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

May 11, 2026 updated by: Marco Schiuma

Tolérance du Linézolide Pendant le Régime BPaL Avec Personnalisation de la Posologie Basée Sur la Surveillance Thérapeutique Des Médicaments (TDM) au Cours du Traitement de la Tuberculose Multirésistante

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Guinea
      • Conakry, Guinea
        • Recruiting
        • Centre de Santé de Tombolia
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 1. Confirmed diagnosis of MDR-TB
  • 2. Linezolid prescribed as part of the BPaL/BPaL-M regimen
  • 3. Age 15 years or older
  • 4. Informed consent obtained from the participant or assent from the parent/legal guardian for participants under 18 years of age.

Exclusion Criteria:

  • 1. Pregnancy or breastfeeding
  • 2. Severe liver or kidney failure
  • 3. Known hypersensitivity to linezolid
  • 4. Concomitant use of medications with drug interactions potential with linezolid

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Group A: linezolid 600 mg standard dose. Only TDM monitoring
Linezolid will be administered at the recommended dose of 600 mg. The linezolid level will be measured for each patient once a week during the first month (4 blood samples), then once a month for the following 5 months (5 blood samples) to complete the 6-month regimen (at least 9 blood samples for each patient). One additional sample will be taken if linezolid-related side effects appear. No changes to the linezolid dosage will be made except as directed in accordance with the national guidelines for the management of MDR-TB.
Experimental: Group B: linezolid dose personalization based on TDM
Linezolid will be initially administered at the recommended dose of 600 mg. The linezolid level will be measured for each patient once a week during the first month (4 blood samples), then once a month for the following 5 months (5 blood samples) to complete the 6-month regimen (at least 9 blood samples for each patient). Additional samples will be taken if linezolid-related side effects appear or if the trough linezolid concentration in the blood does not reach the reference range of 0.6-2 mg/l. The dosage of linezolid will be modified according to the TDM
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of linezolid related side effects.
Time Frame: From enrollment to the end of treatment at 6 months
The primary objective is to evaluate the variation in the rate of occurrence of adverse events between patients who undergo a modification of the linezolid dose based on the TDM and patients taking linezolid standard dose. We hypothesize that patients who under go linezolid dose personalization based on TDM will maintain linezolid blood levels within the therapeutic range (0.6-2 mg/l). This could result in a different rate in linezolid related side effects between the two groups
From enrollment to the end of treatment at 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility of linezolid dosage personalization based on TDM in low resources setting
Time Frame: From enrollment to the end of treatment at 6 months
The objective is to determine if TDM has a role in the optimization of linezolid dosage in TB-MDR patients in a setting similar to Guinea. The feasibility and implementability of the method will be assessed by comparing the number of blood samples actually collected from each participant with the number of samples scheduled according to the predefined theoretical sampling time set for each participant.
From enrollment to the end of treatment at 6 months
Treatment outcome
Time Frame: From the enrollment to the end of the treatment at 6 months
The objective is to evaluate the treatment outcome (defined by WHO as: treatment failed, cured, treatment completed, died, lost to follow up, treatment success, sustained treatment success) in patients who undergo a modification of the linezolid dose based on TDM and patients taking linezolid standard dose.
From the enrollment to the end of the treatment at 6 months
Linezolid TDM trends
Time Frame: From enrollment to the end of treatment at 6 months
The objective is to describe the TDM values during the treatment, define variations in the distribution of TDM throughout treatment in order to identify potential common trends (for example median lower values at the beginning of the treatment for all the patients, linked to higher inflammation, increased values at the end of the treatment for linezolid accumulation)
From enrollment to the end of treatment at 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Marco Schiuma

Collaborators

ASST Fatebenefratelli Sacco
University of Milan
Damien Foundation

Investigators

  • Study Director: Marco Schiuma, ASST Fatebenefratelli Sacco, Luigi Sacco University Hospital, Milan, Italy
  • Principal Investigator: Souleymane Hassane Harouna, Action Daminen Guinée

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2026

Primary Completion (Estimated)

October 1, 2027

Study Completion (Estimated)

April 1, 2028

Study Registration Dates

First Submitted

March 10, 2026

First Submitted That Met QC Criteria

March 13, 2026

First Posted (Actual)

March 17, 2026

Study Record Updates

Last Update Posted (Actual)

May 13, 2026

Last Update Submitted That Met QC Criteria

May 11, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 079/CNERS/25

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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