Target Attainment and Pharmacokinetics of Antimicrobials in Non-critically Ill Surgery Patients (TAPAS) (TAPAS)

Target Attainment and Pharmacokinetics of Antimicrobials in Non-critically Ill Surgery Patients

In this prospective observational study, the investigators want to document pharmacokinetic/pharmacodynamic (PK/PD) target attainment of frequently used antimicrobials in an adult non critically ill surgery population (abdominal surgery, traumatology and septic orthopedic surgery). Furthermore, the investigators want to identify risk factors for not attaining predefined PK/PD targets.

The antibiotics of interest are amoxicillin(-clavulanic acid), flucloxacillin, piperacillin-tazobactam, meropenem and clindamycin.

Study Overview

• Status: Unknown
• Conditions: Surgery
• Intervention / Treatment: Drug: amoxicillin-clavulanic acid

Detailed Description

In this research proposal, the primary objective is to describe PK parameters (area under the curve (AUC), clearance (Cl), distribution volume (Vd) and half life (T1/2)) for the antibiotics of interest (amoxicillin(-(clavulanic acid), flucloxacillin, piperacillin-tazobactam, meropenem and clindamycin) for this adult non critically ill surgery population.

Besides, the investigators want to document pharmacokinetic/pharmacodynamic (PK/PD) target attainment of frequently used ABs in this population and to identify risk factors, for example augmented renal clearance (ARC), for not attaining predefined PK/PD targets.

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

• Study Contact: Name: Peter Declercq, PharmD; Phone Number: 003216342340; Email: peter.declercq@uzleuven.be
• Study Contact Backup: Name: Isabel Spriet, PhD; Phone Number: 003216341261; Email: isabel.spriet@uzleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • University Hospitals Leuven
    • Contact: Peter Declercq, PharmD.; Phone Number: +321642340; Email: peter.declercq@uzleuven.be
    • Principal Investigator: Peter Declercq, PharmD.

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

adult non-critically ill surgery patient admitted at the abdominal, trauma or septic orthopaedic surgery wards from the University Hospitals Leuven

Description

Inclusion Criteria:

Every adult non-critically ill surgery patient admitted at the abdominal, trauma or septic orthopaedic surgery wards from the University Hospitals Leuven treated with multiple doses of one of the antimicrobials of interest (i.e. intravenous (IV) amoxicillin(-clavulanic acid), flucloxacillin, piperacillin-tazobactam, meropenem, oral or IV clindamycin) is eligible for inclusion.

Exclusion Criteria:

• age ≤ 18 years
• treatment restrictions corresponding to a Do Not Reanimate code
• pregnancy
• lactation
• renal replacement therapy
• planned discharge or surgery in the coming antimicrobial dosing interval making sampling impossible

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The % of time that free concentrations of antimicrobials are above minimal inhibitory concentrations (MIC) or antimicrobial European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints	Per antimicrobial of interest, we will determine the % of time that free concentrations are above minimal inhibitory concentrations (MIC) or antimicrobial EUCAST breakpoints	During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve (AUC)	Per antimicrobial of interest, we will determine the pharmacokinetic parameter the area under the plasma concentration versus time curve (AUC).	During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial.
Clearance (Cl)	Per antimicrobial of interest, we will determine the pharmacokinetic parameter clearance (Cl).	During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial.
Volume of distribution (Vd)	Per antimicrobial of interest, we will determine the pharmacokinetic parameter the volume of distribution (Vd).	During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial.
Half life (T1/2)	Per antimicrobial of interest, we will determine the pharmacokinetic parameter the half life (T1/2).	During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial.
Risk factors for target non attainment	Multivariate analysis will be performed with target attainment as outcome. This will allow to identify risk factors for target non attainment.	During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial.

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Peter Declercq, PharmD, Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2016
• Primary Completion (Anticipated): September 30, 2018
• Study Completion (Anticipated): September 30, 2018

Study Registration Dates

• First Submitted: April 4, 2017
• First Submitted That Met QC Criteria: April 14, 2017
• First Posted (Actual): April 19, 2017

Study Record Updates

• Last Update Posted (Actual): April 20, 2017
• Last Update Submitted That Met QC Criteria: April 19, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: pharmacokinetics; antimicrobials; augmented renal clearance; non critically ill
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; beta-Lactamase Inhibitors; Clindamycin; Amoxicillin; Meropenem; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination; Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination
• Other Study ID Numbers: S59726

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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