Pharmacokinetics of Teicoplanin in Intensive Care and Haematology Patients (PLATO)

A Population PK Study Into Teicoplanin in Intensive Care and Haematology Patients - a Strategy Towards Model Informed Precision Dosing

Characterize teicoplanin PK in critically ill patients with a specific focus on alterations of exposure due to variability in renal function.

In a prospective, observational, open-label study the investigators aim to define PK of free drug concentrations of teicoplanine in ICU and heamatology patients and define a PK model for Bayesian dose individualization.

Study Overview

• Status: Completed
• Conditions: Bacterial Infections
• Intervention / Treatment: Other: No intervention

Detailed Description

Bacterial infection with coagulase-negative staphylococci (CNS) or methicillin resistant and sensitive staphylococcus aureus(MRSA/MSSA) indicates poor prognosis and increased mortality in critically ill patients.

With the current emergence of glycopeptide-intermediate sensitive Staphylococcus aureus strains, personalized dosing of teicoplanin is of utmost importance to preserve the current therapeutic armamentarium.

Teicoplanin is considered equipotent to vancomycin, albeit safer with minimal nephrotoxicity. It is estimated that 50% of all critically ill patients treated with teicoplanin does not reach target exposure. This is the major driver for treatment failure and development of resistance and dose individualization will overcome this problem.

Our project is aimed at developing and implementing a personalized dosing strategy for teicoplanin, to prevent development of glycopeptide resistance and allow safe treatment of glycopeptide intermediate sensitive bacteria.

In a prospective clinical study, critically ill patients (defined as ICU and hematology patients) who receive teicoplanin as standard care for antimicrobial treatment will be eligible for inclusion. Minimally invasive blood sampling for pharmacokinetic analysis will be retrieved through an indwelling central venous catheter or an arterial line (9 samples per patient). Teicoplanin total and free drug concentrations will be measured using a validated analytical assay. A total of 30 patients will be included.

We will develop a population PK model using nonlinear mixed effects modelling for total and unbound teicoplanin to characterize the magnitude of inter-individual variability in PK parameters (clearance, distribution volume), and to identify patient-derived characteristics that can predict such variability in a critically ill patient population.

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands
      • Radboud University 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

• Sampling Method: Non-Probability Sample

Study Population

All critically ill patients (defined as ICU and hematology patients) with a suspected or proven bacterial infection who are already treated with teicoplanin as a part of routine clinical care are eligible for inclusion. A total of 30 patients will be included.

Description

Inclusion Criteria:

1. The patient is admitted to the ICU of the haematology department
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 teicoplanin as a part of standard care

Exclusion Criteria:

1. Has previously participated in this study
2. Patient is admitted to the haematology department and receives any form of RRT other than continuous venovenous hemofiltration (CVVH).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total drug clearance	Pharmacokinetic curves will be taken	4 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volume of distribution	Pharmacokinetic curves will be taken	4 days
Area under the curve	Pharmacokinetic curves will be taken	4 days

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 15, 2020
• Primary Completion (ACTUAL): October 19, 2021
• Study Completion (ACTUAL): December 1, 2022

Study Registration Dates

• First Submitted: September 18, 2019
• First Submitted That Met QC Criteria: September 18, 2019
• First Posted (ACTUAL): September 19, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 31, 2023
• Last Update Submitted That Met QC Criteria: January 30, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Critically ill; Teicoplanin
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections
• Other Study ID Numbers: UMCN-AKF 19.05

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