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

Completed

• Conditions: Drug Mechanism

• Registration Number: NCT02458261
• Lead Sponsor: University of Cincinnati

Brief Summary

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

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 Timeline

• Study Start: 2015-03
• Study First Submitted: 2015-04-27
• Study First Submitted QC: 2015-05-27
• Study First Posted: 2015-06-01
• Primary Completion: 2018-12
• Study Completion: 2019-02
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-15
• Last Update Posted: 2019-04-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Composite pharmacokinetic and pharmacodynamic profile of extended-infusion cefepime in CRRT	up to 12 months	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.