Internal Biodegradable Stent Versus Non-Stent in Patients at High-Risk of Developing Fistula After Pancreatoduodenectomy

Study Overview
=================
Brief Summary
-----------------
The aim of this randomized controlled study is to compare the efficacy of biodegradable internal pancreatic stenting versus no stenting in patients undergoing pancreatoduodenectomy (PD), focusing on a possible superiority association of the device in preventing clinically relevant postoperative pancreatic fistula (CR-POPF). Patients undergoing PD will be randomized into two arms: arm 1: a biodegradable internal pancreatic stent will be placed at the level of the pancreatic anastomosis arm 2: no pancreatic stent will be placed at the level of the pancreatic anastomosis The rate of occurrence of CR-POPF will be compared between the two arms.

Detailed Description
-----------------
Clinically relevant postoperative pancreatic fistula (CR-POPF) represents the most common complication that can occur after pancreatoduodenectomy (PD). CR-POPF is the main cause of morbidity after PD, being associated with a risk of mortality up to 60%. The placement of external or internal pancreatic stents after PD have been investigated as possible strategies for preventing the development of CR-POPF. However, device displacement has been reported as a common cause of pancreatic stents malfunction. Recently, a novel biodegradable pancreatic stent (ARCHIMEDES™) has been introduced. The device has been specifically designed to reduce the risk of displacement, thus offering a new valuable tool to decrease the rate of CR-POPF after PD. In this randomised, controlled, single-center trial, researchers investigate the possible efficacy of biodegradable internal pancreatic stenting of pancreatic anastomosis in patient undergoing PD versus no stenting, focusing on a possible superiority association for preventing CR-POPF. Participants will be randomised into two arms (Biodegradable stent vs non-stent) based on their intra-operative risk of developing POPF according to the Fistula Risk Score (FRS). The rate of CR-POPF will be compared between the two arms.

Official Title
-----------------
Internal Biodegradable Stent Versus Non-Stent in Patients at High-Risk of Developing Fistula After Pancreatoduodenectomy (BioSteP): a Randomized Controlled Study

Conditions
-----------------
Pancreatoduodenectomy, Clinically Relevant Postoperative Pancreatic Fistula, Internal Biodegradable Pancreatic Stent

Intervention / Treatment
-----------------
* Device: Biodegradable Stent


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥18 Patients who undergo pancreatoduodenectomy (PD) Informed Consent Exclusion Criteria: Previous distal pancreatectomy Patients with intra-operative negligible, intermediate or moderate risk of POPF (fistula risk score < 7)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biodegradable Stent<br>An internal biodegradable pancreatic stent (ArchimedesTM) will be placed at the level of the pancreatic anastomosis in patients undergoing pancreatoduodenectomy. | Device: Biodegradable Stent<br>* A trans-anastomotic biodegradable internal stent (ARCHIMEDES™) will be placed between the main pancreatic duct (MPD) and the enterotomy in the jejunum just after the completion of the posterior suture of duct-to-mucosa. The biodegradable stent will then be shaped according to the angle of the jejunal loop in order to minimise the risk of displacement. The adequate length of the stent will be chosen according to the length of the jejunal loop.<br>|
| No Intervention: Non Stent<br>No stent will be placed at the level of the pancreatic anastomosis in patients undergoing pancreatoduodenectomy. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically Relevant Postoperative Pancreatic Fistula (CR-POPF) | The primary objective of the study is to compare the rate of CR-POPF after PD with duct-to-mucosa pancreatico-jejunostomy (PJ) using biodegradable pancreatic internal stent vs no stent. | from three days after surgery until 3 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically Relevant Postoperative Pancreatic Fistula (CR-POPF) severity | The difference between the two treatment arms in terms of severity of CR-POPF will be assessed. CR-POPF will be classified according to the ISGPS definition into two groups: grade B and grade C. Grade B will be further sub-classified in three categories according to Maggino et al.: grade B1, grade B2, grade B3. | from three days after surgery until 3 months after surgery | 
| Postoperative Morbidity | The difference between the two treatment arms in terms of rate of overall postoperative morbidity as defined by Dindo et al. will be assessed. Additionally the Comprehensive Complication Index will be calculated. Post-pancreatectomy hemorrhage (PPH) and delayed gastric emptying (DGE) will be defined according to ISGPS definitions. | from the date of surgery, up to 3 months | 
| Length of Hospital Stay (LOS) | The difference between the two treatment arms in terms of median LOS will be assessed. Median LOS will be defined by subtracting the date of surgery from the date when the enrolled patients are discharged from the hospital. | from the date of surgery until the date of hospital discharge, assessed up to 3 months | 
| Time to Functional Recovery (TFR) | The difference between the two treatment arms in terms of time to functional recovery (TFR) will be assessed. TFR will be defined by subtracting the date of surgery from the date when participants achieve standardized criteria (tolerance of oral intake, recovery of lower gastrointestinal function, adequate pain control on oral analgesia, ability to mobilise and self-care and no evidence of untreated medical problems). | from the date of surgery until the date of functional recovery, assessed up to 3 months | 
| Quality of Life (QoL) | The difference between the two treatment arms in terms of QoL will be assessed. QoL will be measured in several ways. First, self-reported activity status will be measured using the Duke Activity Status Index (Duke Index, DASI)., a brief questionnaire designed to assess physical function and predict exercise capacity (peak oxygen uptake). Second, generic health related QoL will be measured using the Patient Reported Outcome Measure Information System (PROMIS)-29+2 Profile v2.1 (PROPr), a questionnaire designed to measure self-reported physical, mental and social health and wellbeing. | from the day before surgery until 3 months after surgery | 
| Cost-effectiveness | The difference between the two treatment arms in terms of cost-effectiveness will be assessed. Cost-effectiveness will be estimated by the ration of differences in costs to differences in quality adjusted life years (QALYs) between the two groups of the study. QALYs will be calculated using the preference scores obtained from PROMIS-29+2. To calculate QALYs, the preference scores at 90 days after surgery will be multiplied by 0.25 (which represents 1/4 of the year). Cost of care will be estimated considering resources consumed during hospital stay and use of healthcare resources after hospital discharge. | from the date of surgery, up to 3 months | 
| Stent displacement | The rate of biodegradable rate displacement as detected by postoperative contrast-enhanced computed tomography (CE-CT) performed by 10 days after surgery. A displacement will be defined by the absence of visible trans-anastomotic stent or by its complete dislocation in the jejunum/ileum or colon. | 10 days after surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pancreatic surgery, Pancreatoduodenectomy, CR-POPF, Post operative complications, ARCHIMEDES™