Gram-Positive Bacterial InfectionsPhase 3LINEMAPNCT06444802
Model-informed Precision Dosing for Linezolid
A Phase 3 study testing Linezolid in people with Gram-Positive Bacterial Infections, run by University of Hamburg-Eppendorf.
Trial summary
Study Rationale: Previous in vitro and retrospective in vivo studies suggest that optimal linezolid concentrations (between 2 and 7 mg/L) achieve clinical efficacy and microbiological eradication while minimizing side effects like thrombocytopenia and the emergence of resistance. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gram-Positive Bacterial Infections
- What is being tested?
- Linezolid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2024to 30 Jun 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥ 18 years of age
- Linezolid treatment is indicated or has been started due to pneumonia, skin or soft tissue infection; the patient has received no more than 2 infusions of 600 mg linezolid each
- with written informed consent of the patient or
- with written informed consent of his/her legal representative or
- after using the option of inclusion via spouse according to § 1358 BGB or
- after application of the independent consultant procedure
- Patients of childbearing age: negative pregnancy test
Who cannot join
- Patients receiving antibiotics active against Gram-positive bacteria at the same time of linezolid
- Infection other than pneumonia, skin or soft tissue infection, especially tuberculosis, endocarditis and osteomyelitis
- Death is deemed imminent and inevitable
- Pregnancy
- Lactation/breastfeeding
Trial locations and contacts
No sites are listed yet.
Dominic Wichmann, Prof contact
About this study
Official title: Model-informed Precision Dosing for Linezolid: a Pilot Randomized Clinical Trial
Study Rationale: Previous in vitro and retrospective in vivo studies suggest that optimal linezolid concentrations (between 2 and 7 mg/L) achieve clinical efficacy and microbiological eradication while minimizing side effects like thrombocytopenia and the emergence of resistance. No prospective or randomized clinical trial has confirmed these findings, and there is no consensus on how to adjust linezolid dosing to achieve optimal drug concentrations.
Objectives: The primary objective is to determine if model-informed precision dosing optimizes linezolid dosing to achieve therapeutic trough concentrations compared to a standard dose. Secondary objectives include assessing the PK/PD profile, investigating the prevalence of linezolid resistance among gram-positive bacteria, assessing microbiological resolution of infection, and evaluating the safety and tolerability of linezolid.
Read more
Methodology: This study is an open, monocentric pilot randomized controlled trial with two arms: standard dose therapy versus dose adjustment based on model-informed precision dosing using therapeutic drug monitoring and PK/PD targets developed in TMDx software.
Sample Size: 28 patients, 14 in each group. Assumptions are based on only 25% of patients in intensive care achieving the optimal therapeutic range with standard dosing, compared to an expected 80% achieving this with model-informed precision dosing.
Selection Criteria: Adult patients (18+ years) already starting linezolid treatment for gram-positive infections, expected to require treatment beyond the next calendar day. Exclusions include imminent death, expected or confirmed pregnancy, expected linezolid treatment of less than 4 days or more than 4 weeks.
Outcomes: The primary endpoint is defined as the difference in the proportion of patients in the intervention and in the control groups who maintained a trough linezolid concentration of 2 to 7 mg/L on Day 7 and Day 13.
- Conditions
- Gram-Positive Bacterial Infections
- Being tested
- Linezolid
- Keywords
- Linezolid, PK-PD Model, TDM
- Medical subject headings
- Gram-Positive Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LinezolidDrug
Linezolid dosing will be adapted according to a model informed precision dosing (TDMx)
| Study group | Role | What they receive |
|---|---|---|
| Linezolid Dosing based on TDMx | Experimental | Linezolid dosing based on a model-informed precision dosing (TDMx) Receives: Drug: Linezolid |
| Standard Linezolid dosing | Active comparator | Patient will receive Linezolid at standard dose Receives: Drug: Linezolid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Through concentration in the target
The primary endpoint is defined as the likehood in achieving a trough linezolid concentration of 2 to 8 mg/L on Day 7
Measured: Day 7 of linezolid treatment
Secondary outcomes (6)
Pharmacokinetic:
Percentage of the dosing interval while drug concentration remains above the MIC (f%T > MIC)
Measured: Day 7 and day 13 of linezolid treatment
Thrombocytopenia
Median variation of platelets count after the start up to end of linezolid treatment
Measured: From the start of linezolid treatment and up to 14 days
lactic acidosis and peripheral neuropathy
Frequency of lactic acidosis and peripheral neuropathy
Measured: From the start of linezolid treatment and up to 14 days
Microbiology
Time to microbiologic eradication is calculated as the interval between the first isolation of a Gram-positive pathogen causing the infection and the first negative culture from the same type of biological material
Measured: From the start of linezolid treatment and up to 14 days
Microbiology
Time to development of resistance to linezolid in Gram-positive bacteria is calculated as the interval in days between the first isolation of a specific bacteria species sensitive to linezolid and the first isolation of the same species showing resistance, in any type of biological material.
