Pharmacokinetics and Pharmacodynamics of Extended-Infusion Cefepime in Continuous Renal Replacement Therapy

This prospective, multi-center study aims to determine the pharmacokinetics and pharmacodynamics of extended-infusion cefepime in continuous renal replacement therapy (CRRT).

Study Overview

• Status: Completed
• Conditions: Drug Mechanism

Detailed Description

This prospective, multi-center study aims to determine the pharmacokinetics and pharmacodynamics of extended-infusion cefepime in CRRT. Patients on CRRT who are being initiated on cefepime 2000 mg IV every eight hours with a four-hour infusion will be considered for enrollment. Pre- and post-membrane serum levels will be drawn at scheduled intervals for both the first dose and again during another dose at steady state. Concomitant effluent and urine levels will also be obtained. A pharmacokinetic analysis will be performed and Monte Carlo simulations will be used to determine the probability of target attainment for various pharmacodynamic endpoints. Documented organism MICs will be used to determine the cumulative fraction of response.

• Study Type: Observational
• Enrollment (Actual): 10

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Critically ill patients on continuous renal replacement therapy who are being initiated on cefepime 2000 mg IV every 8 hours with a four-hour infusion

Description

Inclusion Criteria:

• Age ≥ 18 years
• Admission to medical intensive care unit (MICU), surgical intensive care unit (SICU), neuroscience intensive care unit (NSICU), or cardiovascular intensive care unit (CVICU), at the University of Cincinnati Medical Center, or the mixed ICU at West Chester Hospital
• Patients receiving continuous venovenous hemofiltration or continuous venovenous hemodialysis
• Receiving empiric or definitive cefepime 2 g IV every 8 hours with a four-hour infusion

Exclusion Criteria:

• Prisoners
• Pregnant women
• Patients with cystic fibrosis
• Burns patients
• 24-hour urine output > 400 mL or unknown

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite pharmacokinetic and pharmacodynamic profile of extended-infusion cefepime in CRRT	Each patient will have samples collected on both the first dose and another dose at presumed steady state (dose four, five, or six) to determine the pharmacokinetic and pharmacodynamic profile of extended-infusion cefepime in CRRT. Pharmacokinetic outcomes calculated include half life, volume of distribution, and area under the plasma concentration versus time curve. Sieving and saturation coefficients will also be calculated as appropriate. Time above the minimum inhibitory concentration will be the primary pharmacodynamic outcome studied.	up to 12 months

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Collaborators: Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): February 1, 2019

Study Registration Dates

• First Submitted: April 27, 2015
• First Submitted That Met QC Criteria: May 27, 2015
• First Posted (Estimate): June 1, 2015

Study Record Updates

• Last Update Posted (Actual): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 15, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 2014-6119

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED