Perioperative Pharmacokinetic/Pharmacodynamic Target Attainment of Piperacillin During Major Hepatic and Pancreatic Surgery (PROPHTAZ)

PROPHTAZ: Evaluation of Pharmacokinetic/Pharmacodynamic Target Attainment of Piperacillin During Major Hepatic and Pancreatic Surgery, a Prospective Observational Pharmacokinetic Study

Hepatic and pancreatic surgeries are associated with a high risk of surgical site infections, particularly in patients with preoperative biliary drainage, which is frequently associated with bacterial colonization of bile. In this context, perioperative antibiotic prophylaxis is essential, and recent guidelines recommend the use of piperacillin/tazobactam in selected high-risk patients.

However, piperacillin, like other β-lactam antibiotics, exhibits pharmacokinetic variability that may be exacerbated during major surgery due to factors such as fluid shifts, hypoalbuminemia, and changes in volume of distribution. These alterations may result in suboptimal antibiotic exposure during the perioperative period, potentially compromising prophylactic efficacy.

Despite these concerns, standard dosing regimens remain unchanged across different types of major abdominal surgery, including hepatic and pancreatic procedures, which differ significantly in terms of duration, physiological impact, and intraoperative management.

The PROPHTAZ study is a prospective, single-center observational pharmacokinetic study designed to evaluate whether standard perioperative administration of piperacillin/tazobactam achieves predefined pharmacokinetic/pharmacodynamic (PK/PD) targets in patients undergoing hepatic or pancreatic surgery. The primary objective is to determine the proportion of patients achieving adequate PK/PD exposure during surgery. Secondary objectives include describing perioperative plasma concentrations, assessing pharmacokinetic variability, identifying factors associated with target non-attainment, and comparing outcomes between surgical subgroups.

This study aims to provide clinically relevant data to assess the adequacy of current prophylactic dosing strategies and to support potential optimization of antibiotic administration in high-risk surgical patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Antibiotic Prophylaxis; Hepatic Surgery; Pancreatic Surgey

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Emmanuel NOVY, MD, PhD; Phone Number: +33 383157437; Email: e.novy@chru-nancy.fr

Study Locations

• France
  • Lorraine
    • Vandœuvre-lès-Nancy, Lorraine, France, 54500
      • CHRU de NANCY
      • Contact: Viviane MARTIN, PhD; Phone Number: +33 3155285; Email: v.martin3@chru-nancy.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adult patients undergoing elective hepatic or pancreatic surgery at a tertiary care university hospital (CHRU Nancy, France). Eligible patients are those receiving perioperative antibiotic prophylaxis with piperacillin/tazobactam according to current clinical guidelines, particularly in the context of preoperative biliary drainage or high risk of biliary contamination.

These patients represent a high-risk surgical population for surgical site infections, characterized by complex procedures, potential intraoperative hemodynamic variations, and significant pharmacokinetic variability. Patients are managed in a perioperative setting including the operating room and postoperative admission to a surgical intensive care or intermediate care unit.

Description

Inclusion Criteria:

• Adults > or = to 18 years old
• Scheduled for major hepatic or pancreatic surgery
• Receiving piperacillin/tazobactam as perioperative antibiotic prophylaxis according to guidelines

Exclusion Criteria:

• decline to participate
• Known allergy of beta-lactam

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Adult patients with scheduled pancreatic or major hepatic surgery; Adult patients with scheduled pancreatic surgery or major hepatic receiving piperacillin/tazobactam as antibiotic prophylaxis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK/PD target attainment of piperacillin	Proportion of patients achieving the predefined* PK/PD target during the perioperative period *estimated free concentration of piperacillin (80% of the total concentration) above the MIC of the isolated pathogen from bile samples throughout the surgical procedure (from incision to wound closure)	4 hours after the administration of piperacillin

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma piperacillin concentration	Total (measured) et free (estimated) concentration of piperacilline throughout at two timepoints: surgical incision and wound closure	4 hours after the administration of piperacillin
Factors associated with target attainment	Analysis of clinical and biological covariates associated with pharmacokinetic variability and the achievement of pharmacodynamic targets	4 hours after the administration of piperacillin

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: April 9, 2026
• First Submitted That Met QC Criteria: April 27, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: surgical site infection; piperacillin; PK/PD target atttainment
• Additional Relevant MeSH Terms: Postoperative Complications; Pathologic Processes; Infections; Wound Infection; Pathological Conditions, Signs and Symptoms; Surgical Wound Infection
• Other Study ID Numbers: 2025PI208

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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