eXtended Antibiotic Prophylaxis for Intermediate- and High-risk Glands After Pancreatoduodenectomy to Reduce CR-POPF

eXtended Antibiotic Prophylaxis for Intermediate- and High-risk Glands After Pancreatoduodenectomy to Reduce Clinically Relevant PostOperative Pancreatic Fistula: A Phase 2 Randomized Control Trial (X-POPF)

The purpose of this clinical trial is to investigate if prolonged antibiotics after pancreatoduodenectomy can prevent the development of a pancreatic fistula and related complications. Participants who are at high risk of pancreatic fistula will be administered an extended course of antibiotics. While inpatient, the patient will receive these antibiotics through the vein, and after discharge, the antibiotics will be taken by mouth.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Fistula
• Intervention / Treatment: Drug: Piperacillin/Tazobactam; Drug: Amoxicillin/ Clavulanic acid

Detailed Description

Pancreatoduodenectomy (PD) is a commonly performed surgical procedure utilized in the treatment of either localized malignancies or benign conditions that involve the pancreatic head, 2nd/3rd portions of the duodenum, ampulla of Vater, and distal biliary system. Historically, there has been little improvement in the rate of postoperative pancreatic fistula (POPF), which occurs in approximately 10-40% of patients, and is influenced by a number of factors, including surgeon experience, pancreatic gland texture, pancreatic duct size, and underlying diagnosis. POPF is the leaking of enterically contaminated and amylase-rich fluid from the pancreatic-jejunal anastomosis created during PD. This leak may lead to serious complications. The concept of antibiotic mitigation prior to development of a CR-POPF in patients at higher risk of developing CR-POPF is an option that will be explored in this study.

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lee M. Ocuin, MD; Phone Number: 1-800-641-2422; Email: CTUReferral@UHhospitals.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Cleveland Medical Center
      • Contact: Lee M Ocuin, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subject undergoing planned, elective pancreatoduodenectomy at University Hospitals Cleveland Medical Center (UH CMC) for any indication.
• Age >18 years. Pancreatoduodenectomy is rarely, if ever performed in the elective setting for the pediatric population at UH CMC. Therefore, this study will not include this small and different population of patients undergoing pancreatoduodenectomy.
• Subjects must have the ability to understand and the willingness to sign a written informed consent document.
• Creatinine Clearance greater than 40 ml/min

Exclusion Criteria:

• Concurrent participation in another clinical trial, where participation in the proposed clinical trial that prohibits participation in this clinical trial, or where subjects would be actively receiving another investigational agent during the 90-day evaluation period of this study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Piperacillin, Tazobactam, Amoxicillin, Clavulanic Acid or other agents used in this study.
• Subjects who are found to have another active infection or presumed infection at time of surgery who will be treated per standard of care with antibiotics regardless of randomization status.
• Subjects who are found to have metastatic disease at time of planned pancreatoduodenectomy, if surgery is otherwise aborted, or if total pancreatectomy is performed due to interoperative considerations
• Any subject who, while not having history of adverse reaction to similar chemical or biologic composition to Piperacillin, Tazobactam, Amoxicillin, Clavulanic Acid or other agents used in this study, develops a suspected drug reaction to the standard perioperative dose of antibiotic, prior to randomization.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard perioperative antibiotics; The control group will be treated according to current standard perioperative antibiotic practice, and perioperative antibiotics will not exceed 24 hours postoperatively.	Drug: Piperacillin/Tazobactam; Piperacillin/Tazobactam 3.375 g IV every 6 hours while inpatient following surgery, not to exceed 10 days
Experimental: Extended antibiotic prophylaxis; The intervention group will receive an extended duration of current standard perioperative antibiotics, then converted to amoxicillin/clavulanic at discharge	Drug: Piperacillin/Tazobactam; Piperacillin/Tazobactam 3.375 g IV every 6 hours while inpatient following surgery, not to exceed 10 days; Drug: Amoxicillin/ Clavulanic acid; Amoxicillin/ Clavulanic acid 875/125 mg every 12 hours after discharge to complete 10 days total antibiotics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinically relevant (Grade B/C) postoperative pancreatic fistula rate	To demonstrate that extended antibiotic prophylaxis in patients with intermediate/high fistula risk score who undergo PD reduces the rate of clinically relevant postoperative pancreatic fistula in the intervention group.	At 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Rate of mortality	At 30 days
Mortality	Rate of mortality	At 90 days
Index Postoperative Length of Stay	Index postoperative length of stay	At 90 days
Composite Length of Stay	Composite 90-day length of stay	At 90 days
Readmission	Rate of readmission	At 30 days
Readmission	Rate of readmission	At 90 days
Delayed gastric emptying	Rate of delayed gastric emptying	At 90 days
Image-guided drain placement	Rate of image-guided drain placement	At 90 days
Postpancreatectomy hemorrhage	Presence of postpancreatectomy hemorrhage	At 90 days
Superficial surgical site infection	Presence of superficial surgical site infection	At 90 days
Deep surgical site infections	Presence of deep surgical site infections	At 90 days
Deep space infections/intra-abdominal abscess	Presence of deep space infections/intra-abdominal abscess	At 90 days
Additional drain placement	Rate of additional drain placement	At 90 days
Unplanned return to operating room	Measuring occurrences of unplanned return to operating room	At 90 days
Acute kidney injury	Rate of the presence of acute kidney injury	At 90 days
C. difficile colitis	Rate of the presence of C. difficile colitis	At 90 days

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Lee M. Ocuin, MD, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2023
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: February 22, 2023
• First Submitted That Met QC Criteria: February 22, 2023
• First Posted (Actual): March 3, 2023

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Pancreatoduodenectomy; Postoperative pancreatic fistula
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathological Conditions, Anatomical; Pancreatic Diseases; Digestive System Fistula; Fistula; Pancreatic Fistula; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Amoxicillin; Clavulanic Acid; Clavulanic Acids; Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination
• Other Study ID Numbers: CASE2223

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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