, Lee J, Carroll MW, Choi H, Min S, Song T, Via LE, Goldfeder LC, Kang E, Jin B, Park H, Kwak H, Kim H, Jeon HS, Jeong I, Joh JS, Chen RY, Olivier KN, Shaw PA, Follmann D, Song SD, Lee JK, Lee D, Kim CT, Dartois V, Park SK, Cho SN, Barry CE 3rd. Linezolid for treatment of chronic extensively drug-resistant tuberculosis. N Engl J Med. 2012 Oct 18;367(16):1508-18. doi: 10.1056/NEJMoa1201964.
Reference Type
BACKGROUND
Conradie F, Diacon AH, Ngubane N, Howell P, Everitt D, Crook AM, Mendel CM, Egizi E, Moreira J, Timm J, McHugh TD, Wills GH, Bateson A, Hunt R, Van Niekerk C, Li M, Olugbosi M, Spigelman M; Nix-TB Trial Team. Treatment of Highly Drug-Resistant Pulmonary Tuberculosis. N Engl J Med. 2020 Mar 5;382(10):893-902. doi: 10.1056/NEJMoa1901814.
Reference Type
BACKGROUND
Conradie F, Bagdasaryan TR, Borisov S, Howell P, Mikiashvili L, Ngubane N, Samoilova A, Skornykova S, Tudor E, Variava E, Yablonskiy P, Everitt D, Wills GH, Sun E, Olugbosi M, Egizi E, Li M, Holsta A, Timm J, Bateson A, Crook AM, Fabiane SM, Hunt R, McHugh TD, Tweed CD, Foraida S, Mendel CM, Spigelman M; ZeNix Trial Team. Bedaquiline-Pretomanid-Linezolid Regimens for Drug-Resistant Tuberculosis. N Engl J Med. 2022 Sep 1;387(9):810-823. doi: 10.1056/NEJMoa2119430.
Reference Type
BACKGROUND
Nyang'wa BT, Berry C, Kazounis E, Motta I, Parpieva N, Tigay Z, Solodovnikova V, Liverko I, Moodliar R, Dodd M, Ngubane N, Rassool M, McHugh TD, Spigelman M, Moore DAJ, Ritmeijer K, du Cros P, Fielding K; TB-PRACTECAL Study Collaborators. A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis. N Engl J Med. 2022 Dec 22;387(25):2331-2343. doi: 10.1056/NEJMoa2117166.
Reference Type
BACKGROUND
World Health Organization. Treatment guidelines for multidrug- and rifampicin-resistant tuberculosis: 2018 update; Pre-final text; WHO/CDS/TB/2018.15 Geneva.
Reference Type
BACKGROUND
Department of Health South Africa. Clinical Management of Rifampin-Resistant Tuberculosis: Updated Clinical Reference Guide. 2023.
Reference Type
BACKGROUND
WHO consolidated guidelines on tuberculosis: Module 4: Treatment - Drug-resistant tuberculosis treatment [Internet]. Geneva: World Health Organization; 2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK558570/
Reference Type
BACKGROUND
World Health Organization. The END TB Strategy. WHO/HTM/TB/201519; Geneva, Switzerland 2015.
Reference Type
BACKGROUND
Fauci AS, Eisinger RW. Reimagining the Research Approach to Tuberculosisdagger. Am J Trop Med Hyg. 2018 Mar;98(3):650-652. doi: 10.4269/ajtmh.17-0999. Epub 2018 Jan 11.
Reference Type
BACKGROUND
De Vriese AS, Coster RV, Smet J, Seneca S, Lovering A, Van Haute LL, Vanopdenbosch LJ, Martin JJ, Groote CC, Vandecasteele S, Boelaert JR. Linezolid-induced inhibition of mitochondrial protein synthesis. Clin Infect Dis. 2006 Apr 15;42(8):1111-7. doi: 10.1086/501356. Epub 2006 Mar 13.
