Lumen Apposing Metal Stents vs Double Pigtail Stents

Study Overview
=================
Brief Summary
-----------------
While the majority of patients with acute pancreatitis suffer a mild and uncomplicated course of disease, up to 20% develop a more severe course with development of pancreatic and/or peripancreatic necroses. With time, these necroses become encapsulated with a well-defined inflammatory wall, so called walled-off necroses (WON). Up to 30% of WONs become infected, which prolongs the length of hospital stay, increases morbidity and mortality significantly, and generally requires an invasive intervention. During the last decade, minimally invasive therapies consisting of percutaneous and endoscopic, transluminal drainage followed, if necessary, by percutaneous or endoscopic necrosectomy, have replaced open surgery as the standard treatment resulting in better patient outcomes. The investigators have for nearly two decades been practicing an endoscopic step-up approach as standard treatment for infected WON. Recently, lumen apposing metal stents (LAMS) have been introduced for the treatment of pancreatic fluid collections. The stent is fully-covered and shaped with two bilateral anchor flanges with a saddle in between. A dedicated through-the-scope delivery system, where the tip serves as an electro cautery device enables extra-luminal access and deployment of the stent. Initial results from primarily retrospective case series were promising. However, a recent randomized controlled trial failed to demonstrate superiority in terms of number of necrosectomies needed, treatment success, clinical adverse events, readmissions, length of hospital stay (LOS), and overall treatment costs. Furthermore, a number of serious adverse events with development of pseudoaneurisms probably due to collapse of the cavity have led to alterations in treatment with sequential computed tomography (CT) scans and insertion of double pigtail stents within the metal stent. In that trial, the mean diameter of the treated necroses was limited and in addition, the study was launched before the introduction of a novel 20 mm in diameter LAMS. The investigators hypothesize, that use of a 20 mm LAMS in large caliber WON is superior to the standard double pigtail technique. Aim To compare the use of a novel 20 mm lumen apposing metal stent (LAMS) (Hot Axios, Boston Scientific) with a conventional double pigtail technique for endoscopic transluminal drainage of large (> 15 cm) pancreatic and/or peripancreatic walled-of necrosis (WON).

Official Title
-----------------
EUS-guided Drainage of Large Walled-off Pancreatic Necrosis Using Lumen Apposing Metal Stents or Standard Double Pigtail Technique. A Single-center, Open-label, Randomized, Superiority Trial

Conditions
-----------------
Pancreatitis,Acute Necrotizing

Intervention / Treatment
-----------------
* Device: EUS guided transgastric drainage


