Evaluation of Postoperative Piperacillin/Tazobactam Therapy Versus Prophylaxis for Surgical Site Infection in Pancreaticoduodenectomy Patients with Preoperative Biliary Stent

The primary objective of this study is to compare two broad-spectrum antibiotic treatment modalities, specifically **Piperacillin/Tazobactam**, to demonstrate the superiority of a 5-day post-operative antibiotic therapy over antibiotic prophylaxis in reducing the occurrence of surgical site infections (SSI) in patients undergoing pancreaticoduodenectomy with a preoperative biliary stent. This is clinically relevant as it aims to optimize post-operative care and potentially reduce infection rates, which can significantly impact patient recovery and healthcare costs.

Secondary objectives include:

• Evaluation of the overall morbidity associated with different treatment modes by recording surgical complications.
• Evaluation of antibiotic resistance profiles and their impact on post-operative complications.
• Assessment of the pathogenicity of bacteriological and fungal co-contamination.
• Evaluation of the impact of complications after bile drainage and neoadjuvant treatment on the bacteriological and fungal profile of biliculture.
• Cost-effectiveness analysis.

The clinical trial involves participants who are **patients with preoperative biliary stent** treated by pancreaticoduodenectomy. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a planned pancreaticoduodenectomy for periampullary neoplasms and must have undergone endoscopic or radiological pre-operative biliary drainage. The trial population was selected based on their ability to comply with the study protocol, as judged by the investigator, and their affiliation with a social security or national health insurance category. Women of childbearing potential are required to use highly effective contraception and have a negative blood pregnancy test at inclusion. The trial also includes postmenopausal women and those who are permanently sterile. The sponsor has not provided information regarding the total number of participants. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, indicating that special considerations are in place to ensure the safety and ethical treatment of participants.

The clinical trial is designed to evaluate the efficacy of two broad-spectrum **antibiotic** treatment modalities, specifically Piperacillin/Tazobactam, in patients undergoing pancreaticoduodenectomy with a preoperative biliary stent. This is a randomized, double-blind, controlled trial aimed at demonstrating the superiority of a 5-day postoperative antibiotic therapy over antibiotic prophylaxis in reducing the occurrence of surgical site infections (SSI). The trial is expected to commence on October 1, 2024, and conclude by December 31, 2026, with the primary endpoint being the presence of organ/space SSI, including postoperative pancreatic fistula and bile leakage, as determined by the Centers for Disease Control and Prevention’s national nosocomial infections surveillance system.

Participants will be involved in the study for a maximum of 6 weeks, with the trial including several key visits. The initial inclusion visit will serve as a screening to ensure participants meet the principal inclusion criteria, such as planned pancreaticoduodenectomy for periampullary neoplasms, preoperative biliary drainage, and age of 18 years or older. Follow-up visits will be scheduled to monitor the occurrence of infectious complications and overall postsurgical morbidity, graded according to the Dindo/Clavien classification, up to postoperative day 90. The end-of-study visit will assess the primary and secondary endpoints, including the correlation between postoperative bacteriological samples and intraoperative bile samples, bacteriological resistance profiles, and the incidence of fungal contamination.

Participants may be terminated early from the study if they fail to comply with the study protocol, experience adverse events that necessitate withdrawal, or if the investigator deems it in the participant's best interest. The trial will also evaluate the incremental cost per infectious complication avoided, providing a comprehensive analysis of the treatment's efficacy and economic impact. The study is not classified as low intervention and is categorized as a Phase III trial, ensuring rigorous assessment of the treatment's safety and effectiveness in the specified patient population.

The clinical trial involves the administration of **Piperacillin/Tazobactam Kabi 4 g/500 mg**, a broad-spectrum antibiotic combination, in the form of a **solution for infusion**. This experimental medication is composed of active substances including **piperacillin sodium**, **tazobactam sodium**, **piperacillin**, **tazobactam**, and **piperacillin monohydrate**. The pharmaceutical form is a powder intended for reconstitution into a solution for intravenous injection. The maximum daily dose is 12 grams, with a total maximum dose of 72 grams over a treatment period not exceeding six days. The administration is conducted intravenously, ensuring direct delivery into the bloodstream for optimal therapeutic effect. The medication is manufactured by Fresenius Kabi France S.A.S. and is not formulated for pediatric use.

In this study, the experimental treatment is compared against a standard-of-care therapy, which serves as the comparator treatment. The trial aims to evaluate the efficacy of a 5-day post-operative antibiotic therapy regimen in reducing the incidence of surgical site infections (SSI) following pancreaticoduodenectomy in patients with a preoperative biliary stent. The study does not utilize a placebo, as the focus is on comparing two active treatment modalities. Participant compliance with the dosing schedule is monitored through regular assessments to ensure adherence to the prescribed treatment regimen.

Efficacy in this clinical trial will be assessed by evaluating the occurrence of surgical site infections (SSI) as the primary endpoint. The presence of organ/space SSI will be determined according to the Centers for Disease Control and Prevention’s national nosocomial infections surveillance system. This includes postoperative pancreatic fistula (POPF) and bile leakage, with positive culture results.

Secondary endpoints will include the assessment of infectious complications at post-operative day 90, overall postsurgical morbidity graded according to the Dindo/Clavien classification and CCI score at post-operative day 90, and specific morbidity due to pancreatic fistula graded according to the International Study Group of Pancreatic Fistula (ISGPF) criteria. Additional secondary endpoints will involve readmission rates at post-operative day 90, duration of hospitalization, correlation between post-operative bacteriological samples and intraoperative bile samples, bacteriological resistance profiles, incidence of fungal contamination, correlation between bacteriological and fungal contaminations, and incremental cost per infectious complication avoided.