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

Sponsor

Case Comprehensive Cancer Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05753735

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Fistula	Drug: Piperacillin/Tazobactam Drug: Amoxicillin/ Clavulanic acid	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

96 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This study will be a randomized, controlled, unblinded, double-arm study with 2:1 randomization to the intervention group.This study will be a randomized, controlled, unblinded, double-arm study with 2:1 randomization to the intervention group.

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

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)

Anticipated Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Jun 1, 2026

Anticipated Study Completion Date :

Sep 1, 2026

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Clinically relevant (Grade B/C) postoperative pancreatic fistula rate [At 90 days]
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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.