Measured: From the start of linezolid treatment and up to 14 days
Microbiology
Rate of Relapse of gram-positive infection (growth of the same gram-positive organism in the blood culture or in another primarily site infected up to EOF).
Measured: At the end of treatment up to the end of 30 day follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2024
- Study start1 Sep 2024 (estimated)
- Primary completion28 Feb 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gram-Positive Bacterial InfectionsStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Hamburg-Eppendorf
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Flaminia Olearo, University of Hamburg-Eppendorf
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06444802
- Sponsor's protocol ID
- TTU 08.922
- Acronym
- LINEMAP
- Status last verified
- May 2024
- First submitted
- 24 May 2024
- Last updated
- 6 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Model-informed Precision Dosing for Linezolid: a Pilot Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT06444802
- Acronym / sponsor ID
- LINEMAP / TTU 08.922
- Conditions
- Gram-Positive Bacterial Infections
- Keywords
- Linezolid, PK-PD Model, TDM
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- University of Hamburg-EppendorfUniversity, hospital or other
- Study start
- 1 Sep 2024 (estimated)
- Primary completion
- 28 Feb 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 6 Jun 2024 (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.
Study Rationale: Previous in vitro and retrospective in vivo studies suggest that optimal linezolid concentrations (between 2 and 7 mg/L) achieve clinical efficacy and microbiological eradication while minimizing side effects like thrombocytopenia and the emergence of resistance. No prospective or randomized clinical trial has confirmed these findings, and there is no consensus on how to adjust linezolid dosing to achieve optimal drug concentrations.
Objectives: The primary objective is to determine if model-informed precision dosing optimizes linezolid dosing to achieve therapeutic trough concentrations compared to a standard dose. Secondary objectives include assessing the PK/PD profile, investigating the prevalence of linezolid resistance among gram-positive bacteria, assessing microbiological resolution of infection, and evaluating the safety and tolerability of linezolid.
Methodology: This study is an open, monocentric pilot randomized controlled trial with two arms: standard dose therapy versus dose adjustment based on model-informed precision dosing using therapeutic drug monitoring and PK/PD targets developed in TMDx software.
Sample Size: 28 patients, 14 in each group. Assumptions are based on only 25% of patients in intensive care achieving the optimal therapeutic range with standard dosing, compared to an expected 80% achieving this with model-informed precision dosing.
Selection Criteria: Adult patients (18+ years) already starting linezolid treatment for gram-positive infections, expected to require treatment beyond the next calendar day. Exclusions include imminent death, expected or confirmed pregnancy, expected linezolid treatment of less than 4 days or more than 4 weeks.
Outcomes: The primary endpoint is defined as the difference in the proportion of patients in the intervention and in the control groups who maintained a trough linezolid concentration of 2 to 7 mg/L on Day 7 and Day 13.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Linezolid Dosing based on TDMx | Experimental | Drug: LinezolidLinezolid dosing based on a model-informed precision dosing (TDMx) |
| Standard Linezolid dosing | Active comparator | Drug: LinezolidPatient will receive Linezolid at standard dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- ≥ 18 years of age
- Linezolid treatment is indicated or has been started due to pneumonia, skin or soft tissue infection; the patient has received no more than 2 infusions of 600 mg linezolid each
- with written informed consent of the patient or
- with written informed consent of his/her legal representative or
- after using the option of inclusion via spouse according to § 1358 BGB or
Key exclusion criteria (5 listed)
- Patients receiving antibiotics active against Gram-positive bacteria at the same time of linezolid
- Infection other than pneumonia, skin or soft tissue infection, especially tuberculosis, endocarditis and osteomyelitis
- Death is deemed imminent and inevitable
- Pregnancy
- Lactation/breastfeeding
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 |
|---|---|---|
| LinezolidLinezolid dosing will be adapted according to a model informed precision dosing (TDMx) | Drug | Linezolid Dosing based on TDMx, Standard Linezolid dosing |
Primary outcome
Through concentration in the target
Time frame: Day 7 of linezolid treatment
The primary endpoint is defined as the likehood in achieving a trough linezolid concentration of 2 to 8 mg/L on Day 7
6 secondary outcomes
Pharmacokinetic:
Time frame: Day 7 and day 13 of linezolid treatment
Thrombocytopenia
Time frame: From the start of linezolid treatment and up to 14 days
lactic acidosis and peripheral neuropathy
Time frame: From the start of linezolid treatment and up to 14 days
Microbiology
Time frame: From the start of linezolid treatment and up to 14 days
Microbiology
Time frame: From the start of linezolid treatment and up to 14 days
Microbiology
Time frame: At the end of treatment up to the end of 30 day follow-up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2024.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Dominic Wichmann, Prof contact
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Linezolid in people with Gram-Positive Bacterial Infections, run by University of Hamburg-Eppendorf.
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 7 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 6 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Flaminia Olearo, MD (00491738815647, f.olearo@uke.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Through concentration in the target (time frame: Day 7 of linezolid treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Jun 2024; AzTrials last refreshed its copy on 28 Oct 2026.