Endoscopic Botulinum Toxin Injection in the Prevention of Postoperative Pancreatic Fistula Following Distal Pancreatectomy

A Phase II Trial of Pre-Operative Endoscopic Botulinum Toxin Injection in the Prevention of Postoperative Pancreatic Fistula Following Distal Pancreatectomy

This phase II trial studies the effect of botulinum toxin (Botox) in preventing postoperative pancreatic fistula after distal pancreatectomy. Postoperative pancreatic fistula (POPF) is a known risk of distal pancreatic surgery, in which leakage of pancreatic digestive liquids causes internal swelling that can be painful (termed inflammation). A valve-like muscle, called the Sphincter of Oddi, opens and closes, controlling the flow of digestive liquids from the liver (bile) and pancreas (pancreatic juice) to the small intestine (duodenum). After surgery, the Sphincter of Oddi may act to block the flow of normal pancreatic secretions, causing secretions to leak into the abdomen resulting in POPF. Botox is a drug that can cause paralysis of muscles. Giving an injection of Botox into the sphincter of Oddi before distal pancreatic surgery may reduce leakage of digestive fluids and potential POPF.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Carcinoma
• Intervention / Treatment: Biological: Botulinum Toxin Type A

Detailed Description

PRIMARY OBJECTIVE:

I. Evaluate the efficacy of pre-operative botulinum toxin type A (BTX) injection compared to no therapy for the prevention of clinically relevant POPF.

SECONDARY OBJECTIVES:

I. Evaluate the safety of pre-operative BTX injection into the Sphincter of Oddi.

II. Evaluate the efficacy of pre-operative BTX injection compared to no therapy for the prevention of all POPF.

EXPLORATORY OBJECTIVES:

I. Using a historical population matched for potential confounding clinicopathologic variables, evaluate differences in POPF.

II. Using a historical population matched for potential confounding clinicopathologic variables, evaluate differences in clinically relevant POPF (crPOPF).

III. Using a historical population matched for potential confounding clinicopathologic variables, evaluate differences in postoperative length of hospital stay.

IV. Using a historical population matched for potential confounding clinicopathologic variables, evaluate differences in rate of Clavien-Dindo grade III or greater complications.

V. Using a historical population matched for potential confounding clinicopathologic variables, evaluate differences in rate of percutaneous drainage.

VI. Using a historical population matched for potential confounding clinicopathologic variables, evaluate differences in rate of unplanned re-operation.

OUTLINE:

Patients receive botulinum toxin type A via endoscopic injection into intraduodenal sphincter of Oddi segment between 7-14 days prior to planned distal pancreas resection.

Patients are followed for 30 days following distal pancreas resection.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Knight Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant scheduled for elective distal pancreatectomy or radical antegrade modular pancreatosplenectomy (RAMPS), via open or laparoscopic technique
• Participant >= 18 years of age
• Ability to understand nature and individual consequences of clinical trial
• Written informed consent from participant or legally authorized representative
• For participants of childbearing potential, a negative pregnancy test and adequate contraception until 14 days after trial intervention

Exclusion Criteria:

• Known hypersensitivity to any BTX preparation or to any of the components in the formulation
• Infection at the proposed injection site, including cholangitis
• Anatomy incompatible with planned intervention (e.g., Roux-en-Y gastric bypass, distal gastrectomy with Roux-en-Y or Billroth II reconstruction)
• Acute pancreatitis within 2 weeks of planned study intervention
• American Society of Anesthesiologists (ASA) score > III
• Serious cardiovascular disease (e.g., myocardial infarction in the past year, New York Heart Association [NYHA] III/IV congestive heart failure, unstable angina)
• Creatinine clearance < 30 mL/min
• Liver cirrhosis (of any Child-Pugh grade)
• Neuromuscular or any neurological disease with associated increased risk for a participant undergoing BTX injection
• Prior BTX administration
• Inability to obtain informed consent due to comprehension or language barrier
• Inability to comply with study and/or follow-up procedures
• Pregnancy or lactation
• Any condition that could result in undue risk for the participant and/or influence outcome measures (in the opinion of the investigator)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment of POPF (botulinum toxin type A); Patients receive botulinum toxin type A via endoscopic injection into intraduodenal sphincter of Oddi segment between 7-14 days prior to planned distal pancreas resection.	Biological: Botulinum Toxin Type A; Given via endoscopic injection into intraduodenal sphincter of Oddi segment; Other Names: Botox; OnabotulinumtoxinA; BTX-A; Xeomin; Dysport; IncobotulinumtoxinA; AbobotulinumtoxinA; Botox Cosmetic; Botulinum Toxin A; DaxibotulinumtoxinA; Botulinum A Toxin; Botulinum Neurotoxin Type A; EvabotulinumtoxinA; Onaclostox; Prabotulinumtoxin A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinically Relevant Postoperative Pancreatic Fistula (POPF)	Defined by standard biochemical definitions of POPF per the International Study Group of Pancreatic Fistula (ISGPF) criteria.	Up to postoperative day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Serious Adverse Event	Using the safety analysis set, the rate of serious adverse events following endoscopic BTX injection into the sphincter of Oddi as a single agent will be determined for participants undergoing distal pancreas resections. The 95% confidence interval will be reported with the point estimate of serious adverse events (SAE) rate.	Prior to surgery up to 30 days post surgery (up to 3 months)
Number of Participants With Any POPF		Prior to surgery up to 30 days post surgery (up to 3 months)

Collaborators and Investigators

• Sponsor: OHSU Knight Cancer Institute
• Collaborators: Oregon Health and Science University
• Investigators: Principal Investigator: Brett C Sheppard, M.D., FACS, OHSU Knight Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Actual): July 10, 2024
• Study Completion (Actual): July 10, 2024

Study Registration Dates

• First Submitted: July 7, 2021
• First Submitted That Met QC Criteria: July 7, 2021
• First Posted (Actual): July 16, 2021

Study Record Updates

• Last Update Posted (Actual): May 13, 2025
• Last Update Submitted That Met QC Criteria: May 9, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Pathological Conditions, Anatomical; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Digestive System Fistula; Pancreatic Neoplasms; Fistula; Pancreatic Fistula; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Neurotransmitter Agents; Membrane Transport Modulators; Cholinergic Agents; Neuromuscular Agents; Acetylcholine Release Inhibitors; Botulinum Toxins, Type A; abobotulinumtoxinA; Botulinum Toxins; incobotulinumtoxinA
• Other Study ID Numbers: STUDY00022619 (Other Identifier: OHSU Knight Cancer Institute); NCI-2021-06239 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No