Reference Type
BACKGROUND
Zyvox [package insert]; https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/021130s032,021131s026,021132s031lbl.pdf (accessed Sep 10, 2023).
Reference Type
BACKGROUND
Sotgiu G, Centis R, D'Ambrosio L, Alffenaar JW, Anger HA, Caminero JA, Castiglia P, De Lorenzo S, Ferrara G, Koh WJ, Schecter GF, Shim TS, Singla R, Skrahina A, Spanevello A, Udwadia ZF, Villar M, Zampogna E, Zellweger JP, Zumla A, Migliori GB. Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: systematic review and meta-analysis. Eur Respir J. 2012 Dec;40(6):1430-42. doi: 10.1183/09031936.00022912. Epub 2012 Apr 10.
Reference Type
BACKGROUND
Cox H, Ford N. Linezolid for the treatment of complicated drug-resistant tuberculosis: a systematic review and meta-analysis. Int J Tuberc Lung Dis. 2012 Apr;16(4):447-54. doi: 10.5588/ijtld.11.0451.
Reference Type
BACKGROUND
Zhang X, Falagas ME, Vardakas KZ, Wang R, Qin R, Wang J, Liu Y. Systematic review and meta-analysis of the efficacy and safety of therapy with linezolid containing regimens in the treatment of multidrug-resistant and extensively drug-resistant tuberculosis. J Thorac Dis. 2015 Apr;7(4):603-15. doi: 10.3978/j.issn.2072-1439.2015.03.10.
Reference Type
BACKGROUND
Kwon YS, Jang JG, Lee J, Choi KJ, Park JE. Risk factors for peripheral neuropathy in patients on linezolid-containing regimens for drug-resistant TB. Int J Tuberc Lung Dis. 2023 Mar 1;27(3):232-234. doi: 10.5588/ijtld.22.0423. No abstract available.
Reference Type
BACKGROUND
Padmapriyadarsini C, Solanki R, Jeyakumar SM, Bhatnagar A, Muthuvijaylaksmi M, Jeyadeepa B, Reddy D, Shah P, Sridhar R, Vohra V, Bhui NK. Linezolid Pharmacokinetics and Its Association with Adverse Drug Reactions in Patients with Drug-Resistant Pulmonary Tuberculosis. Antibiotics (Basel). 2023 Apr 6;12(4):714. doi: 10.3390/antibiotics12040714.
Reference Type
BACKGROUND
Wasserman S, Meintjes G, Maartens G. Linezolid in the treatment of drug-resistant tuberculosis: the challenge of its narrow therapeutic index. Expert Rev Anti Infect Ther. 2016 Oct;14(10):901-15. doi: 10.1080/14787210.2016.1225498. Epub 2016 Aug 27.
Reference Type
BACKGROUND
Cattaneo D, Marriott DJ, Gervasoni C. Hematological toxicities associated with linezolid therapy in adults: key findings and clinical considerations. Expert Rev Clin Pharmacol. 2023 Mar;16(3):219-230. doi: 10.1080/17512433.2023.2181160. Epub 2023 Feb 21.
Reference Type
BACKGROUND
Cattaneo D, Baldelli S, Cerea M, Landonio S, Meraviglia P, Simioni E, Cozzi V, Fucile S, Gazzaniga A, Clementi E, Galli M, Rizzardini G, Gervasoni C. Comparison of the in vivo pharmacokinetics and in vitro dissolution of raltegravir in HIV patients receiving the drug by swallowing or by chewing. Antimicrob Agents Chemother. 2012 Dec;56(12):6132-6. doi: 10.1128/AAC.00942-12. Epub 2012 Sep 10.
Reference Type
BACKGROUND
Zhang H, He Y, Davies Forsman L, Paues J, Werngren J, Niward K, Schon T, Bruchfeld J, Alffenaar JW, Hu Y. Population pharmacokinetics and dose evaluations of linezolid in the treatment of multidrug-resistant tuberculosis. Front Pharmacol. 2023 Jan 9;13:1032674. doi: 10.3389/fphar.2022.1032674. eCollection 2022.
Reference Type
BACKGROUND
Alghamdi WA, Al-Shaer MH, An G, Alsultan A, Kipiani M, Barbakadze K, Mikiashvili L, Ashkin D, Griffith DE, Cegielski JP, Kempker RR, Peloquin CA. Population Pharmacokinetics of Linezolid in Tuberculosis Patients: Dosing Regimen Simulation and Target Attainment Analysis. Antimicrob Agents Chemother. 2020 Sep 21;64(10):e01174-20. doi: 10.1128/AAC.01174-20. Print 2020 Sep 21.
Reference Type
BACKGROUND
Millard J, Pertinez H, Bonnett L, Hodel EM, Dartois V, Johnson JL, Caws M, Tiberi S, Bolhuis M, Alffenaar JC, Davies G, Sloan DJ. Linezolid pharmacokinetics in MDR-TB: a systematic review, meta-analysis and Monte Carlo simulation. J Antimicrob Chemother. 2018 Jul 1;73(7):1755-1762. doi: 10.1093/jac/dky096.
Reference Type
BACKGROUND
Wasserman S, Brust JCM, Abdelwahab MT, Little F, Denti P, Wiesner L, Gandhi NR, Meintjes G, Maartens G. Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study. J Antimicrob Chemother. 2022 Mar 31;77(4):1146-1154. doi: 10.1093/jac/dkac019.
Reference Type
BACKGROUND
Song T, Lee M, Jeon HS, Park Y, Dodd LE, Dartois V, Follman D, Wang J, Cai Y, Goldfeder LC, Olivier KN, Xie Y, Via LE, Cho SN, Barry CE 3rd, Chen RY. Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis. EBioMedicine. 2015 Oct 9;2(11):1627-33. doi: 10.1016/j.ebiom.2015.09.051. eCollection 2015 Nov.
Reference Type
BACKGROUND
Wasserman S, Denti P, Brust JCM, Abdelwahab M, Hlungulu S, Wiesner L, Norman J, Sirgel FA, Warren RM, Esmail A, Dheda K, Gandhi NR, Meintjes G, Maartens G. Linezolid Pharmacokinetics in South African Patients with Drug-Resistant Tuberculosis and a High Prevalence of HIV Coinfection. Antimicrob Agents Chemother. 2019 Feb 26;63(3):e02164-18. doi: 10.1128/AAC.02164-18. Print 2019 Mar.
Reference Type
BACKGROUND
Srivastava S, Magombedze G, Koeuth T, Sherman C, Pasipanodya JG, Raj P, Wakeland E, Deshpande D, Gumbo T. Linezolid Dose That Maximizes Sterilizing Effect While Minimizing Toxicity and Resistance Emergence for Tuberculosis. Antimicrob Agents Chemother. 2017 Jul 25;61(8):e00751-17. doi: 10.1128/AAC.00751-17. Print 2017 Aug.
Reference Type
BACKGROUND
Kamp J, Bolhuis MS, Tiberi S, Akkerman OW, Centis R, de Lange WC, Kosterink JG, van der Werf TS, Migliori GB, Alffenaar JC. Simple strategy to assess linezolid exposure in patients with multi-drug-resistant and extensively-drug-resistant tuberculosis. Int J Antimicrob Agents. 2017 Jun;49(6):688-694. doi: 10.1016/j.ijantimicag.2017.01.017. Epub 2017 Apr 4.
Reference Type
BACKGROUND
Rao GG, Konicki R, Cattaneo D, Alffenaar JW, Marriott DJE, Neely M; IATDMCT Antimicrobial Scientific Committee. Therapeutic Drug Monitoring Can Improve Linezolid Dosing Regimens in Current Clinical Practice: A Review of Linezolid Pharmacokinetics and Pharmacodynamics. Ther Drug Monit. 2020 Feb;42(1):83-92. doi: 10.1097/FTD.0000000000000710.
