Pharmacokinetics of Piperacillin and Tazobactam in Critically Ill Patients

Bacterial Infections Clinical Trial

— PICTAR  

Official title:

Pharmacokinetics of Piperacillin and Tazobactam in Critically Ill Patients - Finding the Best Predictor for Piperacillin-tazobactam Clearance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03738683
• Other study ID #: UMCN-AKF 18.11
• Status: Completed
• Start date: February 1, 2019
• Est. completion date: October 1, 2019

Study information

• Verified date: September 2019
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: October 1, 2019
• Est. primary completion date: September 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Exclusion Criteria:

1. Has previously participated in this trial.

2. Is on renal replacement therapy.

Related Conditions & MeSH terms

• Bacterial Infections

Intervention

Drug:
• Piperacillin/tazobactam
Dose according to summary of product characteristics (SPC) or local protocols

Locations

Country	Name	City	State
Netherlands	Radboud University Medical Center	Nijmegen	Gelderland
Netherlands	University Medical Centre Utrecht	Utrecht

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	UMC Utrecht

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total drug clearance	Pharmacokinetic curves will be taken	1 day
Secondary	Volume of distribution	Pharmacokinetic curves will be taken	1 day
Secondary	Area under the curve	Pharmacokinetic curves will be taken	1 day