Study of a Lumen- Apposing, Covered, Self-Expanding Metal Stent (Axios™) Versus Multiple Double Pigtail Stents

Study Overview
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Brief Summary
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The present study aims to compare the clinical efficacy and cost effectiveness of the AXIOS™ stent versus the conventional approach using double pigtail plastic stents in the treatment of patients with walled-off pancreatic necrosis.

Detailed Description
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Acute pancreatitis (AP) is responsible for nearly a quarter million hospital admissions annually and will affect around 40 per 100,000 persons per year (1). The majority of patients experience a clinically mild course; however, as many as one in five patients develop a severe illness associated with a high mortality (2). In early phases of the disease, there is an acute inflammatory process that may involve necrosis of the pancreatic or peri-pancreatic tissues (3). There are also delayed complications that may develop locally, usually over a period of weeks, which include the formation of walled-off fluid collections. These are sometimes composed of simple fluid and termed pseudocysts, while in other cases they represent organization and encapsulation of sterile or infected necrosis and are termed walled-off pancreatic necrosis (WOPN) (4). The indication to drain or debride these collections usually depends upon on a number of factors, but principally on whether they are symptomatic, infected, or responsible for other local or systemic complications. The contemporary management strategy for walled-off pancreatic fluid collections has shifted in recent years. Surgery, and even percutaneous catheter drainage, should no longer be considered the initial mainstay of therapy in place of endoscopic drainage for simple pseudocysts (5) (6). In addition there is good evidence to support an endoscopic approach for patients with infected necrosis (7). There are now numerous publications reporting the success of direct endoscopic transmural drainage or necrosectomy (ETD/N) for a variety of indications including infected and sterile walled-off collections (8). The issue that now deserves attention is a matter of selecting the best technique to accomplish ETD/N. The current process involves first creating a cystenterostomy to gain access to the walled-off collection, dilating the tract, and then inserting a drainage device. However, there are a variety of available devices and methods in use for drainage, and to our knowledge, none to date have been directly compared in a randomized controlled trial. The conventional approach involves inserting either a pair or more of plastic double pigtail stents or a self-expanding metal stent (SEMS) through a cystenterostomy: both approaches have limitations, and may require multiple endoscopic sessions before definitive resolution (9). One, the pigtail stents have a narrow lumen (7F-10F) and often migrate or become occluded (10). Two, the SEMS also have a tendency occlude, cause local trauma with bleeding and infection, and migrate, which has led some to also use double pigtails to help anchor the SEMS in place (11) (12). These challenges have led to the innovation of large caliber covered stents with flanges on either end to facilitate apposition of the cyst wall and enteral tissues, preventing migration, and allowing for necrosectomy through their wide lumen. To our knowledge there are at least two designs in production; the AXIOS™ stent and the Nagi stent (13) (14). There is now a fair amount of experience, particularly using the AXIOS™ stent (with or without a novel NAVIX access system) for both WOPN and pseudocysts, with the majority of reports showing it to be safe and effective (15) (16) (17) (18) (19) (20). The device has also been successfully used for novel indications including access and drainage of the gallbladder and an intrathoracic fluid collection (21) (22) (23). The AXIOS™ stent is FDA approved for the indication of draining walled off pancreatic necrosis. The present study aims to compare the clinical efficacy and cost effectiveness of the AXIOS™ stent versus the conventional approach using double pigtail plastic stents in the treatment of patients with walled-off pancreatic necrosis.

