LinezolidPhase 4PLOT-TBNCT07477119
Linezolid Tolerance During the BPaL Regimen With Dosage Personalization Based on Therapeutic Drug Monitoring (TDM) During Multidrug-Resistant Tuberculosis Treatment
A Phase 4 study testing Linezolid dose personalization based on TDM in people with Linezolid and Tuberculosis Multi Drug Resistant Active, run by Marco Schiuma at 1 site in Guinea.
Trial 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%. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Linezolid, Tuberculosis Multi Drug Resistant Active, Therapeutic Drug Monitoring (TDM)
- What is being tested?
- Linezolid dose personalization based on TDM
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteGuinea
- Study dates
- Apr 2026to Apr 2028
- Phase
- Phase 4
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 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Guinea1 site, 1 recruiting
- Recruiting
Centre de Santé de Tombolia
Conakry
Souleymane Hassane Harouna, +224620717593, hassoul20@yahoo.fr
About this study
Official title: 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%.
Read more
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.
- Being tested
- Linezolid dose personalization based on TDM
- Keywords
- linezolid, TDM, Therapeutic Drug Monitoring, MDR-TB, Guinea, Adverse Drug Reaction, Peripheral Neuropathy, Myelosuppression, Tuberculosis
- Medical subject headings
- Tuberculosis, Multidrug-Resistant, Drug-Related Side Effects and Adverse Reactions, Peripheral Nervous System Diseases, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Linezolid dose personalization based on TDMDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| Group A: linezolid 600 mg standard dose. Only TDM monitoring | No intervention | 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. |
| Group B: linezolid dose personalization based on TDM | Experimental | 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 Receives: Drug: Linezolid dose personalization based on TDM |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of linezolid related side effects.
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
Measured: From enrollment to the end of treatment at 6 months
Secondary outcomes (3)
Feasibility of linezolid dosage personalization based on TDM in low resources setting
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.
Measured: From enrollment to the end of treatment at 6 months
Treatment outcome
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.
Measured: From the enrollment to the end of the treatment at 6 months
Linezolid TDM trends
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)
Measured: From enrollment to the end of treatment at 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2026
- Study startApr 2026 (estimated)
- Primary completionOct 2027 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for LinezolidStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Marco Schiuma
- Sponsor type
- University, hospital or other
- Collaborators
- ASST Fatebenefratelli Sacco, University of Milan, Damien Foundation
- Responsible party
- Sponsor-investigator, Marco Schiuma, ASST Fatebenefratelli Sacco
- Investigators
- Marco Schiuma, Study director, ASST Fatebenefratelli Sacco, Luigi Sacco University Hospital, Milan, ItalySouleymane Hassane Harouna, Principal investigator, Action Daminen Guinée
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07477119
- Sponsor's protocol ID
- 079/CNERS/25
- Acronym
- PLOT-TB
- Status last verified
- May 2026
- First submitted
- 10 Mar 2026
- Last updated
- 13 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 34543098Conradie 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.
PubMed 36053506WHO consolidated guidelines on tuberculosis: Module 4: treatment - drug-resistant tuberculosis treatment, 2022 update [Internet]. Geneva: World Health Organization; 2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK588564/
PubMed 36630546Global tuberculosis report 2024. Geneva: World Health Organization; 2024. Licence: CC BY-NC-SA 3.0 IGO
Alffenaar JW, Kosterink JG, van Altena R, van der Werf TS, Uges DR, Proost JH. Limited sampling strategies for therapeutic drug monitoring of linezolid in patients with multidrug-resistant tuberculosis. Ther Drug Monit. 2010 Feb;32(1):97-101. doi: 10.1097/FTD.0b013e3181cc6d6f.
PubMed 20042919Pourhoseingholi MA, Vahedi M, Rahimzadeh M. Sample size calculation in medical studies. Gastroenterol Hepatol Bed Bench. 2013 Winter;6(1):14-7.
PubMed 24834239Daniel, Wayne W. Biostatistics: a foundation for analysis in the health sciences. Vol. 129. Wiley, 1978.