Secretin Infusion to Prevent Pancreatic Leaks Following Pancreatic Resection

NCT ID: NCT02160808

Last Updated: 2020-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 170 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2019-09-21

Brief Summary

Pancreatic leaks complicate pancreatic resection in approximately 20% of cases. The pancreatic anastomosis or repair has been referred to as the Achilles heel of pancreatic surgery. Unfortunately, despite recognition of this problem and multiple operative techniques proposed to prevent this complication, leaks continue to represent a major cause of morbidity for patients undergoing pancreatic surgery. Treatment of leaks often requires nutritional support with total parenteral nutrition to diminish the leak in addition to invasive interventions to contain the leak with drains, stents or in severe cases, reoperation. Experiential data suggest that intra-operative infusions of secretin, a naturally occurring hormone that stimulates bicarbonate release from the pancreas, following resection but just prior to abdomen closure, may identify a leak if present. If secretin can demonstrate evidence of leaking intra-operatively, the pancreatic duct leak may be able to be fixed prior to abdominal closure. The investigators aim to determine if giving an intra-operative infusion of secretin will allow for identification and treatment of leaks after pancreatic reconstruction and prior to abdominal closure, leading to a reduction in the rate of pancreatic anastomotic leaks requiring intervention. The investigators will perform a double-blind, randomized pilot study of 176 patients undergoing pancreatic resection (pancreaticoduodenectomy and distal pancreatectomy) at Dartmouth-Hitchcock Medical Center. 88 of those patients will receive an intra-operative secretin infusion prior to abdominal closure and 88 will receive a saline placebo. Our primary outcome of interest will be the rate of pancreas duct leaks in each group as measured by the concentration of amylase present in the surgical drains 3 days following surgery.

Detailed Description

We hypothesize that intra-operative, intravenous secretin administration will decrease the rate of pancreatic leaks in patients undergoing pancreatic resection. Our primary objective is to determine if intravenous secretin administration will decrease the amount of pancreatic leaks as measured by the 2016 ISGPS definition of pancreatic leaks. Our 1) secondary objectives are to determine if intra-operative intravenous secretin administration changes the management of the pancreatic resection margin intra-operatively and 2) Length of hospital stay.

Use a level of detail similar to what would be used when submitting an article for publication in a peer reviewed journal. Explain the study procedures, data collection, and analysis process. Please define terms and explain concepts which might be confusing to reviewers who are not expert in the area of the study. If a formal protocol for the study exists, page references to the protocol are acceptable.

This study design is a prospective, double-blind, randomized-controlled trial. We will enroll patients in our institution undergoing pancreatic resection to receive either 1) one dose weight-based Secretin to be given once the closure of the pancreatic resection margin is complete 2) saline placebo.

Consent and basic demographics will be garnered by the physician in an office visit once the surgery has been scheduled and consent for the surgery is being obtained. The consent will be validated by the treating surgeon in the pre-procedure area on the day of the surgery.

The patient will undergo the scheduled surgery. Once the pancreatic anastomosis has been deemed acceptable by the attending physician, but prior to abdominal closure, the patient will be randomized to receive either Secretin (0.2 mcg/kg) or saline placebo. The attending surgeon will be blinded to this assignment.

10 minutes after receiving the Secretin or placebo, the attending surgeon will examine the anastomosis or repaired cut edge of the pancreas to determine if leakage of pancreatic fluid is noted, leak location(s), type (side branch/main duct) and whether any further intervention was performed in an effort to close the leak. Specifics of operative intervention will be documented. The patient will then undergo standard surgical closure of the abdomen.

As is standard of care at DHMC, surgical drains will be placed adjacent to the anastomosis and drain amylase output will be checked on POD #1, POD#3 and POD#5. Pancreatic leak is defined according to the International Study Group of Pancreatic Fistula (ISGPF) definition as amylase drainage of greater than a 3-fold elevation above the upper limit of normal in serum through the surgically placed drains on POD #3. Randomization assignments will be revealed once the patient has been discharged from the hospital following their initial surgical intervention. A follow-up visit with the patient two weeks following discharge, will evaluate for any evidence of ongoing pancreatic duct leak.

The primary outcome of interest will be the presence of pancreatic leaks based on the drain amylase on POD#3. Secondary outcomes will include the technical interventions intra-operatively directed to leak closure or manipulation of the anastomosis following Secretin or placebo stimulation and the length of hospitalization.

Patient demographics, risk factors, operative technique, randomization assignment and outcome data will be recorded on standard case report forms - See Case Report Forms in Appendix. Data will be stored in an encrypted hard-drive by a single agent (Gardner) who is the only researcher who has access to the randomization data.

Conditions

Injury of Body of Pancreas

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Secretin

Stimulate pancreatic secretion

Group Type: ACTIVE_COMPARATOR

Secretin

Intervention Type: DRUG

Drug to stimulate pancreatic secretion

Saline

Placebo should not stimulate the pancreas to release its fluids

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Secretin

Drug to stimulate pancreatic secretion

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Scheduled for pancreatic surgery requiring pancreatic resection at DHMC

2. Age greater than 18 years old

3. Ability to provide written informed consent

Exclusion Criteria

1. Inability to provide written informed consent

2. Current ongoing acute pancreatitis

3. Pregnant or nursing mothers

4. Any medical condition which in the judgment of the Investigator renders participation in this study medically inadvisable.

5. Participation in an investigational clinical study for a drug or medical device within 30 days prior to Visit 1.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Timothy Gardner

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Countries

United States

References

Smith KD, Barth RJ, Colacchio TA, Chevalier JI, Bergmann LE, Purich ED, Gardner TB. Effect of intraoperative secretin on operative outcomes in pancreatic resection: A randomized controlled trial. Pancreatology. 2021 Apr;21(3):515-521. doi: 10.1016/j.pan.2021.02.002. Epub 2021 Feb 8.

Reference Type: DERIVED

PMID: 33602643 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

D13208 TBG-01

Identifier Type: -

Identifier Source: org_study_id