Pharmacokinetics of Piperacillin and Tazobactam in Critically Ill Patients

Completed

• Conditions: Bacterial Infections

• Registration Number: NCT03738683
• Lead Sponsor: Radboud University Medical Center

Brief Summary

Optimal understanding of piperacillin-tazobactam pharmacokinetics in critically ill patients is lacking resulting in large variation of achieved exposure and possible inadequate therapy. The investigators hypothesize that drug dosing based on CKD-EPIcr-cys provides a useful method to individualize and optimize therapy for piperacillin-tazobactam and eventually improve outcome.

In a multi-centre, observational, open-label study the investigators aim to define PK of free drug concentrations of both piperacillin and tazobactam in ICU patients and define a PK model for estimation of renal function that most accurately predicts piperacillin and tazobactam clearance.

Detailed Description

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. To prevent the risk of inadequate dosing in ICU patients, it is important to fully understand the PK of antibiotics in this vulnerable group so that dosing regimens can be optimized.

Although PK of piperacillin has been well studied in healthy volunteers, non-critically ill patients and more recently the critically ill, there are still gaps of knowledge in the PK of piperacillin-tazobactam in ICU patients. Especially when focusing on the influence of renal function and on the PK of tazobactam.

Both piperacillin and tazobactam are excreted primarily by the kidneys via glomerular filtration and tubular secretion. Elimination half life of piperacillin-tazobactam increases with decreasing renal function. Substantial changes in renal function are common in ICU patients. Due to these changes PK targets are often not reached. This indicates the need to define the best predictor for piperacillin-tazobactam clearance in ICU patients in order to improve drug dosing. The use of combined filtration markers together, cystatin C and creatinine, can improve precision in estimating GFR (eGFR).

In a multi-centre, observational, open-label study the investigators aim to define PK of free drug concentrations of both piperacillin and tazobactam in ICU patients and define a PK model for estimation of renal function that most accurately predicts piperacillin and tazobactam clearance.

Patients will receive standard care, as stated in the product characteristics or according to local protocols. Minimally invasive blood sampling for pharmacokinetic analysis will be retrieved through a central venous catheter or an arterial line. Full pharmacokinetic curves will be taken for individual patients on the intermittent dosing regimen and limited sampling will be taken for individual patients on the continuous dosing regimen. A total of 40 patients will be included.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-10-22
• Study First Submitted QC: 2018-11-08
• Study First Posted: 2018-11-13
• Study Start: 2019-02-01
• Status Verified: 2019-09
• Primary Completion: 2019-09-01
• Study Completion: 2019-10-01
• Last Update Submitted: 2019-11-20
• Last Update Posted: 2019-11-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Patient is admitted to an ICU.
2. Subject is at least 18 years old on the day of the first dosing.
3. Is managed with a central venous catheter or arterial line.
4. Patient is treated with piperacillin/tazobactam.

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Exclusion Criteria

1. Has previously participated in this trial.
2. Is on renal replacement therapy.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Total drug clearance	1 day	Pharmacokinetic curves will be taken

Secondary Outcome Measures

Name	Time	Method
Volume of distribution	1 day	Pharmacokinetic curves will be taken
Area under the curve	1 day	Pharmacokinetic curves will be taken

Trial Locations

Locations (2)

University Medical Centre Utrecht; 🇳🇱 Utrecht, Netherlands

Radboud University Medical Center; 🇳🇱 Nijmegen, Gelderland, Netherlands