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

Sponsor

University Ghent (Other)

Overall Status

Completed

CT.gov ID

NCT01805284

Collaborator

University Hospital, Ghent (Other), Pfizer (Industry)

Enrollment

Location

Arm

43.9

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Pneumonia	Drug: Linezolid	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

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

Actual Study Start Date :

Feb 1, 2013

Actual Primary Completion Date :

Sep 30, 2016

Actual Study Completion Date :

Sep 30, 2016

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Pharmacokinetics/-dynamics of linezolid in blood samples: T>MIC of 100. [Over the course of 72 hours after the first administration of linezolid.]
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
Pharmacokinetics/-dynamics of linezolid in urine samples. [During 12 hours after 6th or 7th administration of linezolid.]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ghent University Hospital	Ghent		Belgium	9000

Sponsors and Collaborators

University Ghent
University Hospital, Ghent
Pfizer

Investigators

Principal Investigator: Dirk Vogelaers, Ph.D., M.D., University Hospital, Ghent

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University Ghent

ClinicalTrials.gov Identifier:

NCT01805284

Other Study ID Numbers:

2012/788
2012-005127-33

First Posted:

Mar 6, 2013

Last Update Posted:

Dec 1, 2021

Last Verified:

Nov 1, 2021

Keywords provided by University Ghent

pneumonia

Additional relevant MeSH terms:

Pneumonia

Linezolid

Study Results

No Results Posted as of Dec 1, 2021