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Linezolid Tolerance During the BPaL Regimen With Dosage Personalization Based on Therapeutic Drug Monitoring (TDM) During Multidrug-Resistant Tuberculosis Treatment

NCT07477119 · Status: RECRUITING · Phase: PHASE4 · Type: INTERVENTIONAL · Enrollment: 150

Last updated 2026-05-13

No results posted yet for this study

Summary

Multidrug-resistant tuberculosis (MDR-TB) poses a significant challenge to global public health.

Globally, the World Health Organization (WHO) estimates the number at 400,000 patients with MDR-TB for 2023. Only 44% were diagnosed and put on treatment, the therapeutic success rate of the 2021 cohort is only 68%.

In Guinea, the number of patients with MDR-TB is estimated at 450, and the treatment success rate is 74% for the 2021 cohort, primarily with the 9-months short oral regimen.

Since 2022, the WHO has recommended the use of the 6-month short course of BPaL/BPaL-M for national tuberculosis control programs and Guinea began implementing this new regime within the programmatic framework starting in January 2025.

Linezolid, a key component of new therapeutic regimens such as BPaL/BPaL-M, shows high bactericidal activity, although it is associated with serious adverse effects in a high percentage of patients, including myelosuppression, neuropathy and, in some cases, fatal lactic acidosis. In particular, peripheral neuropathy, an adverse event often irreversible that may lead to linezolid and the BPaL/BPaL-M regimen discontinuation, is reported in approximately 24% of patients receiving linezolid at 600 mg.

A linezolid blood trough level of above 2 mg/l is associated with side effects, but its pharmacokinetics varies considerably between individuals and over time.

There is little data on the role of therapeutic drug monitoring (TDM) in guiding its administration, some studies showing how the standard dose of 600 mg could exceed the toxicity target and the reduced dose of 300 mg might not achieve the target efficacy.

The main objective of this study is to determine the role of TDM in the optimization of linezolid dosage in TB-MDR patients treated with the BPaL/BPaL-M regimen.

The specific objectives aim to evaluate:

* the variation in the occurrence of adverse events between patients who undergo a modification of the linezolid dose based on the TDM and patients taking linezolid standard dose
* the treatment outcome in patients who undergo a modification of the linezolid dose based on TDM and patients taking linezolid standard dose
* variations in the distribution of TDM throughout treatment in order to identify potential common trends.

Conditions

  • Linezolid
  • Tuberculosis Multi Drug Resistant Active
  • Therapeutic Drug Monitoring (TDM)

Interventions

DRUG

Linezolid dose personalization based on TDM

The dosage of linezolid will be modified according to the TDM as follows: if \> 2 mg/l the dosage will be decreased by 300 mg (minimum 300 mg every second day, TDM repeated after one week); if \< 0.6 mg/l the dosage will be increased by 300 mg (maximum 1200 mg, TDM repeated after one week); if between 0.6 and 2 mg/l the dosage will not be changed (regular TDM timepoints)

Sponsors & Collaborators

  • ASST Fatebenefratelli Sacco

    collaborator OTHER

  • University of Milan

    collaborator OTHER

  • Damien Foundation

    collaborator OTHER

  • Marco Schiuma

    lead OTHER

Principal Investigators

  • Marco Schiuma · ASST Fatebenefratelli Sacco, Luigi Sacco University Hospital, Milan, Italy

  • Souleymane Hassane Harouna · Action Daminen Guinée

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
15 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2026-04-30
Primary Completion
2027-10-31
Completion
2028-04-30

Countries

  • Guinea

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07477119 on ClinicalTrials.gov