Official Title: “Pharmacokinetics Variability of Ceftriaxone in Septic ICU Patients”

Ceftriaxone pharmacokinetics variability in intensive care unit septic patients

In intensive care units, drug dosage is often based on study made on healthy volunteers or on less severe patients.

However, pharmacokinetic alterations have been described for some drugs used in intensive care units.

These alterations, consequences of alteration of volume of distribution, of protein concentrations, of impaired hepatic and renal functions can result in accumulation with toxicity or « under dosage » with inefficacity.

Ceftriaxone is an antibiotic often prescribed in intensive care unit. However, despite this large utilisation, very few data is available on the pharmacokinetic in intensive care unit, and optimal dosage is not known.

Our objective is to develop a population pharmacokinetics model of ceftriaxone in intensive care unit patients with sepsis, severe sepsis and septic shock and to identify the « data » explaining interindividual variability of each pharmacokinetics parameter.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics/Dynamics Study

This is a one centre population pharmacokinetics non interventional study. One group of 50 patients allows the development of the model and a second group of 20 patients will be used for the validation of the model.

Septic patients treated with ceftriaxone according to standard procedure of our ICU could be included before the second administration of the drug. In the development group, patients will underwent five determination of serum concentration of ceftriaxone during the 24 hours following the second administration. The timing of samples will be randomised in three groups. A second phase of sampling will take place during the fifth day of ceftriaxone therapy for sepsis and severe sepsis patients and after 48 hours catecholamine- free for septic shock patients.

For the validation group, ten samples will be obtained at the same periods. This study will not induce any change in the care of patients.

Samples will be centrifugated immediately after collection and conserved at - 20 °C.

Ceftriaxone will be assayed in the department of pharmacology, university of Marseille France, usig HPLC method.

Pharmacokinetic analysis will used NONlinear Mixed Effects Modelling logiciel

Intervention(s) in this Clinical Trial

• Drug: ceftriaxone

Primary Measures

• serum drug concentration
• pharmacokinetics parameter (plasmatic half-life, clearance, ...)
• ratio of serum drug concentration on MCI

Inclusion Criteria:

• Eighteen-year or more
• sepsis, severe sepsis or septic shock (according to Bone's criteria)
• admission to intensive care unit
• informed consent obtained
• affiliation to medicare

Exclusion Criteria:

• Previous haemodialysis
• hemopathy
• known allergy to cephalosporin
• patients whose death is considered imminent

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Association Pour La Promotion A Tours De La Reanimation Medicale

Overall Clinical Trial Officials and Contacts

DENIS GAROT, MD Principal Investigator chru tours  

Overall Contact: DENIS GAROT, MD +33 2 47 47 38 55 garot@med.univ-tours.fr

Information obtained from ClinicalTrials.gov on November 20, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00449800

Study ID Number: APTRM 2006-02

ClinicalTrials.gov Identifier: NCT00449800

Health Authority: France: Afssaps - French Health Products Safety Agency