Pancreatic FistulaPhase 2NCT05753735
eXtended Antibiotic Prophylaxis for Intermediate- and High-risk Glands After Pancreatoduodenectomy to Reduce CR-POPF
A Phase 2 study testing Piperacillin/Tazobactam and Amoxicillin/ Clavulanic acid in people with Pancreatic Fistula, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Fistula
- What is being tested?
- Piperacillin/Tazobactam and Amoxicillin/ Clavulanic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jan 2024to 2 Jun 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
About this study
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)
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.
Read the 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.
- Conditions
- Pancreatic Fistula
- Being tested
- Piperacillin/Tazobactam, Amoxicillin/ Clavulanic acid
- Keywords
- Postoperative pancreatic fistula, Pancreatoduodenectomy
- Medical subject headings
- Pancreatic Fistula
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Piperacillin/TazobactamDrug
Piperacillin/Tazobactam 3.375 g IV every 6 hours while inpatient following surgery, not to exceed 10 days
Amoxicillin/ Clavulanic acidDrug
Amoxicillin/ Clavulanic acid 875/125 mg every 12 hours after discharge to complete 10 days total antibiotics
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Drug: Piperacillin/Tazobactam; Drug: Amoxicillin/ Clavulanic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 56 days
Secondary outcomes (16)
Mortality
Rate of mortality
Measured: At 30 days
Mortality
Rate of mortality
Measured: At 90 days
Index Postoperative Length of Stay
Index postoperative length of stay
Measured: At 90 days
Composite Length of Stay
Composite 90-day length of stay
Measured: At 90 days
Readmission
Rate of readmission
Measured: At 30 days
Readmission
Rate of readmission
Measured: At 90 days
Delayed Gastric Emptying
Rate of delayed gastric emptying
Measured: At 90 days
Image-guided Drain Placement
Rate of image-guided drain placement
Measured: At 90 days
Postpancreatectomy Hemorrhage
Presence of postpancreatectomy hemorrhage
Measured: At 90 days
Superficial Surgical Site Infection
Presence of superficial surgical site infection
Measured: At 90 days
Deep Surgical Site Infections
Presence of deep surgical site infections
Measured: At 90 days
Deep Space Infections/Intra-abdominal Abscess
Presence of deep space infections/intra-abdominal abscess
Measured: At 90 days
Additional Drain Placement
Rate of additional drain placement
Measured: At 90 days
Unplanned Return to Operating Room
Measuring occurrences of unplanned return to operating room
Measured: At 90 days
Acute Kidney Injury
Rate of the presence of acute kidney injury
Measured: At 90 days
C. Difficile Colitis
Rate of the presence of C. difficile colitis
Measured: At 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2023
- Study start18 Jan 2024
- Primary completion14 Mar 2024
- Study completion2 Jun 2024
Why it stopped: Principal investigator left the institution.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pancreatic FistulaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lee M. Ocuin, MD, Principal investigator, University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05753735
- Sponsor's protocol ID
- CASE2223
- Status last verified
- Sep 2024
- First submitted
- 22 Feb 2023
- Last updated
- 24 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 39424467Ocuin 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.
PubMed 37940433
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05753735
- Acronym / sponsor ID
- CASE2223
- Conditions
- Pancreatic Fistula
- Keywords
- Postoperative pancreatic fistula, Pancreatoduodenectomy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Principal investigator left the institution.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 18 Jan 2024 (actual)
- Primary completion
- 14 Mar 2024 (actual)
- Study completion
- 2 Jun 2024 (actual)
- First posted
- 3 Mar 2023 (actual)
- Results
- Posted 24 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This study will be a randomized, controlled, unblinded, double-arm study with 2:1 randomization to the intervention group.
| Arm | Type | Receives |
|---|---|---|
| Standard perioperative antibiotics | Active comparator | Drug: Piperacillin/TazobactamThe control group will be treated according to current standard perioperative antibiotic practice, and perioperative antibiotics will not exceed 24 hours postoperatively. |
| Extended antibiotic prophylaxis | Experimental | Drug: Piperacillin/Tazobactam, Drug: Amoxicillin/ Clavulanic acidThe intervention group will receive an extended duration of current standard perioperative antibiotics, then converted to amoxicillin/clavulanic at discharge |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Piperacillin/TazobactamPiperacillin/Tazobactam 3.375 g IV every 6 hours while inpatient following surgery, not to exceed 10 days | Drug | Extended antibiotic prophylaxis, Standard perioperative antibiotics |
| Amoxicillin/ Clavulanic acidAmoxicillin/ Clavulanic acid 875/125 mg every 12 hours after discharge to complete 10 days total antibiotics | Drug | Extended antibiotic prophylaxis |
Primary outcome
Clinically Relevant (Grade B/C) Postoperative Pancreatic Fistula Rate
Time frame: 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.
16 secondary outcomes
Mortality
Time frame: At 30 days
Mortality
Time frame: At 90 days
Index Postoperative Length of Stay
Time frame: At 90 days
Composite Length of Stay
Time frame: At 90 days
Readmission
Time frame: At 30 days
Readmission
Time frame: At 90 days
Delayed Gastric Emptying
Time frame: At 90 days
Image-guided Drain Placement
Time frame: At 90 days
Postpancreatectomy Hemorrhage
Time frame: At 90 days
Superficial Surgical Site Infection
Time frame: At 90 days
Deep Surgical Site Infections
Time frame: At 90 days
Deep Space Infections/Intra-abdominal Abscess
Time frame: At 90 days
Additional Drain Placement
Time frame: At 90 days
Unplanned Return to Operating Room
Time frame: At 90 days
Acute Kidney Injury
Time frame: At 90 days
C. Difficile Colitis
Time frame: At 90 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39424467Loftus 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.
- Derived from this study: PubMed 37940433Ocuin 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lee M. Ocuin, MD principal investigator
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Piperacillin/Tazobactam and Amoxicillin/ Clavulanic acid in people with Pancreatic Fistula, run by Case Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinically Relevant (Grade B/C) Postoperative Pancreatic Fistula Rate (time frame: 56 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05753735, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2024.