SepsisEPICNCT07167524
Evaluation of the Dialytic Clearance of the Combination of Peracillin and Tazobactam
An observational study of Sepsis and Severe Bacterial Infections, run by University Hospital, Rouen at 1 site in France.
Trial summary
Severe bacterial infections, often responsible for sepsis and septic shock, are a major challenge in critical care: approximately 50% of patients are affected, with a mortality rate of up to 40%. Their initial management consists of antibiotic therapy with an adapted spectrum of activity and dose. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Severe Bacterial Infections
- What is being tested?
- Dosage concentration of piperacillin and tazobactam
- How many people
- 24 participants
- Where
- 1 siteFrance
- Study dates
- 1 Oct 2025to 1 Apr 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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: Patients undergoing continuous extra-renal purification (CER) in the various intensive care units of the Rouen University Hospital (surgical, medical, cardiac surgical), receiving concomitant antibiotic therapy with piperacillin-tazobactam (initiated before or after CER) for sepsis or septic shock.
Who may be able to join
- Adult patient over 18 years of age;
- Patient admitted to intensive care with a prescription for cREV (CVVH (pre- or post-dilution (convection)), CVVHD (diffusion), CVVHDF);
- Diagnosed or suspected infection sensitive to the piperacillin-tazobactam combination administered by continuous infusion as part of the patient's standard care;
- Concomitant prescription of piperacillin-tazobactam and cREV;
- Patient affiliated with a social security scheme;
- Adult who has read and understood the information letter and has not expressed non-opposition. Due to the potential life-threatening emergency, if the patient is unable to express their non-opposition, the consent of a trusted person or, where applicable, relatives will be sought.
Who cannot join
- Documented or suspected allergy to penicillins;
- Opposition from the patient or trusted person;
- Pregnant, childbirth, or breastfeeding woman;
- Minor patient;
- Person deprived of liberty by an administrative or judicial decision;
- Person placed under judicial protection, guardianship, or curatorship.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site
University Rouen Hospital
Rouen, 76031
Domitille DR RENARD, Doctor, 02 32 88 33 27 ext. +33, Domitille.Renard@chu-rouen.fr
About this study
Official title: Evaluation of the Dialytic Clearance of the Combination of Peracillin and Tazobactam in Patients Receiving Continuous Renal Replacement Therapy in Intensive Care
Severe bacterial infections, often responsible for sepsis and septic shock, are a major challenge in critical care: approximately 50% of patients are affected, with a mortality rate of up to 40%. Their initial management consists of antibiotic therapy with an adapted spectrum of activity and dose. One of the most widely used antibiotic therapies in intensive care is the piperacillin-tazobactam (pip-taz) combination, a beta-lactam combined with a beta-lactamase inhibitor, which is indicated probabilistically in many infections (pneumopathies, intra-abdominal infections, urinary tract infections, etc.). Mortality rates of up to 40%. Their initial management consists of antibiotic therapy with an appropriate spectrum of activity and dose. One of the most widely used antibiotic therapies in intensive care is the piperacillin-tazobactam (pip-taz) combination, a beta-lactam combined with a beta-lactamase inhibitor, which is indicated probabilistically in many infections (pneumonia, intra-abdominal infections, urinary tract infections, etc.).
Intensive care patients with septic shock exhibit specific pharmacokinetics with an increased volume of distribution, notably due to significant capillary leakage, often disrupted hepatic metabolism, possible hypoalbuminemia, the presence of renal hyperclearance in the initial phase or conversely, the onset of renal failure with altered glomerular filtration rate, sometimes leading to extrarenal clearance, changes that have consequences for the efficacy and toxicity of the administered antibiotic therapy. Sepsis itself also causes renal dysfunction, with the main pathophysiological hypotheses being an alteration of microcirculation, cellular metabolic reprogramming, and deregulation of the inflammatory response. It is therefore essential to focus on the dosages administered and the pharmacokinetics of these patients. Indeed, underdosing is associated with the emergence of resistance and a poorer prognosis in intensive care patients: increased risk of treatment failure, length of stay and mortality. Conversely, significant overdoses can be associated with a poorer renal prognosis, seizures, encephalopathy which can lead to delayed awakening, prolonged duration of mechanical ventilation and intensive care stay.
