Model-informed Precision Dosing for Linezolid

NCT ID: NCT06444802

Last Updated: 2024-06-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-01
• Study Completion Date: 2026-06-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Linezolid Dosing based on TDMx

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

Group Type: EXPERIMENTAL

Linezolid

Intervention Type: DRUG

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

Standard Linezolid dosing

Patient will receive Linezolid at standard dose

Group Type: ACTIVE_COMPARATOR

Linezolid

Intervention Type: DRUG

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

Interventions

Linezolid

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. ≥ 18 years of age

2. 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

3. with written informed consent of the patient or

4. with written informed consent of his/her legal representative or

5. after using the option of inclusion via spouse according to § 1358 BGB or

6. after application of the independent consultant procedure

7. Patients of childbearing age: negative pregnancy test

Exclusion Criteria

1. Patients receiving antibiotics active against Gram-positive bacteria at the same time of linezolid

2. Infection other than pneumonia, skin or soft tissue infection, especially tuberculosis, endocarditis and osteomyelitis

3. Death is deemed imminent and inevitable

4. Pregnancy

5. Lactation/breastfeeding

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Hamburg-Eppendorf

OTHER

Sponsor Role: lead

Responsible Party

Flaminia Olearo

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Flaminia Olearo, MD

Role: CONTACT

f.olearo@uke.de

00491738815647

Dominic Wichmann, Prof

Role: CONTACT

d.wichmann@uke.de

Other Identifiers

TTU 08.922

Identifier Type: -

Identifier Source: org_study_id