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

Primary Purpose

Pancreatic Fistula

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Piperacillin/Tazobactam
Amoxicillin/ Clavulanic acid
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Pancreatic Fistula focused on measuring Postoperative pancreatic fistula, Pancreatoduodenectomy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • University Hospitals Cleveland Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard perioperative antibiotics

Extended antibiotic prophylaxis

Arm Description

The control group will be treated according to current standard perioperative antibiotic practice, and perioperative antibiotics will not exceed 24 hours postoperatively.

The intervention group will receive an extended duration of current standard perioperative antibiotics, then converted to amoxicillin/clavulanic at discharge

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
February 22, 2023
Last Updated
June 26, 2023
Sponsor
Case Comprehensive Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT05753735
Brief Title
eXtended Antibiotic Prophylaxis for Intermediate- and High-risk Glands After Pancreatoduodenectomy to Reduce CR-POPF
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 1, 2023 (Anticipated)
Primary Completion Date
June 1, 2026 (Anticipated)
Study Completion Date
September 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Case Comprehensive Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Fistula
Keywords
Postoperative pancreatic fistula, Pancreatoduodenectomy

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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)
Allocation
Randomized
Enrollment
96 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Standard perioperative antibiotics
Arm Type
Active Comparator
Arm Description
The control group will be treated according to current standard perioperative antibiotic practice, and perioperative antibiotics will not exceed 24 hours postoperatively.
Arm Title
Extended antibiotic prophylaxis
Arm Type
Experimental
Arm Description
The intervention group will receive an extended duration of current standard perioperative antibiotics, then converted to amoxicillin/clavulanic at discharge
Intervention Type
Drug
Intervention Name(s)
Piperacillin/Tazobactam
Intervention Description
Piperacillin/Tazobactam 3.375 g IV every 6 hours while inpatient following surgery, not to exceed 10 days
Intervention Type
Drug
Intervention Name(s)
Amoxicillin/ Clavulanic acid
Intervention Description
Amoxicillin/ Clavulanic acid 875/125 mg every 12 hours after discharge to complete 10 days total antibiotics
Primary Outcome Measure Information:
Title
Clinically relevant (Grade B/C) postoperative pancreatic fistula rate
Description
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.
Time Frame
At 90 days
Secondary Outcome Measure Information:
Title
Mortality
Description
Rate of mortality
Time Frame
At 30 days
Title
Mortality
Description
Rate of mortality
Time Frame
At 90 days
Title
Index Postoperative Length of Stay
Description
Index postoperative length of stay
Time Frame
At 90 days
Title
Composite Length of Stay
Description
Composite 90-day length of stay
Time Frame
At 90 days
Title
Readmission
Description
Rate of readmission
Time Frame
At 30 days
Title
Readmission
Description
Rate of readmission
Time Frame
At 90 days
Title
Delayed gastric emptying
Description
Rate of delayed gastric emptying
Time Frame
At 90 days
Title
Image-guided drain placement
Description
Rate of image-guided drain placement
Time Frame
At 90 days
Title
Postpancreatectomy hemorrhage
Description
Presence of postpancreatectomy hemorrhage
Time Frame
At 90 days
Title
Superficial surgical site infection
Description
Presence of superficial surgical site infection
Time Frame
At 90 days
Title
Deep surgical site infections
Description
Presence of deep surgical site infections
Time Frame
At 90 days
Title
Deep space infections/intra-abdominal abscess
Description
Presence of deep space infections/intra-abdominal abscess
Time Frame
At 90 days
Title
Additional drain placement
Description
Rate of additional drain placement
Time Frame
At 90 days
Title
Unplanned return to operating room
Description
Measuring occurrences of unplanned return to operating room
Time Frame
At 90 days
Title
Acute kidney injury
Description
Rate of the presence of acute kidney injury
Time Frame
At 90 days
Title
C. difficile colitis
Description
Rate of the presence of C. difficile colitis
Time Frame
At 90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lee M. Ocuin, MD
Phone
1-800-641-2422
Email
CTUReferral@UHhospitals.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lee M. Ocuin, MD
Organizational Affiliation
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospitals Cleveland Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lee M Ocuin, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

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

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