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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pancreatic Carcinoma

Intervention / Treatment
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* Biological: Botulinum Toxin Type A


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment of POPF (botulinum toxin type A)<br>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<br>* Given via endoscopic injection into intraduodenal sphincter of Oddi segment<br>* Other names: Xeomin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of clinically relevant postoperative pancreatic fistula (POPF) | Defined by standard biochemical definitions of POPF per the International Study Group of Pancreatic Fistula (ISGPF) criteria. will be measured and reported with 95% exact confidence interval. | 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 incidence 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. | Up to 30 days following surgery or study intervention or until date of surgery | 
| Rate of any POPF | Will be measured and reported with 95% exact confidence interval. | Up to postoperative day 30 |