Pharmacokinetics of Amikacin and Cefuroxime in Critically Ill Patients. (PHARAOH)

Population Pharmacokinetics of Amikacin and Cefuroxime in Critically Ill Septic Patients Admitted to the ICU or the ED

Infections in critically ill patients are a major healthcare problem and an important source of morbidity and mortality. Since critically ill patients often have altered pharmacokinetics (PK) compared to non-critically ill patients there is a substantial risk that present standard dosing regimens of antibiotics lead to suboptimal outcomes for patients on the ICU or the ED. To prevent the risk of inadequate dosing in ICU patients, it is important to fully understand the PK of antibiotics in this vulnerable group in order to optimize the dosing regimens.

With this study, the investigators will describe the pharmacokinetics of cefuroxime and amikacin in ICU and ED patients. A heterogeneous population of ICU and ED patients will be included to be able to find which factors might influence the pharmacokinetics of these drugs and to what extent. By using population modeling the investigators will simulate different dosing regimens and MIC values and compare probability of target attainment between each of these dose and MIC combinations. This will allow the investigators to optimize dosing regimens of cefuroxime and amikacin in critically ill patients.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Septic Shock; Critically Ill; Infection, Bacterial
• Intervention / Treatment: Drug: Cefuroxime; Drug: Amikacin

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Julian Machiels, MD, MSc; Phone Number: +31243614369; Email: julian.machiels@radboudumc.nl

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Recruiting
    • Radboudumc intensive care
    • Contact: J Machiels

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 admitted to the ICU or ED.

Description

Inclusion Criteria:

1. The patient is admitted to the ICU or ED;
2. The patient is at least 18 years of age on the day of inclusion;
3. Is managed with a central venous catheter or arterial line;
4. Is treated with amikacin and/or cefuroxime as standard care.

Exclusion Criteria:

1. Has previously participated in this study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cefuroxime/Amikacin; 20 patients will be included in the cefuroxime cohort and 20 patients in the amikacin cohort.	Drug: Cefuroxime; Patients receive cefuroxime as part of standard care.; Drug: Amikacin; Patients receive amikacin as part of standard care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To describe the population pharmacokinetics of amikacin in Intensive Care or Emergency Department patients	1 year
To describe the population pharmacokinetics of cefuroxime in Intensive Care or Emergency Department patients	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the influence of renal clearance and weight on the pharmacokinetics of amikacin and cefuroxime	1 year
To determine the proportion of patients who attain adequate PK/PD targets in relation to the MIC of the suspected pathogen.	1 year
To determine the toxicity of amikacin	1 year

Other Outcome Measures

Outcome Measure	Time Frame
To investigate to what extend renal replacement therapy affects the pharmacokinetics of amikacin and cefuroxime	1 year

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Roger Brüggemann, PhD, Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2020
• Primary Completion (Anticipated): December 15, 2023
• Study Completion (Anticipated): December 15, 2023

Study Registration Dates

• First Submitted: July 9, 2020
• First Submitted That Met QC Criteria: July 9, 2020
• First Posted (Actual): July 14, 2020

Study Record Updates

• Last Update Posted (Actual): September 10, 2022
• Last Update Submitted That Met QC Criteria: September 9, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Infection; Septic Shock; Sepsis; Critically Ill
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Bacterial Infections and Mycoses; Shock; Sepsis; Shock, Septic; Critical Illness; Bacterial Infections; Anti-Infective Agents; Anti-Bacterial Agents; Amikacin; Cefuroxime; Cefuroxime axetil
• Other Study ID Numbers: PHARAOH

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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