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

Pancreatic Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04965311
• Other study ID #: STUDY00022619
• Secondary ID: NCI-2021-06239ST
• Status: Recruiting
• Phase: Phase 2
• Start date: March 1, 2023
• Est. completion date: May 1, 2025

Study information

• Verified date: February 2024
• Source: OHSU Knight Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 63
• Est. completion date: May 1, 2025
• Est. primary completion date: May 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Fistula
• Pancreatic Carcinoma
• Pancreatic Fistula
• Pancreatic Neoplasms

Intervention

Biological:
• Botulinum Toxin Type A
Given via endoscopic injection into intraduodenal sphincter of Oddi segment

Locations

Country	Name	City	State
United States	OHSU Knight Cancer Institute	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
OHSU Knight Cancer Institute	Oregon Health and Science University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Rate of any POPF	Will be measured and reported with 95% exact confidence interval.	Up to postoperative day 30