Piperacillin Pharmacokinetics in ICU Patients

Sepsis Clinical Trial

Official title:

Piperacillin Pharmacokinetics in Intensive Care Unit Patients Following Standard Treatment With Intermittent and Continuous Infusion

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02478073
• Other study ID #: AB-ICU
• Status: Recruiting
• Phase: N/A
• First received: June 15, 2015
• Last updated: June 17, 2015
• Start date: June 2015
• Est. completion date: May 2016

Study information

• Verified date: June 2015
• Source: University of Aarhus
• Contact: Kristina Öbrink-Hansen, MD
• Phone: +45 78452845
• Email: krisoebr[@]rm.dk
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection Agency
• Study type: Observational

Clinical Trial Summary

Antibiotic dosing in critically ill patients poses a challenge for clinicians due to the pharmacokinetic changes seen in this population. Piperacillin/tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality.

Patients in the Intensive Care Unit (ICU), treated with piperacillin/tazobactam, had their plasma concentration of piperacillin determined 1-3 times weekly. Patients received piperacillin as intermittent bolus infusion 3 times daily or as continuous infusion (this was up to the treating physician). Time above the minimal inhibitory concentration (T>MIC) estimated for each patient was evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/L). Pharmacokinetic-pharmacodynamic (PK-PD) targets evaluated were 100% f T>MIC (free piperacillin concentration maintained above the MIC throughout the dosing interval) and 50% fT>4xMIC (free piperacillin concentration maintained at a level fourfold the MIC for at least 50% of the dosing interval).

Description:

Early appropriate antimicrobial therapy is of utmost importance for reducing mortality in critically ill patients with sepsis and septic shock. Pathophysiological changes associated with the septic process, such as changes in volume of distribution (Vd), drug clearance (CL), decrease in plasma-protein concentration and organ dysfunction, lead to pharmacokinetic (PK) changes that may alter the efficacy of the antimicrobial given. As a consequence, antibiotic plasma concentrations are variable and hard to predict in these patients, which makes optimal antibiotic exposure a challenge, especially in the early phase of treatment.

Piperacillin/tazobactam is a β-lactam - β-lactamase inhibitor combination frequently used for empirical treatment in the critically ill. It is a time-dependent antibiotic where antibacterial activity is related to the time for which the free, unbound concentration of the drug is maintained above the minimal inhibitory concentration (f T>MIC). Maximizing f T>MIC both increases the therapeutic impact and reduces the risk of drug resistance development. Because of the PK changes seen in the critically ill, standard dosing of antimicrobials may result in subtherapeutic plasma-concentrations and it has been suggested that current empiric dosing recommendations for Intensive Care Unit (ICU) patients are inadequate and needs to be reconsidered.

Piperacillin/tazobactam is generally administered either as 4g/0.5g every 8 hour (h) or as 12g given continuously over 24 hours.The aim of this study is to determine if this dosing results in therapeutic plasma concentrations in septic patients. Patients treated with piperacillin/tazobactam given as intermittent bolus infusion had piperacillin plasma concentrations determined once a week. Patients treated with piperacillin/tazobactam given as continuous infusion had piperacillin plasma concentrations determined three times a week. Time above the minimal inhibitory concentration (T>MIC) estimated for each patient was evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/L). Pharmacokinetic-pharmacodynamic (PK-PD) targets evaluated were 100% f T>MIC (free piperacillin concentration maintained above the MIC throughout the dosing interval) and 50% fT>4xMIC (free piperacillin concentration maintained at a level fourfold the MIC for at least 50% of the dosing interval).

The unbound piperacillin plasma concentrations were determined using ultra high performance liquid chromatography (UPLC). There was no intervention in the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Sepsis or septic shock

• Treatment with piperacillin/tazobactam

Exclusion Criteria:

• Age under 18 years

• Renal replacement therapy

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Sepsis
• Septic Shock

Locations

Country	Name	City	State
Denmark	Aarhus Univbersity Hospital, Department of Anesthesia and Intensive Care Medicine	Aarhus N

Sponsors (1)

Lead Sponsor	Collaborator
Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood-plasma concentration of Piperacillin	Blood-plasma concentration of Piperacillin will be performed through ultra high performance liquid chromatography (UPLC). The concentrations will be compared to the clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/L).	A blood-test will be drawn 1-3 times weekly. Participants will be followed for the duration of piperacillin/tazobactam treatment, an expected average time of two weeks.	No
Secondary	Percentage of time above the minimal inhibitory concentration (T>MIC)	The blood-plasma concentrations will be used to determine the percentage of time, within the dosing interval, that the blood-plasma concentration is at a level above the minimal inhibitory concentration (T>MIC)	A blood-test will be drawn 1-3 times weekly. Participants will be followed for the duration of piperacillin/tazobactam treatment, an expected average time of two weeks.	No