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inclusion criteria (all criteria must be fulfilled): Patients with acute, necrotizing pancreatitis and WON exceeding a diameter of 15 cm (measured on contrast-enhanced CT (CECT); see details on imaging tests below). WON is defined based on the revised Atlanta criteria as a mature, encapsulated pancreatic or peripancreatic necrosis with a well-defined inflammatory wall[12]. Imaging test(s) must be done within 1 week before the index drainage procedure. Debut of pancreatitis must be within 3 months before the index drainage procedure. One or more indication(s) for endoscopic, transmural drainage must be established: 1. Confirmed or suspected infection.1 2. Severe intraabdominal hypertension or abdominal compartment syndrome. 3. Persisting abdominal pain, early satiety, or general discomfort. 4. Obstruction of the GI or biliary tract. 5. Leakage of pancreatic juice, e.g. ascites or pleural effusion. 3. Preoperatively, the WON must be considered eligible for endoscopic, transgastric drainage with both conventional double pigtail and LAMS technique. Distance between the gastric wall and WON must not exceed one cm and there must be no major interposed vessels. Infection in WON: Confirmed infected necrosis is defined as a) positive culture from WON obtained by fine- needle aspiration prior to or at the first drainage procedure or b) presence of gas in WON on CECT prior to drainage with no earlier puncture/drainage and no signs of perforation to the GI tract. Infected necrosis is suspected when a patient with WON present with clinical signs of persistent sepsis without other causes of infection. Exclusion Criteria: Patients under the age of 18. Pregnancy. Known or suspected malignant disease. Pancreatitis secondary to trauma or surgical intervention. Chronic pancreatitis. Collections that may only be drained from the duodenum. Previous surgical or endoscopic drainage or necrosectomy.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A single-center, open-label, randomized, superiority trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Double pigtail<br>Plastic stent group EUS-guided drainage shall be performed as follows: a) Puncture of WON with a 19 GA Access needle (Cook Medical), b) aspiration of fluid in WON for microbiological assessment, c) insertion of guidewire (0.035 inch, 450 cm, Dreamwire (Boston Scientific), d) creation of transmural tract with needle knife over the guidewire, e) dilatation of tract to a diameter of 15 mm with dilation balloon (EZDilate, Olympus), f) insertion of two 7-Fr/6 cm double pigtail stents and a 7-Fr naso-cystic irrigation catheter. | Device: EUS guided transgastric drainage<br>* Whenever possible, randomisation and intervention shall be postponed until 4 weeks after onset of pancreatitis in line with international guidelines. All procedures in this study shall be performed by three experienced endoscopists (PNS, EFH, SN), who all have an extensive experience in endoscopic ultrasound (EUS-) guided drainage of pancreatic collections and the use of self-expanding stents. They have together performed more than 300 endoscopic, transmural drainage and debridement procedures in patients with WON since 2005. Endosonography-guided, transgastric drainage of the WONs shall be performed using a curve-linear echoendoscope (endoscope: Olympus GF-UCT180; ultrasound scanner: Hitachi Arietta 850 or Olympus EU-ME2). All collections shall be treated by single tract transmural cystogastrostomy (single-gate technique). T<br>|
| Experimental: Lumen apposing metal stent<br>LAMS shall be the Hot AXIOS stent with electrocautery-enhanced delivery system (Boston Scientific). The stent is a through-the-scope, fully covered, self-expandable metal stents with a diameter of 20 mm and a length of 10 mm. Before placement of the LAMS, the WON shall be punctured with a 19 GA Access needle (Cook Medical) and fluid in WON aspirated for microbiological assessment. Thereafter the LAMS shall be placed as follows: After directly puncturing the WON using the electrocautery tip (without the use of a guidewire to assist in stent insertion), the delivery catheter is advanced into the WON and the distal flange is deployed under EUS-guidance. The proximal flange is then released under EUS guidance or endoscopic view. After placement of the LAMS, a 7-Fr/4cm double pigtail and a 7-Fr nasocystic irrigation catheter shall be placed through the LAMS. | Device: EUS guided transgastric drainage<br>* Whenever possible, randomisation and intervention shall be postponed until 4 weeks after onset of pancreatitis in line with international guidelines. All procedures in this study shall be performed by three experienced endoscopists (PNS, EFH, SN), who all have an extensive experience in endoscopic ultrasound (EUS-) guided drainage of pancreatic collections and the use of self-expanding stents. They have together performed more than 300 endoscopic, transmural drainage and debridement procedures in patients with WON since 2005. Endosonography-guided, transgastric drainage of the WONs shall be performed using a curve-linear echoendoscope (endoscope: Olympus GF-UCT180; ultrasound scanner: Hitachi Arietta 850 or Olympus EU-ME2). All collections shall be treated by single tract transmural cystogastrostomy (single-gate technique). T<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of necrosectomies | Number of debridement procedures (endoscopic and video-assisted) needed throughout the disease course. | Through study completion, an average of 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of endoscopic procedures | Number of endoscopic procedures (drainage (including redilatation) and debridement) | Through study completion, an average of 6 months | 
| Total number of drainage and debridement procedures (radiological, endoscopic, and surgical) |  | Through study completion, an average of 6 months | 
| Number of days from index drainage procedure until removal of naso-cystic catheter |  | Through study completion, an average of 6 months | 
| Duration of drainage and debridement procedures | Duration of drainage and debridement procedures (index and cumulated). It will be in minutes | Through study completion, an average of 6 months | 
| Length of hospital stay from the index drainage procedure | Days of hospital stay from the index drainage procedure | Through study completion, an average of 6 months | 
| Length of ICU stay | Days in the ICU | Through study completion, an average of 6 months | 
| Resolution of pre-interventional systemic inflammatory response syndrome (SIRS) (sepsis) | Restoration of normal blood pressure, temperature, heart rate, inspiratory rate, and white blod cell count | Through study completion, an average of 6 months | 
| New onset episodes of culture verified bacteremia |  | Through study completion, an average of 6 months | 
| Occurrence of splanchnic vein thrombosis (portal-, splenic-, or superior mesenteric vein) |  | Through study completion, an average of 6 months | 
| Need for tube feeding (naso-gastric or naso-jejunal) or parenteral nutrition |  | Through study completion, an average of 6 months | 
| CRP-area under curve (AUC) from the index drainage procedure until discharge from hospital |  | Though the hospital stay, an average of 6 months | 
| Number of adverse events according to the ASGE lexicon and Clavien-Dindo. | Specific adverse events and grouped by severity | Though the hospital stay, an average of 6 months | 
| Mortality | The rate mortality compared between the two study groups | Though the hospital stay, an average of 6 months | 
| Exocrine and endocrine insufficiency | The unset of diabetes and Steatorré | Though the hospital stay, an average of 6 months | 
| Total treatment costs. | In euros and dollars | Through study completion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Walled of necrosis, Endoscopic drainage, Lumen apposing metal stents