Secretin Infusion to Prevent Pancreatic Leaks Following Pancreatic Resection

• Sponsor: Dartmouth-Hitchcock Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02160808
• Collaborator: (none)
• Enrollment: 170
• Location: 1
• Arms: 2
• Actual Duration (Months): 64.7
• Patients Per Site Per Month: 2.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Injury of Body of Pancreas	Drug: Secretin; Drug: Placebo	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 170 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Secretin Infusion to Prevent Pancreatic Leaks Following Pancreatic Resection
• Actual Study Start Date: May 1, 2014
• Actual Primary Completion Date: Sep 21, 2019
• Actual Study Completion Date: Sep 21, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Secretin Stimulate pancreatic secretion	Drug: Secretin; Drug to stimulate pancreatic secretion
Placebo Comparator: Saline Placebo should not stimulate the pancreas to release its fluids	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Biochemical Leak/Grade B Fistula/Grade C Fistula [3 days]

   Outcome based on revised ISGPS Guidelines which require a three day drain amylase concentration greater than 3x the normal serum amylase concentration. Biochemical leaks are the mildest for of fistula which have no clinical consequence. Grade B fistula are more severe requiring usually percutaneous drainage placement. Grade C fistula are most severe resulting in significant morbidity and/or death.

Secondary Outcome Measures

1. Number of Participants With Intra-operative Intervention, Subsequent Biochemical Leak or B/C Fistula After Drug Administration [Through completion of intra-operative intervention and subsequent biochemical leak, B/C Fistula up to 30 days post-operatively]

   Following the administration of Secretin or Placebo intraoperatively, the surgeon will have the opportunity to evaluate the anastomosis to determine if there is ongoing leak. If there is ongoing leak, then the surgeon will be able to treat the leak intra-operatively prior to operative closure. In those patients in whom an intervention was performed, they were subsequently evaluated to determine if they developed a biochemical leak or grade B/C fistula.

2. Length of Hospitalization [Duration of study - average 30 days]

   Surrogate marker for operative success

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756

Sponsors and Collaborators

• Dartmouth-Hitchcock Medical Center

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 22, 2019

More Information

Publications

None provided.

• Responsible Party: Timothy Gardner, Associate Professor of Medicine, Dartmouth-Hitchcock Medical Center
• ClinicalTrials.gov Identifier: NCT02160808
• Other Study ID Numbers: D13208 TBG-01
• First Posted: Jun 11, 2014
• Last Update Posted: Mar 31, 2020
• Last Verified: Mar 1, 2020

• Additional relevant MeSH terms: Secretin

Study Results

Participant Flow

Arm/Group Title	Secretin	Saline
Arm/Group Description	Stimulate pancreatic secretion Secretin: Drug to stimulate pancreatic secretion	Placebo should not stimulate the pancreas to release its fluids Placebo
Period Title: Overall Study
STARTED	87	83
COMPLETED	87	83
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Secretin	Saline	Total
Arm/Group Description	Stimulate pancreatic secretion Secretin: Drug to stimulate pancreatic secretion	Placebo should not stimulate the pancreas to release its fluids Placebo	Total of all reporting groups
Overall Participants	87	83	170
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.4 (12.3)	63.5 (12.1)	63.45 (12.15)
Sex: Female, Male (Count of Participants)
Female	43 49.4%	33 39.8%	76 44.7%
Male	44 50.6%	50 60.2%	94 55.3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.6 (5.0)	26.7 (6.3)	26.65 (5.8)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Biochemical Leak/Grade B Fistula/Grade C Fistula
Description	Outcome based on revised ISGPS Guidelines which require a three day drain amylase concentration greater than 3x the normal serum amylase concentration. Biochemical leaks are the mildest for of fistula which have no clinical consequence. Grade B fistula are more severe requiring usually percutaneous drainage placement. Grade C fistula are most severe resulting in significant morbidity and/or death.
Time Frame	3 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Secretin	Saline
Arm/Group Description	Stimulate pancreatic secretion Secretin: Drug to stimulate pancreatic secretion	Placebo should not stimulate the pancreas to release its fluids Placebo
Measure Participants	87	83
Biochemical Leak	25 28.7%	16 19.3%
Grade B Fistula	3 3.4%	5 6%
Grade C Fistula	0 0%	0 0%