Reference Type
BACKGROUND
Zhou W, Nie W, Wang Q, Shi W, Yang Y, Li Q, Zhu H, Liu Z, Ding Y, Lu Y, Chu N. Linezolid Pharmacokinetics/Pharmacodynamics-Based Optimal Dosing for Multidrug-Resistant Tuberculosis. Int J Antimicrob Agents. 2022 Jun;59(6):106589. doi: 10.1016/j.ijantimicag.2022.106589. Epub 2022 Apr 9.
Reference Type
BACKGROUND
Cattaneo D, Orlando G, Cozzi V, Cordier L, Baldelli S, Merli S, Fucile S, Gulisano C, Rizzardini G, Clementi E. Linezolid plasma concentrations and occurrence of drug-related haematological toxicity in patients with gram-positive infections. Int J Antimicrob Agents. 2013 Jun;41(6):586-9. doi: 10.1016/j.ijantimicag.2013.02.020. Epub 2013 Apr 4.
Reference Type
BACKGROUND
Eimer J, Frechet-Jachym M, Le Du D, Caumes E, El-Helali N, Marigot-Outtandy D, Mechai F, Peytavin G, Pourcher V, Rioux C, Yazdanpanah Y, Robert J, Guglielmetti L; LZDM group. Association Between Increased Linezolid Plasma Concentrations and the Development of Severe Toxicity in Multidrug-Resistant Tuberculosis Treatment. Clin Infect Dis. 2023 Feb 8;76(3):e947-e956. doi: 10.1093/cid/ciac485.
Reference Type
BACKGROUND
Mase A, Lowenthal P, True L, Henry L, Barry P, Flood J. Low-Dose Linezolid for Treatment of Patients With Multidrug-Resistant Tuberculosis. Open Forum Infect Dis. 2022 Oct 5;9(12):ofac500. doi: 10.1093/ofid/ofac500. eCollection 2022 Dec.
Reference Type
BACKGROUND
Begg EJ, Barclay ML, Kirkpatrick CJ. The therapeutic monitoring of antimicrobial agents. Br J Clin Pharmacol. 1999 Jan;47(1):23-30. doi: 10.1046/j.1365-2125.1999.00850.x.
Reference Type
BACKGROUND
Haley CA, Schechter MC, Ashkin D, Peloquin CA, Peter Cegielski J, Andrino BB, Burgos M, Caloia LA, Chen L, Colon-Semidey A, DeSilva MB, Dhanireddy S, Dorman SE, Dworkin FF, Hammond-Epstein H, Easton AV, Gaensbauer JT, Ghassemieh B, Gomez ME, Horne D, Jasuja S, Jones BA, Kaplan LJ, Khan AE, Kracen E, Labuda S, Landers KM, Lardizabal AA, Lasley MT, Letzer DM, Lopes VK, Lubelchek RJ, Patricia Macias C, Mihalyov A, Misch EA, Murray JA, Narita M, Nilsen DM, Ninneman MJ, Ogawa L, Oladele A, Overman M, Ray SM, Ritger KA, Rowlinson MC, Sabuwala N, Schiller TM, Schwartz LE, Spitters C, Thomson DB, Tresgallo RR, Valois P, Goswami ND; BPaL Implementation Group. Implementation of Bedaquiline, Pretomanid, and Linezolid in the United States: Experience Using a Novel All-Oral Treatment Regimen for Treatment of Rifampin-Resistant or Rifampin-Intolerant Tuberculosis Disease. Clin Infect Dis. 2023 Oct 5;77(7):1053-1062. doi: 10.1093/cid/ciad312.
