Bacterial InfectionsPICTARNCT03738683
Pharmacokinetics of Piperacillin and Tazobactam in Critically Ill Patients
An observational study of Bacterial Infections, run by Radboud University Medical Center at 2 sites in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bacterial Infections
- What is being tested?
- Piperacillin/tazobactam
- How many people
- 40 participants
- Where
- 2 sitesNetherlands
- Study dates
- 1 Feb 2019to 1 Oct 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All critically ill patients with a suspected or proven bacterial infection who are already treated with piperacillin-tazobactam as a part of routine clinical care are eligible for inclusion. A total of 40 patients will be included: 30 patients receiving intermittent infusion of piperacillin-tazobactam and 10 patients receiving continuous infusion.
Who may be able to join
- Patient is admitted to an ICU.
- Subject is at least 18 years old on the day of the first dosing.
- Is managed with a central venous catheter or arterial line.
- Patient is treated with piperacillin/tazobactam.
Who cannot join
- Has previously participated in this trial.
- Is on renal replacement therapy.
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
Radboud University Medical Center
Nijmegen, Gelderland
University Medical Centre Utrecht
Utrecht
About this study
Official title: Pharmacokinetics of Piperacillin and Tazobactam in Critically Ill Patients - Finding the Best Predictor for Piperacillin-tazobactam Clearance
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.
Read the 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.
- Conditions
- Bacterial Infections
- Being tested
- Piperacillin/tazobactam
- Keywords
- Pharmacokinetics, Piperacillin-tazobactam, Renal function, Intensive Care Unit, Cystatin C
- Medical subject headings
- Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Piperacillin/tazobactamDrug
Dose according to summary of product characteristics (SPC) or local protocols
What is being measured
The primary outcome is the main question the study is designed to answer.
Total drug clearance
Pharmacokinetic curves will be taken
Measured: 1 day
Secondary outcomes (2)
Volume of distribution
Pharmacokinetic curves will be taken
Measured: 1 day
Area under the curve
Pharmacokinetic curves will be taken
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2018
- Study start1 Feb 2019
- Primary completion1 Sep 2019
- Study completion1 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bacterial InfectionsStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- UMC Utrecht
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03738683
- Sponsor's protocol ID
- UMCN-AKF 18.11
- Acronym
- PICTAR
- Status last verified
- Sep 2019
- First submitted
- 22 Oct 2018
- Last updated
- 21 Nov 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wallenburg E, Ter Heine R, Schouten JA, Raaijmakers J, Ten Oever J, Kolwijck E, Burger DM, Pickkers P, Frenzel T, Bruggemann RJM. An Integral Pharmacokinetic Analysis of Piperacillin and Tazobactam in Plasma and Urine in Critically Ill Patients. Clin Pharmacokinet. 2022 Jun;61(6):907-918. doi: 10.1007/s40262-022-01113-6. Epub 2022 Apr 4.
PubMed 35377133
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics of Piperacillin and Tazobactam in Critically Ill Patients - Finding the Best Predictor for Piperacillin-tazobactam Clearance
- ClinicalTrials.gov ID
- NCT03738683
- Acronym / sponsor ID
- PICTAR / UMCN-AKF 18.11
- Conditions
- Bacterial Infections
- Keywords
- Pharmacokinetics, Piperacillin-tazobactam, Renal function, Intensive Care Unit, Cystatin C
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- UMC Utrecht
- Study start
- 1 Feb 2019 (actual)
- Primary completion
- 1 Sep 2019 (actual)
- Study completion
- 1 Oct 2019 (actual)
- First posted
- 13 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All critically ill patients with a suspected or proven bacterial infection who are already treated with piperacillin-tazobactam as a part of routine clinical care are eligible for inclusion. A total of 40 patients will be included: 30 patients receiving intermittent infusion of piperacillin-tazobactam and 10 patients receiving continuous infusion.
Key inclusion criteria (4 listed)
- Patient is admitted to an ICU.
- Subject is at least 18 years old on the day of the first dosing.
- Is managed with a central venous catheter or arterial line.
- Patient is treated with piperacillin/tazobactam.
Key exclusion criteria (2 listed)
- Has previously participated in this trial.
- Is on renal replacement therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Piperacillin/tazobactamDose according to summary of product characteristics (SPC) or local protocols | Drug | – |
Primary outcome
Total drug clearance
Time frame: 1 day
Pharmacokinetic curves will be taken
2 secondary outcomes
Volume of distribution
Time frame: 1 day
Area under the curve
Time frame: 1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2019.
- Derived from this study: PubMed 35377133Wallenburg E, Ter Heine R, Schouten JA, Raaijmakers J, Ten Oever J, Kolwijck E, Burger DM, Pickkers P, Frenzel T, Bruggemann RJM. An Integral Pharmacokinetic Analysis of Piperacillin and Tazobactam in Plasma and Urine in Critically Ill Patients. Clin Pharmacokinet. 2022 Jun;61(6):907-918. doi: 10.1007/s40262-022-01113-6. Epub 2022 Apr 4.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Bacterial Infections, run by Radboud University Medical Center at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total drug clearance (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03738683, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2019.