Read the detailed description
Pip-taz is administered intravenously due to non-absorption via the oral route. It is weakly bound to plasma proteins (21%), inducing good clearance of extrarenal clearance (fraction extracted in 4 hours: 23.6% of the administered dose). Its plasma half-life is 60 minutes. This molecule is not metabolized, and is therefore independent of liver function. It is eliminated mainly in active form in the urine (65%) and bile (35%). Thus, the main determinant of pip-taz clearance is renal clearance, or continuous extrarenal clearance (CER) in dialysis patients in intensive care.
Pip-taz is characterized by time-dependent pharmacodynamics, with better coverage with continuous infusions compared to discontinuous infusions. However, there is no well-defined pattern in patients undergoing continuous extra-renal purification. Despite recommendations regarding antibiotic dosages for use in intensive care, the lack of data regarding patients undergoing continuous renal replacement therapy (CRRE) remains a major and complex problem in optimizing treatment, as these patients present with unique pharmacokinetics, with an increased risk of treatment failure and mortality. Furthermore, there has been a change in practices in recent years, with pip-taz being administered by continuous infusion and increasingly less by discontinuous infusion, in accordance with the latest recommendations.
To our knowledge, few studies have examined the pharmacokinetics of the pip-taz combination in patients undergoing cCRRE in intensive care. Most of these rare studies did not use standard pip-taz dosages, did not examine the clinical and biological variables influencing pip-taz clearance, and none have examined the impact of any preserved diuresis. Furthermore, there are no data on the kinetics of tazobactam in this population. It therefore seems relevant, given the frequent use of this antibiotic therapy in patients undergoing cERE, to accurately assess the clearance of piperacillin and tazobactam in this population. From a precision medicine perspective, these data could contribute to the construction of a pharmacokinetic model using a population approach, based on blood, urine, and effluent samples, in order to provide a tool to assist in the prescription of this antibiotic therapy in intensive care to reduce iatrogenicity and optimize its effectiveness.
- Conditions
- Sepsis, Severe Bacterial Infections
- Being tested
- Dosage concentration of piperacillin and tazobactam
- Keywords
- medical resuscitation, antibiotic therapy, clearance of piperacillin and tazobactam
- Medical subject headings
- Sepsis, Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dosage concentration of piperacillin and tazobactamBiological
The concentration of piperacillin and tazobactam will be quantified by liquid chromatography coupled with tandem mass spectrometry (HPLC-MS² - CIC-CRB 1404) at each of these times by transposition of the method already used in current practice.
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of continuous extrarenal clearance (CERC) of piperacillin in patients with infection in intensive care
The cERC clearance of piperacillin will depend on the type of cERC used, thus determining a clearance:
- diffusion (dialysis, continuous venomous hemodialysis (CVVHD)),
- convection (filtration, continuous venomous hemofiltration (CVVH)),
- diffusion and convection (dialysis and filtration, continuous venomous hemodiafiltration (CVVHDF)).
Each of these clearances will be characterized by different formulas, based on the collection of the following parameters: pre- and post-filter concentrations, concentration in the dialysate/filtrate/effluent, cERC flow rate for diffusion and convection, hematocrit, and partition coefficient of the substance between whole blood and plasma.
Measured: At Enrollment visit, Time 15 minutes, 30 minutes and 45 minutes, Time 1 hour, 3 hours, 6 hours, 8 hours, 12 hours, 24 hours and 36 hours in pre-filter (before pre-dilution when present), post-filter (after post-dilution when present)
Secondary outcomes (6)
Determination of EERc clearance of tazobactam
The cERC clearance of tazobactam will depend on the type of cERC used, thus determining a clearance: - diffusion (dialysis, continuous venomous hemodialysis (CVVHD)), - convection (filtration, continuous venomous hemofiltration (CVVH)), - diffusion and convection (dialysis and filtration, continuous venomous hemodiafiltration (CVVHDF)). Each of these clearances will be characterized by different formulas, based on the collection of the following parameters: pre- and post-filter concentrations, concentration in the dialysate/filtrate/effluent, cERC flow rate for diffusion and convection, hematocrit, and partition coefficient of the substance between whole blood and plasma.
