Model-informed Precision Dosing for Linezolid

NCT06444802 | Not Yet Recruiting Phase 3

• 1 other identifier: TTU 08.922
• Study Type: interventional
• Target: 28
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Gram-Positive Bacterial Infections

Keywords

Linezolid; PK-PD Model; TDM

Outcome Measures

Primary Outcomes (1)

• 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

  Day 7 of linezolid treatment

Secondary Outcomes (6)

• Pharmacokinetic:

  Day 7 and day 13 of linezolid treatment

• Thrombocytopenia

  From the start of linezolid treatment and up to 14 days

• lactic acidosis and peripheral neuropathy

  From the start of linezolid treatment and up to 14 days

• Microbiology

  From the start of linezolid treatment and up to 14 days

• Microbiology

  From the start of linezolid treatment and up to 14 days

Study Arms (2)

Linezolid Dosing based on TDMx

EXPERIMENTAL

Linezolid dosing based on a model-informed precision dosing (TDMx)

Drug: Linezolid

Standard Linezolid dosing

ACTIVE COMPARATOR

Patient will receive Linezolid at standard dose

Drug: Linezolid

Interventions

Linezolid DRUG

Linezolid dosing will be adapted according to a model informed precision dosing (TDMx)

Linezolid Dosing based on TDMx; Standard Linezolid dosing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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 application of the independent consultant procedure
• Patients of childbearing age: negative pregnancy test

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Hamburg-Eppendorf: lead

MeSH Terms

Conditions

Gram-Positive Bacterial Infections

Interventions

Linezolid

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Flaminia Olearo, MD

CONTACT

00491738815647; f.olearo@uke.de

Dominic Wichmann, Prof

CONTACT

d.wichmann@uke.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 24, 2024
• First Posted: June 6, 2024
• Study Start: September 1, 2024
• Primary Completion: February 28, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: June 6, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share