2. Secondary Outcome

Title	Number of Participants With Intra-operative Intervention, Subsequent Biochemical Leak or B/C Fistula After Drug Administration
Description	Following the administration of Secretin or Placebo intraoperatively, the surgeon will have the opportunity to evaluate the anastomosis to determine if there is ongoing leak. If there is ongoing leak, then the surgeon will be able to treat the leak intra-operatively prior to operative closure. In those patients in whom an intervention was performed, they were subsequently evaluated to determine if they developed a biochemical leak or grade B/C fistula.
Time Frame	Through completion of intra-operative intervention and subsequent biochemical leak, B/C Fistula up to 30 days post-operatively

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Secretin	Saline
Arm/Group Description	Stimulate pancreatic secretion Secretin: Drug to stimulate pancreatic secretion	Placebo should not stimulate the pancreas to release its fluids Placebo
Measure Participants	87	83
Intervention	8 9.2%	3 3.6%
Subsequent Biochemical Leak	8 9.2%	2 2.4%
Subsequent B/C Fistula	0 0%	1 1.2%

3. Secondary Outcome

Title	Length of Hospitalization
Description	Surrogate marker for operative success
Time Frame	Duration of study - average 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Secretin	Saline
Arm/Group Description	Stimulate pancreatic secretion Secretin: Drug to stimulate pancreatic secretion	Placebo should not stimulate the pancreas to release its fluids Placebo
Measure Participants	87	83
Mean (Standard Deviation) [Days]	10.3 (6.5)	10.2 (5.5)

Adverse Events

Time Frame	Study enrollment until 30 days post-hospital discharge, an average of 45 days
Arm/Group Title	Secretin		Saline
Arm/Group Description	Stimulate pancreatic secretion Secretin: Drug to stimulate pancreatic secretion		Placebo should not stimulate the pancreas to release its fluids Placebo
All Cause Mortality
	Secretin		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/87 (0%)		1/83 (1.2%)
Serious Adverse Events
	Secretin		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/87 (17.2%)		32/83 (38.6%)
Cardiac disorders
Hypotension	0/87 (0%)		2/83 (2.4%)
Gastrointestinal disorders
Gastroparesis	0/87 (0%)		1/83 (1.2%)
Pancreatitis	0/87 (0%)		2/83 (2.4%)
Hepatobiliary disorders
Bile Leak	1/87 (1.1%)		3/83 (3.6%)
Infections and infestations
Infection - other	1/87 (1.1%)		2/83 (2.4%)
Superficial surgical site infection	1/87 (1.1%)		6/83 (7.2%)
Surgical and medical procedures
Deep Surgical Site Infection	3/87 (3.4%)		3/83 (3.6%)
Hemorrhage	6/87 (6.9%)		10/83 (12%)
Hernia	0/87 (0%)		1/83 (1.2%)
Other	3/87 (3.4%)		2/83 (2.4%)
Other (Not Including Serious) Adverse Events
	Secretin		Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/87 (41.4%)		23/83 (27.7%)
Cardiac disorders
Hypertension	7/87 (8%)		2/83 (2.4%)
Hypotension	10/87 (11.5%)		5/83 (6%)
Gastrointestinal disorders
Gastroparesis	2/87 (2.3%)		1/83 (1.2%)
Hepatobiliary disorders
Chyle Leak	3/87 (3.4%)		1/83 (1.2%)
Infections and infestations
Infection - other	1/87 (1.1%)		3/83 (3.6%)
Surgical and medical procedures
Deep Surgical Site Infection	1/87 (1.1%)		0/83 (0%)
Hemorrhage	3/87 (3.4%)		5/83 (6%)
Hernia	0/87 (0%)		1/83 (1.2%)
Superficial Surgical Site Infection	6/87 (6.9%)		4/83 (4.8%)
Other	3/87 (3.4%)		1/83 (1.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.