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)

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05753735

Enrollment

Registered

2023-03-03

Start date

2024-01-18

Completion date

2024-06-02

Last updated

2024-09-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pancreatic Fistula

Keywords

Postoperative pancreatic fistula, Pancreatoduodenectomy

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.

Interventions

DRUGPiperacillin/Tazobactam

Piperacillin/Tazobactam 3.375 g IV every 6 hours while inpatient following surgery, not to exceed 10 days

DRUGAmoxicillin/ Clavulanic acid

Amoxicillin/ Clavulanic acid 875/125 mg every 12 hours after discharge to complete 10 days total antibiotics

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

NONE

Intervention model description

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

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

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.

Design outcomes

Primary

Measure	Time frame	Description
Clinically Relevant (Grade B/C) Postoperative Pancreatic Fistula Rate	56 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

Measure	Time frame	Description
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
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
Mortality	At 30 days	Rate of mortality
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
Superficial Surgical Site Infection	At 90 days	Presence of superficial surgical site infection

Countries

United States

Participant flow

Participants by arm

Arm	Count
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. Piperacillin/Tazobactam: Piperacillin/Tazobactam 3.375 g IV every 6 hours while inpatient following surgery, not to exceed 10 days	0
Extended Antibiotic Prophylaxis The intervention group will receive an extended duration of current standard perioperative antibiotics, then converted to amoxicillin/clavulanic at discharge Piperacillin/Tazobactam: Piperacillin/Tazobactam 3.375 g IV every 6 hours while inpatient following surgery, not to exceed 10 days Amoxicillin/ Clavulanic acid: Amoxicillin/ Clavulanic acid 875/125 mg every 12 hours after discharge to complete 10 days total antibiotics	3
Total	3

Baseline characteristics

Characteristic	Extended Antibiotic Prophylaxis	Total
Age, Categorical <=18 years	0 Participants	0 Participants
Age, Categorical >=65 years	3 Participants	3 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants	2 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants
Race (NIH/OMB) White	3 Participants	3 Participants
Region of Enrollment United States	3 participants	3 participants
Sex: Female, Male Female	3 Participants	3 Participants
Sex: Female, Male Male	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 0	0 / 3
other Total, other adverse events	0 / 0	0 / 3
serious Total, serious adverse events	0 / 0	0 / 3

Outcome results

Primary

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.

Time frame: 56 days