Pharmacokinetic and Pharmacodynamic Evaluation of Linezolid Administered Intravenously in MRSA-positive, Morbidly Obese Patients With Pneumonia (UGENT_LIMOP)

The objectives of the study are:

(i) to evaluate the proportion of patients who attain a T>MIC (Minimum Inhibitory Concentration) of 100% and the time frame in which they do so. The investigators therefore plan to measure unbound linezolid trough concentrations before administration of the second, third, fourth and fifth dose. Furthermore, the investigators will assess the AUC0 - 24h/MIC in all study subjects. Therefore, multiple plasma samples will be drawn after the fourth or fifth dose, when steady state conditions are reached.

(ii) to describe the pharmacokinetic variability of unbound linezolid concentrations in this cohort using a population pharmacokinetic model and to assess the expected probability of target attainment (PTA) by MIC against MRSA.

Twenty adult, MRSA-positive, morbidly obese patients with clinically and radiologically documented pneumonia are to be included. Therefore, a multi-centre, international observational study is necessary. Given the specific target population this study is not feasible in a single-centre approach. The goal is to find up to 6 centres that anticipate including 3 to 4 patients in the study within a time frame of one year.

Included patients should receive at least 6 doses of linezolid. Linezolid must be administered intravenously (iv) over a one hour controlled infusion (with use of a volumetric infusion pump).

Study Overview

• Status: Completed
• Conditions: Pneumonia
• Intervention / Treatment: Drug: Linezolid

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Ghent University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• BMI >35

• Radiographically and clinically documented pneumonia and one of the following:

  • the patient is MRSA screen-positive and is as such at high risk for MRSA pneumonia (MIC for linezolid is known or possible to assess)
  • the patient has a baseline respiratory tract sample positive for MRSA; MRSA pneumonia is likely
  • empiric therapy without linezolid is initiated (no obvious indication for MRSA involvement), but the patient is switch to linezolid therapy once culture results demonstrate MRSA as pathogen. CAVE: the patients must be included in the study prior to the moment the first trough sample must be drawn. As such, patients becoming MRSA-positive after >1 dose of linezolid cannot be included in the study.
• Decision to start treatment with linezolid for at least 3 days (6 doses of 600 mg).
• Patient is colonized or infected with MRSA (at any site) and it must be possible to sent a fresh isolate to the central laboratory for microbiology.
• Written informed consent by the patient or his/her legal representative.

Exclusion:

Contraindications as described in the summary of product characteristics (SPC).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Linezolid	Drug: Linezolid; 600 mg linezolid as a 1 hour controlled infusion (acceptable time frame is between 30 and 120 minutes), twice, at least 3 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics/-dynamics of linezolid in blood samples: T>MIC of 100.	A total of 17 blood samples will be collected over 72 hours after the first administration of linezolid, using a catheter. There will be evaluation of the proportion of patients who attain a T>MIC (Minimum Inhibitory Concentration) of 100% and the time frame in which they do so. The investigators therefore plan to measure unbound linezolid trough concentrations before administration of the second, third, fourth and fifth dose. Furthermore, the investigators will assess the AUC0 - 24h/MIC in all study subjects. Therefore, multiple plasma samples will be drawn after the fourth or fifth dose, when steady state conditions are reached	Over the course of 72 hours after the first administration of linezolid.
Pharmacokinetics/-dynamics of linezolid in urine samples.	This collection will be done using a catheter that was already in place, or will be collected in containers if no catheter is present at the time of this collection.	During 12 hours after 6th or 7th administration of linezolid.

Collaborators and Investigators

• Sponsor: University Ghent
• Collaborators: Pfizer; University Hospital, Ghent
• Investigators: Principal Investigator: Dirk Vogelaers, Ph.D., M.D., University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2013
• Primary Completion (Actual): September 30, 2016
• Study Completion (Actual): September 30, 2016

Study Registration Dates

• First Submitted: February 27, 2013
• First Submitted That Met QC Criteria: March 4, 2013
• First Posted (Estimate): March 6, 2013

Study Record Updates

• Last Update Posted (Actual): December 1, 2021
• Last Update Submitted That Met QC Criteria: November 18, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: pneumonia
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Linezolid
• Other Study ID Numbers: 2012/788; 2012-005127-33 (EudraCT Number)