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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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)

Conditions
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Pancreatic Fistula

Intervention / Treatment
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* Drug: Piperacillin/Tazobactam
* Drug: Amoxicillin/ Clavulanic acid


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study will be a randomized, controlled, unblinded, double-arm study with 2:1 randomization to the intervention group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard perioperative antibiotics<br>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<br>* Piperacillin/Tazobactam 3.375 g IV every 6 hours while inpatient following surgery, not to exceed 10 days<br>|
| Experimental: Extended antibiotic prophylaxis<br>The intervention group will receive an extended duration of current standard perioperative antibiotics, then converted to amoxicillin/clavulanic at discharge | Drug: Piperacillin/Tazobactam<br>* Piperacillin/Tazobactam 3.375 g IV every 6 hours while inpatient following surgery, not to exceed 10 days<br>Drug: Amoxicillin/ Clavulanic acid<br>* Amoxicillin/ Clavulanic acid 875/125 mg every 12 hours after discharge to complete 10 days total antibiotics<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postoperative pancreatic fistula, Pancreatoduodenectomy