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

NCT05753735 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: CASE2223
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Fistula

Keywords

Postoperative pancreatic fistula; Pancreatoduodenectomy

Outcome Measures

Primary Outcomes (1)

• 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.

  56 days

Secondary Outcomes (16)

• Mortality

  At 30 days

• Mortality

  At 90 days

• Index Postoperative Length of Stay

  At 90 days

• Composite Length of Stay

  At 90 days

• Readmission

  At 30 days

Study Arms (2)

Standard perioperative antibiotics

ACTIVE COMPARATOR

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

Extended antibiotic prophylaxis

EXPERIMENTAL

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

Drug: Piperacillin/Tazobactam; Drug: Amoxicillin/ Clavulanic acid

Interventions

Piperacillin/Tazobactam DRUG

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

Extended antibiotic prophylaxis; Standard perioperative antibiotics

Amoxicillin/ Clavulanic acid DRUG

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

Extended antibiotic prophylaxis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Related Publications (2)

• Loftus A, Wu VS, Elshami M, Hue JJ, Ocuin LM. Hospital charge and resource use analysis of extended-spectrum penicillin antibiotic therapy after pancreatoduodenectomy in intermediate- and high-risk patients. HPB (Oxford). 2025 Jan;27(1):63-70. doi: 10.1016/j.hpb.2024.09.011. Epub 2024 Sep 28.

  PMID: 39424467 DERIVED

• Ocuin LM, Loftus A, Elshami M, Hue JJ, Musonza T, Ammori JB, Winter JM, Hardacre JM. Extended antibiotic therapy is associated with a lower rate of clinically relevant postoperative pancreatic fistula after pancreatoduodenectomy in intermediate- and high-risk patients: A single-institution analysis. Surgery. 2024 Feb;175(2):477-483. doi: 10.1016/j.surg.2023.09.049. Epub 2023 Nov 7.

  PMID: 37940433 DERIVED

MeSH Terms

Conditions

Pancreatic Fistula

Interventions

Piperacillin, Tazobactam Drug Combination; Amoxicillin-Potassium Clavulanate Combination

Condition Hierarchy (Ancestors)

Digestive System Fistula; Digestive System Diseases; Pancreatic Diseases; Fistula; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tazobactam; Penicillanic Acid; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Piperacillin; Ampicillin; Penicillin G; Sulfur Compounds; Sulfones; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Clavulanic Acid; Clavulanic Acids; Amoxicillin

Limitations and Caveats

The Principal Investigator left University Hospitals Cleveland Medical Center. Therefore, this clinical trial was terminated prematurely.

Results Point of Contact

• Title: Dr. Nikola Anusic, Protocol Study Coordinator
• Organization: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

a.nikolau@icloud.com

216-421-5986

Study Officials

• Lee M. Ocuin, MD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: February 22, 2023
• First Posted: March 3, 2023
• Study Start: January 18, 2024
• Primary Completion: March 14, 2024
• Study Completion: June 2, 2024
• Last Updated: September 24, 2024
• Results First Posted: September 24, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

US (1)