Clinical trial NCT01805284: Pharmacokinetic and Pharmacodynamic Evaluation of Linezolid Administered Intravenously in MRSA-positive, Morbidly Obese Patients With Pneumonia
Official title: Pharmacokinetic and Pharmacodynamic Evaluation of Linezolid Administered Intravenously in MRSA-positive, Morbidly Obese Patients With Pneumonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pneumonia
Keywords: pneumonia
Lead sponsor: University Ghent
Sponsor class: OTHER
Collaborators: name: University Hospital, Ghent
name: Pfizer
First posted: 2013-03-06
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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).


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).

Primary outcomes:
measure: Pharmacokinetics/-dynamics of linezolid in blood samples: T>MIC of 100.
timeFrame: Over the course of 72 hours after the first administration of linezolid.
measure: Pharmacokinetics/-dynamics of linezolid in urine samples.
timeFrame: During 12 hours after 6th or 7th administration of linezolid.
Secondary outcomes:
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Ghent University Hospital
Study officials:
affiliation: University Hospital, Ghent
name: Dirk Vogelaers, Ph.D., M.D.
role: PRINCIPAL_INVESTIGATOR
References: