Islet Autotransplantation in Patients at Very High-risk Pancreatic Anastomosis

Phase 2

Completed

• Conditions: Postpancreatectomy Hyperglycemia
• Interventions: Procedure: Total pancreatectomy with islet autotransplantation; Procedure: Pancreaticoduodenectomy with pancreatic anastomosis

• Registration Number: NCT01346098
• Lead Sponsor: Ospedale San Raffaele

Brief Summary

The goal of the proposal is to demonstrate that, in patients with disease of the pancreatic head with very high-risk of complications of pancreatojejunal reconstruction (soft pancreas and pancreatic duct diameter \<3 mm), total pancreatectomy with islet autotransplantation (IAT) is associated with a lower morbidity (in terms of surgical or medical complications) and mortality compared with pancreaticoduodenectomy and pancreatojejunal anastomosis.

Detailed Description

Complications of the pancreatic anastomosis still represents a significant risk for death after the resection of the pancreatic head. In an effort to decrease morbidity and mortality, the referral of patients who need a pancreaticoduodenectomy to institutions (and surgeons) performing a high volume of this surgical procedure has been championed. Nonetheless, the role of prophylactic medications and the best surgical technique(s) for the removal of the pancreatic head are still debated. However, very few prospective randomized clinical trials have been conducted to compare different surgical techniques.

Our study will address for the first time the role for preemptive total pancreatectomy and IAT in selected patients undergoing pancreaticoduodenectomy that are considered high risk for pancreaticojejunostomy disruption (eg, small pancreatic duct, soft pancreas). The information expected is the identification of total pancreatectomy and the IAT as the standard treatment in a subgroup of patient with pathologies of the pancreatic head at high risk for leakage of pancreatic anastomosis. Ultimately this project will lead to reserve more innovative cell therapy for patients with the highest risk of anastomosis failure reducing pancreatojejunal reconstruction related morbidity and mortality

Study Timeline

• Study Start: 2010-07
• Study First Submitted: 2011-04-29
• Study First Submitted QC: 2011-04-29
• Study First Posted: 2011-05-02
• Primary Completion: 2018-12
• Study Completion: 2019-04
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-02
• Last Update Posted: 2020-11-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Patients >18 years of age
• Ability to provide written informed consent
• Mentally stable and able to comply with the procedures of the study protocol
• Fasting glycaemia <126 mg/dl without glucose-lowering medications.

Exclusion Criteria

• Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial
• Diagnosis of intraductal papillary mucinous cancer, unless the absence of multifocal lesion is demonstrated by endoscopic US
• Presence of multifocal or residual disease at the pancreatic margin.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GROUP B	Total pancreatectomy with islet autotransplantation	At the time of surgery the surgeon will directly assess pancreatic consistency and the pancreatic duct size. In the presence of a soft pancreas and a small duct (diameter \<3 mm), the patient will be randomly assigned to receive either a pancreaticoduodenectomy with pancreatic anastomosis (group A) or a total pancreatectomy with IAT (group B).
GROUP A	Pancreaticoduodenectomy with pancreatic anastomosis	-

Primary Outcome Measures

Name	Time	Method
incidence of complications after pancreatic surgery	90 days from discharge	Complications will be defined and graded according to the Novel Grading System classification ( DeOliveira et al 2006). A special emphasis is given to life-threatening and permanently disabling complications.

Secondary Outcome Measures

Name	Time	Method
Incidence of endocrine and exocrine pancreatic insufficiency	12 months after surgery.	We will assess endocrine pancreatic function by measuring fasting plasma glucose and HbA1c in all patients.; Clinical hallmarks of pancreatic exocrine insufficiency include symptoms of fat malabsorption, such as steatorrhea, weight loss and abdominal pain. Frequency of bowel movements and characteristics of stools will be serially recorded. Fat-soluble vitamins such as A, D, E and K will be measured 12 month after the hospital discharge after the index surgery. Oral pancreatic enzyme supplementation will be prescribed according to the severity of clinical steatorrhea and weight loss.
Incidence of each individual postoperative complication	90 days from discharge	1. death; 2. pancreatic fistula defined according to the International Study Group on Pancreatic Fistula (Bassi C et al 2005); 3. delayed gastric emptying (DGE) defined according to the International Study Group on Pancreatic Fistula (Wente et al 2007); 4. intra-abdominal complications; 5. medical complications

Trial Locations

Locations (1)

IRCCS San Raffaele; 🇮🇹 Milan, Italy