Official Title
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Randomized, Multi-Center, Comparative and Cost Effectiveness Study of a Lumen- Apposing, Covered, Self-Expanding Metal Stent (Axios™) Versus Multiple Double Pigtail Stents in the Management of Walled Off Pancreatic Necrosis

Conditions
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Pancreatic Necrosis

Intervention / Treatment
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* Device: AXIOS™ stent
* Device: Double Pigtail Stents


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between 18-80 years old (including patients aged 18 and 80) Subjects capable of giving informed consent Patients carrying the diagnosis or symptomatic sterile or infected walled-off pancreatic necrosis (WOPN) based upon Atlanta Classification (4) ≥ 4cm in largest diameter, deemed to require and amenable to endoscopic transmural drainage with or without necrosectomy by attending gastroenterologist Fluid collection size ≥ 4cm in largest diameter (based on CT, MRI, transabdominal or endoscopic ultrasound within 30days) Fluid collection that is adherent to the stomach/bowel wall allowing for fistula tract creation Fluid collection containing significant amount of necrotic material (defined as >30% of echogenic material by ultrasound/EUS, or necrotic debris by CT/MRI) Exclusion Criteria: Inability to provide written informed consent Contraindications to endoscopic treatment as determined by the gastroenterologist attending Pregnant or nursing mothers Bleeding or coagulation disorder Previous surgical or endoscopic cystogastrostomy/enterostomy or necrosectomy Shock Cystic neoplasms or pancreatic malignancy Pseudocysts Subjects cannot be homeless or incarcerated Age younger than 18 or older than 80 More than one pancreatic/peri-pancreatic fluid collection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AXIOS™ stent<br>1. Arm 1 will undergo EUS-guided cystogastrostomy/enterostomy and placement of the AXIOS™ stent 10-15mm (saddled diameter; choice at the discretion of the treating gastroenterologist) though the tract into the collection cavity, and correct positioning of the inner flange confirmed by EUS prior to deploying within the stomach or duodenum. Necrosectomy will be performed at the discretion of the attending gastroenterologist. Repeat endoscopy will be performed for stent removal at or before 60 days at the discretion of the attending gastroenterologist | Device: AXIOS™ stent<br>* Arm 1 will undergo EUS-guided cystogastrostomy/enterostomy and placement of the AXIOS™ stent 10-15mm (saddled diameter; choice at the discretion of the treating gastroenterologist) though the tract into the collection cavity, and correct positioning of the inner flange confirmed by EUS prior to deploying within the stomach or duodenum.<br>|
| Active Comparator: double pigtail stents<br>2. Arm 2 will undergo EUS-guided cystogastrostomy/enterostomy and placement of multiple double pigtail stents (i.e. ≥2) through the tract into the collection cavity. Necrosectomy will be performed at the discretion of the attending gastroenterologist. Routine repeat treating gastroenterologist for stent removal will not be necessary, but left to the discretion of the attending gastroenterologist. | Device: Double Pigtail Stents<br>* Arm 2 will undergo EUS-guided cystogastrostomy/enterostomy and placement of multiple double pigtail stents (i.e. ≥2) through the tract into the collection cavity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cost Differences | To compare the cost differences of the AXIOS™ stent vs. multiple double pigtail stents in the management of walled-off pancreatic necrosis. | Subject followed for an average of one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Definitive Resolution | 1. To compare the relative efficacy in terms of definitive resolution of walled off pancreatic necrosis using the AXIOS™ stent vs. multiple double pigtail stents. | Subject followed for an average of one year | 
| Number of Endoscopic Sessions | 2. To compare the number of endoscopic sessions required to achieve definitive resolution of walled-off pancreatic fluid necrosis using the AXIOS™ stent vs. multiple double pigtail stents. | Subject followed for an average of one year | 
| Number of Additional Procedures | 3. To compare the number of additional procedures (surgical, percutaneous, or nasocystic) required to achieve definitive resolution of walled-off pancreatic necrosis using the AXIOS™ stent vs. multiple double pigtail stents. | Subject followed for an average of one year | 
| Frequency of Stent Migration | 4. To compare the frequency of stent migration using the AXIOS™ stent vs. multiple double pigtail stents in the management of walled-off pancreatic necrosis. | Subject followed for an average of one year | 
| Number of Participants With Adverse Events | 5. To compare the safety and tolerability of the AXIOS™ stent vs. multiple double pigtail stents in the management of walled-off pancreatic necrosis as assessed by the collected of adverse events over the course of the study, including but not limited to: bleeding, infections, stent migration, surgery and pain. | Subject followed for an average of one year |