Measured: At Enrollment visit, Time 15 minutes, 30 minutes and 45 minutes, Time 1 hour, 3 hours, 6 hours, 8 hours, 12 hours, 24 hours and 36 hours in pre-filter (before pre-dilution when present), post-filter (after post-dilution when present)
Evaluation of total clearance of piperacillin in patients with preserved residual diuresis.
The total clearance (CLT) of piperacillin will be determined by considering that they correspond to the sum of the renal clearance (CLR) and the clearance of the EERc (CLEERc). Thus, CLT = CLR + CLEERc. In the absence of diuresis, CLR=0 will be considered and therefore CLT = CLEERc.
Measured: At Enrollment visit, Time 15 minutes, 30 minutes and 45 minutes, Time 1 hour, 3 hours, 6 hours, 8 hours, 12 hours, 24 hours and 36 hours in pre-filter (before pre-dilution when present), post-filter (after post-dilution when present)
Evaluation of total clearance of tazobactam in patients with preserved residual diuresis.
The total clearance (CLT) of tazobactam will be determined by considering that they correspond to the sum of the renal clearance (CLR) and the clearance of the EERc (CLEERc). Thus, CLT = CLR + CLEERc. In the absence of diuresis, CLR=0 will be considered and therefore CLT = CLEERc.
Measured: At Enrollment visit, Time 15 minutes, 30 minutes and 45 minutes, Time 1 hour, 3 hours, 6 hours, 8 hours, 12 hours, 24 hours and 36 hours in pre-filter (before pre-dilution when present), post-filter (after post-dilution when present)
Description of the evolution of plasma concentrations of piperacillin over time.
Plasma concentrations of piperacillin over time will be evaluated using a population pharmacokinetic model using a nonlinear mixed-effects regression model.
Measured: At 36 hours
Description of the evolution of plasma concentrations of tazobactam over time.
Plasma concentrations of tazobactam over time will be evaluated using a population pharmacokinetic model using a nonlinear mixed-effects regression model.
Measured: At 36 hours
Development of a dosage regimen to optimize the benefit/risk balance
A dosage regimen to optimize the benefit/risk balance in this population will be developed by plotting the probability curves of reaching the therapeutic target (PTA) as a function of increasing MICs. The pharmacodynamic indices of efficacy retained will be the fraction of time where the free piperacillin concentration is greater than 1x the MIC (fT > 1xMIC = 100%) and 4x the MIC (fT > 4xMIC = 100%).
Measured: At 36 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2025
- Study start1 Oct 2025 (estimated)
- Primary completion1 Oct 2027 (estimated)
- Study completion1 Apr 2028 (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 University Hospital, RouenThe 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
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07167524
- Sponsor's protocol ID
- 2023/0306/OB
- Other IDs
- 2025-A00885-44
- Acronym
- EPIC
- Status last verified
- Aug 2025
- First submitted
- 3 Sep 2025
- Last updated
- 11 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The data provided will be the property of the sponsor and will be used solely for its own research activities.
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Dialytic Clearance of the Combination of Peracillin and Tazobactam in Patients Receiving Continuous Renal Replacement Therapy in Intensive Care
- ClinicalTrials.gov ID
- NCT07167524
- Acronym / sponsor ID
- EPIC / 2023/0306/OB
- Conditions
- Sepsis, Severe Bacterial Infections
- Keywords
- medical resuscitation, antibiotic therapy, clearance of piperacillin and tazobactam
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Study start
- 1 Oct 2025 (estimated)
- Primary completion
- 1 Oct 2027 (estimated)
- Study completion
- 1 Apr 2028 (estimated)
- First posted
- 11 Sep 2025 (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.
Severe bacterial infections, often responsible for sepsis and septic shock, are a major challenge in critical care: approximately 50% of patients are affected, with a mortality rate of up to 40%. Their initial management consists of antibiotic therapy with an adapted spectrum of activity and dose. One of the most widely used antibiotic therapies in intensive care is the piperacillin-tazobactam (pip-taz) combination, a beta-lactam combined with a beta-lactamase inhibitor, which is indicated probabilistically in many infections (pneumopathies, intra-abdominal infections, urinary tract infections, etc.). Mortality rates of up to 40%. Their initial management consists of antibiotic therapy with an appropriate spectrum of activity and dose. One of the most widely used antibiotic therapies in intensive care is the piperacillin-tazobactam (pip-taz) combination, a beta-lactam combined with a beta-lactamase inhibitor, which is indicated probabilistically in many infections (pneumonia, intra-abdominal infections, urinary tract infections, etc.).
Intensive care patients with septic shock exhibit specific pharmacokinetics with an increased volume of distribution, notably due to significant capillary leakage, often disrupted hepatic metabolism, possible hypoalbuminemia, the presence of renal hyperclearance in the initial phase or conversely, the onset of renal failure with altered glomerular filtration rate, sometimes leading to extrarenal clearance, changes that have consequences for the efficacy and toxicity of the administered antibiotic therapy. Sepsis itself also causes renal dysfunction, with the main pathophysiological hypotheses being an alteration of microcirculation, cellular metabolic reprogramming, and deregulation of the inflammatory response. It is therefore essential to focus on the dosages administered and the pharmacokinetics of these patients. Indeed, underdosing is associated with the emergence of resistance and a poorer prognosis in intensive care patients: increased risk of treatment failure, length of stay and mortality. Conversely, significant overdoses can be associated with a poorer renal prognosis, seizures, encephalopathy which can lead to delayed awakening, prolonged duration of mechanical ventilation and intensive care stay.
Detailed description
Pip-taz is administered intravenously due to non-absorption via the oral route. It is weakly bound to plasma proteins (21%), inducing good clearance of extrarenal clearance (fraction extracted in 4 hours: 23.6% of the administered dose). Its plasma half-life is 60 minutes. This molecule is not metabolized, and is therefore independent of liver function. It is eliminated mainly in active form in the urine (65%) and bile (35%). Thus, the main determinant of pip-taz clearance is renal clearance, or continuous extrarenal clearance (CER) in dialysis patients in intensive care.
Pip-taz is characterized by time-dependent pharmacodynamics, with better coverage with continuous infusions compared to discontinuous infusions. However, there is no well-defined pattern in patients undergoing continuous extra-renal purification. Despite recommendations regarding antibiotic dosages for use in intensive care, the lack of data regarding patients undergoing continuous renal replacement therapy (CRRE) remains a major and complex problem in optimizing treatment, as these patients present with unique pharmacokinetics, with an increased risk of treatment failure and mortality. Furthermore, there has been a change in practices in recent years, with pip-taz being administered by continuous infusion and increasingly less by discontinuous infusion, in accordance with the latest recommendations.
To our knowledge, few studies have examined the pharmacokinetics of the pip-taz combination in patients undergoing cCRRE in intensive care. Most of these rare studies did not use standard pip-taz dosages, did not examine the clinical and biological variables influencing pip-taz clearance, and none have examined the impact of any preserved diuresis. Furthermore, there are no data on the kinetics of tazobactam in this population. It therefore seems relevant, given the frequent use of this antibiotic therapy in patients undergoing cERE, to accurately assess the clearance of piperacillin and tazobactam in this population. From a precision medicine perspective, these data could contribute to the construction of a pharmacokinetic model using a population approach, based on blood, urine, and effluent samples, in order to provide a tool to assist in the prescription of this antibiotic therapy in intensive care to reduce iatrogenicity and optimize its effectiveness.
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
- Patients undergoing continuous extra-renal purification (CER) in the various intensive care units of the Rouen University Hospital (surgical, medical, cardiac surgical), receiving concomitant antibiotic therapy with piperacillin-tazobactam (initiated before or after CER) for sepsis or septic shock.
Key inclusion criteria (6 listed)
- Adult patient over 18 years of age;
- Patient admitted to intensive care with a prescription for cREV (CVVH (pre- or post-dilution (convection)), CVVHD (diffusion), CVVHDF);
- Diagnosed or suspected infection sensitive to the piperacillin-tazobactam combination administered by continuous infusion as part of the patient's standard care;
- Concomitant prescription of piperacillin-tazobactam and cREV;
- Patient affiliated with a social security scheme;
Key exclusion criteria (6 listed)
- Documented or suspected allergy to penicillins;
- Opposition from the patient or trusted person;
- Pregnant, childbirth, or breastfeeding woman;
- Minor patient;
- Person deprived of liberty by an administrative or judicial decision;
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 |
|---|---|---|
| Dosage concentration of piperacillin and tazobactamThe concentration of piperacillin and tazobactam will be quantified by liquid chromatography coupled with tandem mass spectrometry (HPLC-MS² - CIC-CRB 1404) at each of these times by transposition of the method already used in current practice. | Biological | – |
Primary outcome
Determination of continuous extrarenal clearance (CERC) of piperacillin in patients with infection in intensive care
Time frame: At Enrollment visit, Time 15 minutes, 30 minutes and 45 minutes, Time 1 hour, 3 hours, 6 hours, 8 hours, 12 hours, 24 hours and 36 hours in pre-filter (before pre-dilution when present), post-filter (after post-dilution when present)
The cERC clearance of piperacillin will depend on the type of cERC used, thus determining a clearance: * diffusion (dialysis, continuous venomous hemodialysis (CVVHD)), * convection (filtration, continuous venomous hemofiltration (CVVH)), * diffusion and convection (dialysis and filtration, continuous venomous hemodiafiltration (CVVHDF)). Each of these clearances will be characterized by different formulas, based on the collection of the following parameters: pre- and post-filter concentrations, concentration in the dialysate/filtrate/effluent, cERC flow rate for diffusion and convection, hematocrit, and partition coefficient of the substance between whole blood and plasma.
6 secondary outcomes
Determination of EERc clearance of tazobactam
Time frame: At Enrollment visit, Time 15 minutes, 30 minutes and 45 minutes, Time 1 hour, 3 hours, 6 hours, 8 hours, 12 hours, 24 hours and 36 hours in pre-filter (before pre-dilution when present), post-filter (after post-dilution when present)
Evaluation of total clearance of piperacillin in patients with preserved residual diuresis.
Time frame: At Enrollment visit, Time 15 minutes, 30 minutes and 45 minutes, Time 1 hour, 3 hours, 6 hours, 8 hours, 12 hours, 24 hours and 36 hours in pre-filter (before pre-dilution when present), post-filter (after post-dilution when present)
Evaluation of total clearance of tazobactam in patients with preserved residual diuresis.
Time frame: At Enrollment visit, Time 15 minutes, 30 minutes and 45 minutes, Time 1 hour, 3 hours, 6 hours, 8 hours, 12 hours, 24 hours and 36 hours in pre-filter (before pre-dilution when present), post-filter (after post-dilution when present)
Description of the evolution of plasma concentrations of piperacillin over time.
Time frame: At 36 hours
Description of the evolution of plasma concentrations of tazobactam over time.
Time frame: At 36 hours
Development of a dosage regimen to optimize the benefit/risk balance
Time frame: At 36 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2025.
- Individual participant dataSharing planned: No. The data provided will be the property of the sponsor and will be used solely for its own research activities.
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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.
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 Severe Bacterial Infections, run by University Hospital, Rouen at 1 site in France.
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 6 inclusion and 6 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: opening soon, as of the sponsor's last update on 11 Sep 2025. 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 France. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Camille CR RENARD, Doctor (02 32 88 33 27 ext. +33, Domitille.Renard@chu-rouen.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determination of continuous extrarenal clearance (CERC) of piperacillin in patients with infection in intensive care (time frame: At Enrollment visit, Time 15 minutes, 30 minutes and 45 minutes, Time 1 hour, 3 hours, 6 hours, 8 hours, 12 hours, 24 hours and 36 hours in pre-filter (before pre-dilution when present), post-filter (after post-dilution when present)). 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 11 Sep 2025.