Reference Type
BACKGROUND
Pea F, Viale P, Cojutti P, Del Pin B, Zamparini E, Furlanut M. Therapeutic drug monitoring may improve safety outcomes of long-term treatment with linezolid in adult patients. J Antimicrob Chemother. 2012 Aug;67(8):2034-42. doi: 10.1093/jac/dks153. Epub 2012 May 2.
Reference Type
BACKGROUND
Schwartz D, Lellouch J. Explanatory and pragmatic attitudes in therapeutical trials. J Chronic Dis. 1967 Aug;20(8):637-48. doi: 10.1016/0021-9681(67)90041-0. No abstract available.
Reference Type
BACKGROUND
Ford I, Norrie J. Pragmatic Trials. N Engl J Med. 2016 Aug 4;375(5):454-63. doi: 10.1056/NEJMra1510059. No abstract available.
Reference Type
BACKGROUND
UNAIDS. Global AIDS Update. Geneva 2023.
Reference Type
BACKGROUND
Brust JC, Shah NS, Scott M, Chaiyachati K, Lygizos M, van der Merwe TL, Bamber S, Radebe Z, Loveday M, Moll AP, Margot B, Lalloo UG, Friedland GH, Gandhi NR. Integrated, home-based treatment for MDR-TB and HIV in rural South Africa: an alternate model of care. Int J Tuberc Lung Dis. 2012 Aug;16(8):998-1004. doi: 10.5588/ijtld.11.0713. Epub 2012 Jun 5.
Reference Type
BACKGROUND
Loveday M, Wallengren K, Voce A, Margot B, Reddy T, Master I, Brust J, Chaiyachati K, Padayatchi N. Comparing early treatment outcomes of MDR-TB in decentralised and centralised settings in KwaZulu-Natal, South Africa. Int J Tuberc Lung Dis. 2012 Feb;16(2):209-15. doi: 10.5588/ijtld.11.0401.
Reference Type
BACKGROUND
Department of Health South Africa. Interim clinical guidance for the implementation of injectable-free regimens for rifampicin-resistant tuberculosis in adults, adolescents and children. 2018.
Reference Type
BACKGROUND
Medecins Sans Frontieres. South Africa Becomes First Country to Include New, More Effective DR-TB Drug in Standard Treatment https://wwwdoctorswithoutbordersorg/latest/south-africa-becomes-first-country-include-new-more-effective-dr-tb-drug-standard-treatment (accessed August 9, 2023) 2018.
Reference Type
BACKGROUND
Ndjeka N, Conradie F, Schnippel K, Hughes J, Bantubani N, Ferreira H, Maartens G, Mametja D, Meintjes G, Padanilam X, Variava E, Pym A, Pillay Y. Treatment of drug-resistant tuberculosis with bedaquiline in a high HIV prevalence setting: an interim cohort analysis. Int J Tuberc Lung Dis. 2015 Aug;19(8):979-85. doi: 10.5588/ijtld.14.0944.
Reference Type
BACKGROUND
U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS. Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1. [July 2017]. Available from: https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf (accessed Sep 10, 2023).
Reference Type
BACKGROUND
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2024-16182
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.
