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
- Are there results?
- Not yet: the study is under way
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.
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07477119
- Acronym / sponsor ID
- PLOT-TB / 079/CNERS/25
- Keywords
- linezolid, TDM, Therapeutic Drug Monitoring, MDR-TB, Guinea, Adverse Drug Reaction, Peripheral Neuropathy, Myelosuppression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Marco SchiumaUniversity, hospital or other
- Collaborators
- ASST Fatebenefratelli Sacco, University of Milan, Damien Foundation
- Study start
- Apr 2026 (estimated)
- Primary completion
- Oct 2027 (estimated)
- Study completion
- Apr 2028 (estimated)
- First posted
- 17 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 | Drug: Linezolid dose personalization based on TDMLinezolid 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 |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Linezolid dose personalization based on TDMThe 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) | Drug | Group B: linezolid dose personalization based on TDM |
Primary outcome
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
3 secondary outcomes
Feasibility of linezolid dosage personalization based on TDM in low resources setting
Time frame: 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
Linezolid TDM trends
Time frame: From enrollment to the end of treatment at 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2026.
- Background: PubMed 34543098Abdelwahab 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.
- Background: PubMed 36053506Conradie 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.
- Background: PubMed 36630546WHO 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/
- BackgroundGlobal tuberculosis report 2024. Geneva: World Health Organization; 2024. Licence: CC BY-NC-SA 3.0 IGO
- Background: PubMed 20042919Alffenaar 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.
- Background: PubMed 24834239Pourhoseingholi MA, Vahedi M, Rahimzadeh M. Sample size calculation in medical studies. Gastroenterol Hepatol Bed Bench. 2013 Winter;6(1):14-7.
- BackgroundDaniel, Wayne W. Biostatistics: a foundation for analysis in the health sciences. Vol. 129. Wiley, 1978.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marco Schiuma study director
ASST Fatebenefratelli Sacco, Luigi Sacco University Hospital, Milan, Italy
Souleymane Hassane Harouna principal investigator
Action Daminen Guinée
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Guinea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marco Schiuma (+393284931986, schiuma.marco@asst-fbf-sacco.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of linezolid related side effects. (time frame: From enrollment to the end of treatment at 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07477119, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2026.