Therapeutic Drug Monitoring for Linezolid in the Treatment of Rifampin-resistant Tuberculosis

NCT06590428 | Recruiting DMC

• 2 other identifiers: 2024-16182R01AI184416
• Study Type: interventional
• Target: 280
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Drug-resistant Tuberculosis; Rifampin-resistant Tuberculosis

Keywords

HIV Status; Therapeutic Drug Monitoring; anti-Tuberculosis activity; Linezolid

Outcome Measures

Primary Outcomes (1)

• Discontinuation of Linezolid or non-TDM guided dose reduction

  Linezolid (LZD) discontinuation for any cause along with non-TDM-guided LZD dose reduction will be assessed. The number of participants who discontinue LZD (defined as an interruption \> 2 weeks in duration), including self-discontinuation by the patient or a decision by the provider to temporarily or permanently discontinue LZD, OR have a non-TDM-guided dose-reduction in response to an adverse event, will be summarized by study arm using basic descriptive statistics.

  Within 6 months after initiation of LZD therapy

Secondary Outcomes (5)

• Evidence of Linezolid Toxicity

  Within 6 months after initiation of LZD therapy

• Unsuccessful final Tuberculosis (TB) end-of-treatment outcome

  After 6 months, and up to 12 months after initiation of LZD therapy

• Emergence of new phenotypic resistance to Linezolid

  Within 6 months after initiation of LZD therapy

• TB-free survival

  12 months after initiation of LZD therapy

• Non-TDM-guided dose reduction of linezolid

  Within 6 months after initiation of LZD therapy

Study Arms (2)

Therapeutic Drug Monitoring (TDM)

OTHER

Participants in the TDM arm will have their linezolid dose reduced if their trough concentration is greater than 2.5 mg/L

Other: Therapeutic Drug Monitoring for Linezolid

Standard of Care (SOC)

NO INTERVENTION

Participants in the SOC arm will have their linezolid adjusted or held if they develop clinical adverse events.

Interventions

Therapeutic Drug Monitoring for Linezolid OTHER

TDM with dose adjustment for trough concentration \>2.5 mg/L LZD

Therapeutic Drug Monitoring (TDM)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male or female patient \> 18 years of age
• Microbiological confirmation of rifampicin-resistant tuberculosis (e.g., phenotypic or genotypic 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 rifampicin-resistant tuberculosis (RR-TB) treatment regimen containing linezolid, no more than 14 days prior to randomization
• HIV status is known and confirmed
• Both HIV-positive and HIV-negative individuals are eligible
• If an individual reports unknown HIV status, 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

You may not qualify if:

• Severe medical condition with expected death in the next 7 days
• Pregnant at time of screening
• Initial linezolid dose \< 600mg daily
• Severe form of extrapulmonary TB (i.e., meningitis, pericarditis, or osteomyelitis)
• Unlikely to follow-up at Nkqubela Hospital based on location of residence

Sponsors & Collaborators

• University of Cape Town: collaborator
• St George's, University of London: collaborator
• Emory University: collaborator
• Columbia University: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Albert Einstein College of Medicine: lead
• National Department of Health, South Africa: collaborator

Study Sites (1)

Nkqubela TB Specialist Hospital

East London, Eastern Cape, 5206, South Africa

RECRUITING

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MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant

Interventions

Linezolid

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• James CM Brust, MD

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

• Gary Maartens, MBChB

  University of Cape Town

  PRINCIPAL INVESTIGATOR

Central Study Contacts

James CM Brust, MD

CONTACT

718-920-6482; james.brust@einsteinmed.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 9, 2024
• First Posted: September 19, 2024
• Study Start: April 7, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Scientific data included in published manuscripts will be available at the time of publication or the end of the award, whichever comes first; all other generated scientific data will be shared no later than the end of the award. Data will be made available for an indefinite period or until Emory University requests that it be withdrawn.
• Access Criteria: All de-identified study data not designated as restricted use will be made available to the research community upon request and approval by study MPIs. Code used to perform statistical analysis will be deposited in a publicly available repository or may be requested from the investigators to ensure others can seek to reproduce the results, if desired. Public use and restricted access study data and associated documentation will be made available to the research community free of charge through the Emory Dataverse, an open data repository intended for the preservation, discoverability and accessibility of data produced by the Emory University research community, or other appropriate data repository.

Locations

ZA (1)