Trial of a Six-Month Regimen of High-Dose Rifampicin, High-Dose Isoniazid, Linezolid, and Pyrazinamide Versus a Standard Nine-Month Regimen for the Treatment of Adults and Adolescents With Tuberculous Meningitis
NCT05383742
RECRUITING
PHASE2
Treatment Shortening of MDR-TB Using Existing and New Drugs
NCT02619994
COMPLETED
PHASE2
Efficacy and Tolerability of Bedaquiline, Delamanid, Levofloxacin, Linezolid, and Clofazimine to Treat MDR-TB
NCT03828201
RECRUITING
PHASE2
Drug Interaction Study Between Linezolid and Clarithromycin in Tuberculosis Patients
NCT01521364
COMPLETED
PHASE4
Asymptomatic Colonization With S. Aureus After Therapy With Linezolid or Clindamycin for Acute Skin Infections
NCT01619410
TERMINATED
NA
Linezolid for Treatment of Nontuberculous Mycobacterial Diseases
NCT03220074
COMPLETED
PHASE4
GSK1322322 Versus Linezolid in the Treatment of Acute Bacterial Skin and Skin Structure Infection
NCT01209078
COMPLETED
PHASE2
Investigation of the Correlation Between Plasma Concentration of Linezolid Antibiotic and Treatment Response and Adverse Reactions
NCT03126890
UNKNOWN
Retrospective Real-word Study of Linezolid for the Treatment of Tuberculous Meningitis
NCT03898635
UNKNOWN
Skin Structure Infections With Suspected or Proven Methicillin-Resistant Staphylococcus Aureus (MRSA)
NCT00087490
COMPLETED
PHASE4
To Evaluate the Safety, Tolerability, and Efficacy of TMC207 as Part of an Individualized Multi-drug Resistant Tuberculosis (MDR-TB) Treatment Regimen in Participants With Sputum Smear-positive Pulmonary MDR-TB.
NCT00910871
COMPLETED
PHASE2
Randomized Clinical Trial to Compare a Regimen of Trimethoprim-sulfamethoxazole Plus Rifampicin With a Regimen of Linezolid in the Treatment of Methicillin-Resistant Staphylococcus Aureus (MRSA) Infection
NCT00711854
COMPLETED
PHASE4
Linezolid for the Treatment of Infections Caused by Methicillin Resistant Staphylococcus Aureus in Japan
NCT00150332
COMPLETED
PHASE3
TMC207-TiDP13-C208: Anti-bacterial Activity, Safety, and Tolerability of TMC207 in Participants With Multi-drug Resistant Mycobacterium Tuberculosis (MDR-TB).
NCT00449644
COMPLETED
PHASE2
Drug Use Investigation Of Zyvox (Linezolid) (Regulatory Post Marketing Commitment Plan)
NCT00666276
COMPLETED
Building Evidence for Advancing New Treatment for Rifampicin Resistant Tuberculosis (RR-TB) Comparing a Short Course of Treatment (Containing Bedaquiline, Delamanid and Linezolid) With the Current South African Standard of Care
NCT04062201
COMPLETED
PHASE3
Phase 3 Safety and Efficacy Study of I.V. Iclaprim v Linezolid in cSSSI (ASSIST-1)
NCT00299520
COMPLETED
PHASE3
Phase II Clinical Study of Contezolid for the Treatment of Tuberculous Meningitis
NCT06811025
ENROLLING_BY_INVITATION
PHASE1/PHASE2
Linezolid for Syphilis Pilot Study
NCT05548426
RECRUITING
PHASE2
Efficacy and Safety of Ceftaroline Versus Linezolid in Subjects With Complicated Skin and Skin Structure Infections
NCT00633152
COMPLETED
PHASE2
Nosocomial Pneumonia With Suspected Or Proven Methicillin-Resistant Staphylococcus Aureus (MRSA)
NCT00084266
COMPLETED
PHASE4
6 Months of Bedaquiline(BDQ), Delamanid(DLM), Linezolid(LZD) and Levofloxacin(LFX) in RR-TB Patients in Hubei Province
NCT07198685
NOT_YET_RECRUITING
NA
A Phase 2a Study, Effect of Vancomycin With vs Without Delpazolid (LCB01-0371) in Patients With MRSA Bacteremia
NCT05225558
TERMINATED
PHASE2
A Study to Evaluate the Safety and Efficacy of Azithromycin in Individual Patients With Serious Nontuberculous Mycobacterial Disease Who Are Failing or Intolerant of Other Available Therapy
NCT00002085
COMPLETED
NA
Clinical Evaluation of the Residual Antimicrobial Activity
NCT04495920
COMPLETED
EARLY_PHASE1