Clinical trial NCT03120663: Target Attainment and Pharmacokinetics of Antimicrobials in Non-critically Ill Surgery Patients (TAPAS)
Official title: Target Attainment and Pharmacokinetics of Antimicrobials in Non-critically Ill Surgery Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Surgery
Keywords: antimicrobials
pharmacokinetics
augmented renal clearance
non critically ill
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2017-04-19
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: The % of time that free concentrations of antimicrobials are above minimal inhibitory concentrations (MIC) or antimicrobial European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints
timeFrame: During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial.
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial.
measure: Clearance (Cl)
timeFrame: During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial.
measure: Volume of distribution (Vd)
timeFrame: During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial.
measure: Half life (T1/2)
timeFrame: During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial.
measure: Risk factors for target non attainment
timeFrame: During 1 dosing interval at steady state. This is at earliest 72h after initialization of the antimicrobial.
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospitals Leuven
Study officials:
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Peter Declercq, PharmD
role: PRINCIPAL_INVESTIGATOR
References: