Population Pharmacokinetic Modeling to Optimize the Dosage of the Piperacillin / Tazobactam Combination in Patients With Sepsis in Intensive Care (OPT-TAZ)

Population pharmacokinetic modeling mathematically describes the pharmacokinetics of a drug and the variables likely to influence it in a "typical" patient population. We propose to model a Bayesian estimator, taking into account the individual factors that influence exposure to the piperacillin / tazobactam combination in a target population of sepsis, to allow for early assessment of serum Piperacillin / Tazobactam concentration profiles. optimization of dosing regimens. Indeed, pharmacokinetic tools of this type are already regularly successfully applied for other classes of antibiotics or immunosuppressants whose therapeutic index is narrow. They reduce the toxic risk and optimize the effectiveness of these treatments.

Study Overview

• Status: Completed
• Conditions: Resuscitation Patients With Sepsis
• Intervention / Treatment: Drug: Intensive Pharmacokinetic Sampling Cohort; Drug: Sparse Pharmacokinetic Sampling Cohort

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • France
    • Rouen, France, France
      • CHU de ROUEN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Study Population

Patient hospitalized in intensive care for sepsis, involving (i) a suspected or proven infection; (ii) a systemic inflammatory response; (iii) dysfunction of at least one organ, according to the international consensus "sepsis-3"

Description

Inclusion Criteria:

• Major patient (age ≥18 years) male or female.
• Patient hospitalized in intensive care for sepsis, involving (i) a suspected or proven infection; (ii) a systemic inflammatory response; (iii) dysfunction of at least one organ, according to the international consensus "sepsis-3".
• Patient with an arterial catheter that can be used for blood sampling by the time the first dose of piperacillin / tazobactam is administered.
• Patient for whom treatment with piperacillin / tazobactam, alone or in combination with another antibiotic, is prescribed according to the following modalities (drug SPC): scheduled antibiotic treatment for at least 48 hours in IV infusion of 4 g of piperacillin and 0.5 g tazobactam over 3 hours, every 6 hours or every 8 hours.
• Patient affiliated to a social security scheme.
• Patient informed and given his non-opposition. If the patient is unable to do so (emergency situations) the non-opposition will be obtained from the patient's representative.

Exclusion Criteria:

• Treatment with piperacillin and / or tazobactam within 7 days prior to evaluation.
• Patient with a history of allergy to penicillins or β-lactams.
• Kidney function of Kdigo score = 3 (3 times baseline plasma creatinine or plasma creatinine ≥ 354μmol / L or extra-renal clearance, or diuresis <0.3ml / kg / h for ≥ 24h or anuria for ≥ 12h) to not include patients at very high risk of extra-renal clearance within 48 hours.
• Hypersensitivity to the active substances, to any other antibacterial agent of the penicillin class or to any of the excipients.
• History of severe allergic reaction to any other β-lactam.
• Patient being treated with extrarenal treatment.
• Patient being treated with extracorporeal circulation (ECMO).
• Hepatic insufficiency patient with Child C. cirrhosis.
• Patient who refused to participate or refused participation by the representative.
• Person deprived of liberty by an administrative or judicial decision.
• Person under tutorship or curatorship.
• Pregnant or nursing woman.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intensive Pharmacokinetic Sampling Cohort	Drug: Intensive Pharmacokinetic Sampling Cohort; For the first 60 patients, blood samples were collected in 2-mL dry tubes at T0, 90 min, 3 h, 4 h, 5 h, 6 h, 12 h, 24 h, 48 h, and 120 h if infusions are administered over 3 hours every 6 hours; or at T0, 90 min, 3 h, 4 h, 6 h, 8 h, 16 h, 24 h, 48 h, and 120 h if infusions are administered over 3 hours every 8 hours, for piperacillin/tazobactam concentration measurement.
Experimental: Sparse Pharmacokinetic Sampling Cohort	Drug: Sparse Pharmacokinetic Sampling Cohort; For the last 30 patients, blood samples of 2 mL collected in dry tubes at T0, T6h (if administered every 6 hours) or T8h (if administered every 8 hours), then T24h, T48h, and T120h after initiation of treatment via 3-hour infusions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The objective is to develop a Bayesian estimator of the area under the blood concentration curves of the piperacillin / tazobactam combination in resuscitation patients with sepsis.	The primary endpoint of this study is the ability of the pharmacokinetic model developed to predict the AUC of the piperacillin / tazobactam combination at 24 hours after initiation of antibiotic therapy.	24hours

Collaborators and Investigators

• Sponsor: University Hospital, Rouen

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2019
• Primary Completion (Actual): September 12, 2023
• Study Completion (Actual): September 12, 2023

Study Registration Dates

• First Submitted: November 16, 2018
• First Submitted That Met QC Criteria: November 16, 2018
• First Posted (Actual): November 20, 2018

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Piperacillin; Tazobactam
• Other Study ID Numbers: 2017/0384/HP; 2017/384/HP (Registry Identifier: CHU Rouen)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No