SepsisNCT02478073
Piperacillin Pharmacokinetics in ICU Patients
An observational study of Sepsis and Septic Shock, run by Aarhus University Hospital at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Septic Shock
- How many people
- 50 participants
- Where
- 1 siteDenmark
- Study dates
- Jun 2015to May 2016
- 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: Critically ill patients with sepsis or septic shock, treated with piperacillin/tazobactam in the Intensive Care Unit (ICU).
Who may be able to join
- Sepsis or septic shock
- Treatment with piperacillin/tazobactam
Who cannot join
- Age under 18 years
- Renal replacement therapy
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Aarhus Univbersity Hospital, Department of Anesthesia and Intensive Care Medicine
Aarhus N, 8200
Jakob Gjedsted, MD, PhD, +45 78451030, jakob.gjedsted@auh.rm.dk
Kristina Öbrink-Hansen, MD, +45 78452845, krobrink@gmail.com
About this study
Official title: Piperacillin Pharmacokinetics in Intensive Care Unit Patients Following Standard Treatment With Intermittent and Continuous Infusion
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).
Read the detailed 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.
- Conditions
- Sepsis, Septic Shock
- Medical subject headings
- Sepsis, Shock, Septic
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Secondary outcomes (1)
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)
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2015 (estimated)
- Study startJun 2015
- Primary completionMay 2016 (estimated)
- Study completionMay 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Aarhus University HospitalThe 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
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aarhus University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jakob Gjedsted, MD, PhD, Principal investigator, Aarhus University Hospital, Department of Anesthesia and Intensive Care Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02478073
- Sponsor's protocol ID
- AB-ICU
- Status last verified
- Jun 2015
- First submitted
- 15 Jun 2015
- Last updated
- 23 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Piperacillin Pharmacokinetics in Intensive Care Unit Patients Following Standard Treatment With Intermittent and Continuous Infusion
- ClinicalTrials.gov ID
- NCT02478073
- Acronym / sponsor ID
- AB-ICU
- Conditions
- Sepsis, Septic Shock
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Aarhus University HospitalUniversity, hospital or other
- Study start
- Jun 2015
- Primary completion
- May 2016 (estimated)
- Study completion
- May 2016 (estimated)
- First posted
- 23 Jun 2015 (estimated)
- 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.
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).
Detailed 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.
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
- Critically ill patients with sepsis or septic shock, treated with piperacillin/tazobactam in the Intensive Care Unit (ICU).
Key inclusion criteria (2 listed)
- Sepsis or septic shock
- Treatment with piperacillin/tazobactam
Key exclusion criteria (2 listed)
- Age under 18 years
- 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.
Primary outcome
Blood-plasma concentration of Piperacillin
Time frame: 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.
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).
1 secondary outcome
Percentage of time above the minimal inhibitory concentration (T>MIC)
Time frame: 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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2015.
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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.
Jakob Gjedsted, MD, PhD principal investigator
Aarhus University Hospital, Department of Anesthesia and Intensive Care Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis and Septic Shock, run by Aarhus University Hospital at 1 site in Denmark.
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 2 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: status not confirmed, as of the sponsor's last update on 23 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kristina Öbrink-Hansen, MD (+45 78452845, krisoebr@rm.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood-plasma concentration of Piperacillin (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Jun 2015.