Target-controlled Infusion Model for Cefepime

Study Overview
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Brief Summary
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For this study, a previously developed population pharmacokinetic (popPK) model for cefepime (Jonckheere et al., submitted to JAC) was programmed in Rugloop vII, which is a software program to drive an infusion pump. By entering patient data (such as gender, serum creatinine, age and weight) in Rugloop II, a patient-specific dose will be calculated and given to the patient. This concept is known as Target Controlled Infusion (TCI). The aim of this study is to prospectively validate the popPK model using TCI.

Official Title
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A Study to Evaluate the Predictive Performance of a Target-controlled Infusion Model for the Administration of Cefepime to Intensive Care Patients

Conditions
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Antimicrobial Treatment

Intervention / Treatment
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* Other: TCI group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients of 18 years of age or older, admitted to the hospital ICU and requiring administration of cefepime as part of their treatment Patients within the weight range of 50 -120kg Patients with calculated creatinine clearance within the range 15 to > 90 ml/min, allocated to one of three groups as described above. Written informed consent, or if not possible surrogate consent, or if not possible declaration for inclusion in an emergency, patient informed consent being signed as soon as possible. Patient with an arterial catheter in place for other reason than the current study purpose Exclusion Criteria: Patients displaying acute or chronic renal failure requiring renal replacement therapy Pregnancy Moribund patients Known sensitivity or allergy to cefepime Inclusion in another study involving antimicrobial treatment. Patient participating in a research for which a period of exclusion is currently required by other study protocol, ethical committee or health authority. Patient already previously included in the trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TCI group<br>Patients who receive cefepime based on TCI for a maximum of 5 days with a target concentration of cefepime of 16 mg/L. | Other: TCI group<br>* Drug: cefepime, Device: Target Controlled Infusion pump connected to Rugloop vII software<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Absolute Preditive Error (MdAPE, %) of predicted versus measured cefepime plasma concentrations (mg/L) |  | During the first 5 days of cefepime therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with Neurotoxicity related to cefepime based on Naranjo criteria |  | Evaluation during the first 5 days of cefepime therapy | 
| Negativation of microbiological cultures | When applicable, evaluation of semi-quantitative culture of clinical samples (e.g. respiratory samples). This is not mandatory for study inclusion. | Evaluation during the first 5 days of cefepime therapy | 
| Percentage of patients with clinical cure | Clinical cure when all criteria are met: Patient not deceased WBC count between 4000/µL and 11000/µL OR decreased by 25% relative to peak value CRP decrease of 50% relative to peak value If respiratory infection: i) absence or decrease in sputa/tracheal secretions; ii) extubated and not re-intubated within 24h after cessation of cefepime (if relevant) Body temperature between 35°C and 38°C | At the end of the study (maximum 5 days after inclusion) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Target Controlled Infusion, Pharmacokinetics, Cefepime, critically ill patients