Ceftaroline Pharmacokinetics in Continuous Renal Replacement Therapy

Ceftaroline Pharmacokinetics in Critically Ill Patients Receiving Continuous Renal Replacement Therapy

Dosing of ceftaroline in patients with chronic kidney disease is defined, but there is no data on pharmacokinetics and pharmacodynamics of the drug in patients receiving continuous renal replacement therapy (CRRT). The purpose of this study is to determine pharmacokinetics and pharmacodynamics of ceftaroline in a critically ill patient population receiving CRRT, in order to define a dosing recommendation in this population.

Study Overview

• Status: Completed
• Conditions: Critically Ill; Infection During Renal Replacement Therapy
• Intervention / Treatment: Other: Ceftaroline levels in CRRT

Detailed Description

Ceftaroline fosamil is a time-dependent, hydrophilic, bactericidal fifth generation cephalosporin that was FDA approved in 2010 for community acquired pneumonia and skin and skin structure infections. Ceftaroline is FDA approved for both Gram-positive and Gram-negative organisms. Gram-positive organisms covered are Staphylococcus aureus (methicillin resistant and methicillin sensitive strains), Streptococcus agalactiae, Streptococcus pneumonia, and Streptococcus pyogenes. Gram-negative coverage includes Escherichia coli, Haemophilus influenza, Klebsiella pneumonia, and Klebsiella oxytoca. In order for ceftaroline to exhibit effective bacterial killing, it requires that a certain percentage of the dosing interval is spent above the MIC.

Dosing of ceftaroline in patients with chronic kidney disease is defined, but there is no data on pharmacokinetics and pharmacodynamics of the drug in patients receiving continuous renal replacement therapy (CRRT). The purpose of this study is to determine pharmacokinetics and pharmacodynamics of ceftaroline in a critically ill patient population receiving CRRT, in order to define a dosing recommendation in this population. CRRT modes that patients may be receiving in this trial include: continuous veno-venous hemofiltration (CVVH), continuous veno-venous hemodialysis (CVVHD), and continuous veno-venous hemodiafiltration (CVVHDF).

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Admitted to an intensive care unit
• Receiving CRRT (CVVH, CVVHDF, CVVHD)
• Receiving ceftaroline

Exclusion Criteria:

• Pregnant patients
• Burn patients
• Patients with toxic epidermal necrolysis or Stevens-Johnson syndrome
• Patients prescribed extended infusion ceftaroline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Ceftaroline in CRRT; Ceftaroline levels measured in patients receiving continuous renal replacement therapy	Other: Ceftaroline levels in CRRT; Levels of ceftaroline measured in patients receiving CRRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ceftaroline pharmacokinetics in critically ill patients receiving continuous renal replacement therapy - Half-life	Ceftaroline elimination half-life	1 year
Ceftaroline pharmacokinetics in critically ill patients receiving continuous renal replacement therapy - Clearance	Ceftaroline clearance	1 year
Ceftaroline pharmacokinetics in critically ill patients receiving continuous renal replacement therapy - Volume of distribution	Ceftaroline volume of distribution	1 year
Ceftaroline pharmacokinetics in critically ill patients receiving continuous renal replacement therapy - Sieving coefficient	Continuous renal replacement therapy modality sieving coefficient for ceftaroline	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ceftaroline pharmacodynamics in patients receiving continuous renal replacement therapy	Percentage of time ceftaroline levels are above the minimum inhibitory concentration for the most likely pathogen(s)	1 year

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Investigators: Principal Investigator: Mojdeh Heavner, University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 9, 2018
• Primary Completion (ACTUAL): September 1, 2020
• Study Completion (ACTUAL): September 1, 2020

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: November 1, 2019
• First Posted (ACTUAL): November 5, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 18, 2021
• Last Update Submitted That Met QC Criteria: March 17, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Critical Illness; Anti-Infective Agents; Anti-Bacterial Agents; Ceftaroline fosamil
• Other Study ID Numbers: HP-00077498

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes