Target-controlled Infusion Model for Cefepime

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

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.

Study Overview

• Status: Completed
• Conditions: Antimicrobial Treatment
• Intervention / Treatment: Other: TCI group

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TCI group; 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; Drug: cefepime, Device: Target Controlled Infusion pump connected to Rugloop vII software

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: Onze Lieve Vrouw Hospital
• Collaborators: University Medical Center Groningen; University Ghent

Publications and helpful links

General Publications

• Jonckheere S, De Neve N, Verbeke J, De Decker K, Brandt I, Boel A, Van Bocxlaer J, Struys MMRF, Colin PJ. Target-Controlled Infusion of Cefepime in Critically Ill Patients. Antimicrob Agents Chemother. 2019 Dec 20;64(1):e01552-19. doi: 10.1128/AAC.01552-19. Print 2019 Dec 20.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): March 1, 2018
• Study Completion (Actual): February 28, 2019

Study Registration Dates

• First Submitted: February 6, 2016
• First Submitted That Met QC Criteria: February 17, 2016
• First Posted (Estimate): February 23, 2016

Study Record Updates

• Last Update Posted (Actual): March 1, 2019
• Last Update Submitted That Met QC Criteria: February 28, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Pharmacokinetics; critically ill patients; Cefepime; Target Controlled Infusion
• Other Study ID Numbers: 2016/005