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

Sponsor

OHSU Knight Cancer Institute (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04965311

Collaborator

Oregon Health and Science University (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.9

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Pancreatic Carcinoma	Biological: Botulinum Toxin Type A	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

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:

Evaluate the safety of pre-operative BTX injection into the Sphincter of Oddi.
Evaluate the efficacy of pre-operative BTX injection compared to no therapy for the prevention of all POPF.

EXPLORATORY OBJECTIVES:

Using a historical population matched for potential confounding clinicopathologic variables, evaluate differences in POPF.
Using a historical population matched for potential confounding clinicopathologic variables, evaluate differences in clinically relevant POPF (crPOPF).
Using a historical population matched for potential confounding clinicopathologic variables, evaluate differences in postoperative length of hospital stay.
Using a historical population matched for potential confounding clinicopathologic variables, evaluate differences in rate of Clavien-Dindo grade III or greater complications.
Using a historical population matched for potential confounding clinicopathologic variables, evaluate differences in rate of percutaneous drainage.
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 Design

Study Type:

Interventional

Anticipated Enrollment :

63 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

May 1, 2025

Anticipated Study Completion Date :

May 1, 2025

Arms and Interventions

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: AbobotulinumtoxinA Botox Botox Cosmetic Botulinum A Toxin Botulinum Neurotoxin Type A Botulinum Toxin A BTX-A DaxibotulinumtoxinA Dysport EvabotulinumtoxinA IncobotulinumtoxinA OnabotulinumtoxinA Onaclostox Prabotulinumtoxin A Xeomin

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:

AbobotulinumtoxinA

Botox

Botox Cosmetic

Botulinum A Toxin

Botulinum Neurotoxin Type A

Botulinum Toxin A

BTX-A

DaxibotulinumtoxinA

Dysport

EvabotulinumtoxinA

IncobotulinumtoxinA

OnabotulinumtoxinA

Onaclostox

Prabotulinumtoxin A

Xeomin

Outcome Measures

Primary Outcome Measures

Rate of clinically relevant postoperative pancreatic fistula (POPF) [Up to postoperative day 30]
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.

Secondary Outcome Measures

Rate of serious adverse event [Up to 30 days following surgery or study intervention or until date of surgery]
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.
Rate of any POPF [Up to postoperative day 30]
Will be measured and reported with 95% exact confidence interval.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)