Secretin Infusion to Prevent Pancreatic Leaks Following Pancreatic Resection
Condition: Injury of Body of Pancreas
Study type: Interventional
Phase: Phase 2/Phase 3

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.
    

Intervention name(s): Secretin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Drug to stimulate pancreatic secretion
Intervention MeSH terms: Secretin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment