Endoscopic Botulinum Toxin Injection in the Prevention of Postoperative Pancreatic Fistula Following Distal Pancreatectomy
Primary Purpose
Pancreatic Carcinoma
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Botulinum Toxin Type A
Sponsored by
About this trial
This is an interventional treatment trial for Pancreatic Carcinoma
Eligibility Criteria
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)
Sites / Locations
- OHSU Knight Cancer InstituteRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment of POPF (botulinum toxin type A)
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Rate of any POPF
Will be measured and reported with 95% exact confidence interval.
Full Information
NCT ID
NCT04965311
First Posted
July 7, 2021
Last Updated
July 20, 2023
Sponsor
OHSU Knight Cancer Institute
Collaborators
Oregon Health and Science University
1. Study Identification
Unique Protocol Identification Number
NCT04965311
Brief Title
Endoscopic Botulinum Toxin Injection in the Prevention of Postoperative Pancreatic Fistula Following Distal Pancreatectomy
Official Title
A Phase II Trial of Pre-Operative Endoscopic Botulinum Toxin Injection in the Prevention of Postoperative Pancreatic Fistula Following Distal Pancreatectomy
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2023 (Actual)
Primary Completion Date
May 1, 2025 (Anticipated)
Study Completion Date
May 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
OHSU Knight Cancer Institute
Collaborators
Oregon Health and Science University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
63 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment of POPF (botulinum toxin type A)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Botulinum Toxin Type A
Other Intervention Name(s)
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
Intervention Description
Given via endoscopic injection into intraduodenal sphincter of Oddi segment
Primary Outcome Measure Information:
Title
Rate of clinically relevant postoperative pancreatic fistula (POPF)
Description
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.
Time Frame
Up to postoperative day 30
Secondary Outcome Measure Information:
Title
Rate of serious adverse event
Description
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.
Time Frame
Up to 30 days following surgery or study intervention or until date of surgery
Title
Rate of any POPF
Description
Will be measured and reported with 95% exact confidence interval.
Time Frame
Up to postoperative day 30
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brett C Sheppard, M.D., FACS
Organizational Affiliation
OHSU Knight Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
OHSU Knight Cancer Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brett C. Sheppard, M.D., FACS
Phone
503-494-1502
Email
sheppard@ohsu.edu
First Name & Middle Initial & Last Name & Degree
Brett C. Sheppard, M.D., FACS
12. IPD Sharing Statement
Learn more about this trial
Endoscopic Botulinum Toxin Injection in the Prevention of Postoperative Pancreatic Fistula Following Distal Pancreatectomy
We'll reach out to this number within 24 hrs