Pharmacokinetic and Pharmacodynamic Evaluation of Linezolid Administered Intravenously in MRSA-positive, Morbidly Obese Patients With Pneumonia (UGENT_LIMOP)
Primary Purpose
Pneumonia
Status
Completed
Phase
Phase 4
Locations
Belgium
Study Type
Interventional
Intervention
Linezolid
Sponsored by
About this trial
This is an interventional other trial for Pneumonia focused on measuring pneumonia
Eligibility Criteria
- 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).
Sites / Locations
- Ghent University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Linezolid
Arm Description
Outcomes
Primary Outcome Measures
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
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT01805284
First Posted
February 27, 2013
Last Updated
November 18, 2021
Sponsor
University Ghent
Collaborators
University Hospital, Ghent, Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT01805284
Brief Title
Pharmacokinetic and Pharmacodynamic Evaluation of Linezolid Administered Intravenously in MRSA-positive, Morbidly Obese Patients With Pneumonia
Acronym
UGENT_LIMOP
Official Title
Pharmacokinetic and Pharmacodynamic Evaluation of Linezolid Administered Intravenously in MRSA-positive, Morbidly Obese Patients With Pneumonia
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
February 2013 (Actual)
Primary Completion Date
September 30, 2016 (Actual)
Study Completion Date
September 30, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Ghent
Collaborators
University Hospital, Ghent, Pfizer
4. Oversight
Data Monitoring Committee
No
5. 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pneumonia
Keywords
pneumonia
7. Study Design
Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Linezolid
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Linezolid
Intervention Description
600 mg linezolid as a 1 hour controlled infusion (acceptable time frame is between 30 and 120 minutes), twice, at least 3 days.
Primary Outcome Measure Information:
Title
Pharmacokinetics/-dynamics of linezolid in blood samples: T>MIC of 100.
Description
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
Time Frame
Over the course of 72 hours after the first administration of linezolid.
Title
Pharmacokinetics/-dynamics of linezolid in urine samples.
Description
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.
Time Frame
During 12 hours after 6th or 7th administration of linezolid.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dirk Vogelaers, Ph.D., M.D.
Organizational Affiliation
University Hospital, Ghent
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ghent University Hospital
City
Ghent
ZIP/Postal Code
9000
Country
Belgium
12. IPD Sharing Statement
Learn more about this trial
Pharmacokinetic and Pharmacodynamic Evaluation of Linezolid Administered Intravenously in MRSA-positive, Morbidly Obese Patients With Pneumonia
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