Comparing Fully Covered, Self Expanding Metal Stent (FCSEMS) and Plastic Stents for EUS- Guided Drainage of WON
Comparing Fully Covered, Self Expanding Metal Stent (FCSEMS) and Plastic Stents for EUS- Guided Drainage of WON
This is a multi-center, single-blinded, randomized trial comparing AXIOS FCSEMS (Fully
 Covered Self Expanding Metal Stent) and plastic stents for EUS (Endoscopic Ultrasound)-guided
 management of infected and/or symptomatic WON (Walled Off Necrosis).

 Patients will be randomized to either FCSEMS or plastic stents for EUS-guided drainage of WON
 in a 1:1 manner. Following EUS-guided drainage patients in both groups will be assessed pre-
 procedure, pre -discharge, weeks 1, 6 and months 3, 6, 12 and 24 months. Information will
 also be collected from any subsequent hospital admissions related to their walled-off
 necrosis.
Consenting eligible patients will sign an IRB (Institutional Review Board)-approved, written
 informed consent to verify their willingness to participate in this study. Informed consent
 will be obtained on the day of their scheduled endoscopic drainage procedure and will occur
 at the time of consent to undergo the endoscopic drainage procedure (standard of care).
 Consent for the study will be obtained by one of the participating endoscopists and/or a
 research assistant. Subjects will receive a copy of the signed and dated informed consent
 document. Original informed consent documents will be maintained on-file at each
 participating center and will be made available for review upon request by coordinating
 center team or IRB, and/or any additional oversight organizations. A note may be made in the
 subject's hospital chart regarding participation in the research study. Once consented and
 enrolled into the trial, subjects will be issued a unique code to be used on data collection
 forms and other research records throughout the duration of the trial.

 Preparation, Imaging and Endoscopic Procedures:

 Patients on anti-platelet therapy or anticoagulation

 1. Warfarin is to be stopped prior to the procedure per institutional guidelines..

 2. Patients on heparin:

 1. Subcutaneous low molecular weight heparin (LMWH) is held for 12 hours and restarted
 the day after the procedure

 2. Intravenous heparin drip is stopped per institutional guideline prior to the
 procedure and restarted 12 hours after the drainage procedure

 3. Aspirin can be continued until the day of the procedure

 4. Clopidogrel and other anti-platelet agents are to be stopped per institutional
 guidelines prior to the procedure and restarted the day after the procedure. In patients
 with placement of drug-eluting stents within one year, the risk of cessation of
 clopidogrel will have to be weighed against the risk of bleeding during the drainage
 procedure. In that case, cardiology may be consulted so that the best course of action
 can be taken.

 Imaging prior to EUS-guided drainage

 1. MRI (Magnetic Resonance Imaging) / MRCP (Magnetic Resonance Cholangiopancreatography)
 with gadolinium will be performed in all patients to assess the WON. In patients with
 contraindications to MRI, a CECT ( Contrast Enhanced, Computed Tomography)
 abdomen/pelvis will be obtained instead. In patients with contraindication to both
 MRI/MRCP and intravenous iodinated contrast (such as history of anaphylactic reaction to
 iodinated contrast agents or renal impairment with eGFR < 30 mL/min/1.73m2), a
 non-contrast enhanced CT will be performed. All imaging will be interpreted by the
 designated GI/abdominal radiologist at each participating center and also by an
 appointed multidisciplinary panel to determine suitability for inclusion in the study.

 2. In addition to MRI/CT, EUS will be utilized at the time of the drainage procedure in the
 final determination of the percentage of pancreatic necrosis.

 3. ERCP (Endoscopic Retrograde Cholangiopancreatography) will not be mandatory prior to
 EUS-guided drainage as the incidence of disconnected pancreatic duct syndrome (DPDS) is
 high and the placement of a pancreatic duct stent is unlikely to be helpful in this
 case.

 Endoscopic Drainage

 1. Intravenous antibiotic (e.g. ciprofloxacin, levofloxaen or augmentin) is administered on
 the day of the procedure. Oral antibiotics will be continued for ten days following
 drainage.

 2. All procedures are performed under general anesthesia.

 3. One drainage site is created in all WON, regardless of size or stent type.

 4. Percutaneous drainage is not undertaken prior to EUS-guided drainage.

 5. Insertion of plastic stents:

 1. WON is first identified using EUS, and punctured using a 19G needle. 20cc of the
 pancreatic fluid is aspirated and sent for CEA, amylase, cell count, gram stain and
 culture with sensitivities. A 0.025 or 0.035 inch guidewire is inserted into the
 WON through the FNA (Fine Needle Aspirate) needle. A transmural tract is created
 using an ERCP catheter (with the use of a needle knife catheter ± cautery if
 needed), and then dilated using a 12-13.5-15mm CRE balloon to a maximum size of
 15mm if technically possible. Three 7Fr OR two 10Fr plastic stents are inserted
 through the transmural tract into the WON cavity.

 2. A nasocystic catheter is placed into the WON through the plastic stent and
 irrigated every six hours using 250 cc of normal saline for 48 hours. The patient
 will remain in-patient for irrigation of the nasocystic catheter. If an attempt at
 nasocystic catheter fails the endoscopist will attempt to lavage the cystic cavity
 with 2L of saline at that time with 2L of sterile water.

 3. If placement of the nasocystic catheter and lavage fails and/or is not deemed to be
 safe, this will be documented and no further action is taken.

 6. Insertion of AXIOS FCSEMS:

 1. WON is first identified using EUS and punctured using a 19G needle. Enough fluid is
 aspirated to send for CEA, amylase, cell count, gram stain and culture with
 sensitivities.

 2. A 0.025 or 0.035 inch guidewire is inserted into the WON through the FNA needle. A
 transmural tract is created using ERCP dilation catheters or electrocautery devices
 ( needle knife catheter or Hot Axios cautery if needed) as described below. The
 catheter-based stent delivery system with a 15mm AXIOS stent mounted onto it is
 inserted into the endoscope, and introduced into the WON cavity either: 1) after
 dilation with endoscopic dilators (4-5-7 French/5-7-10 French push dilators, 4mm,
 or 6mm balloons) or 2) using electrocautery mounted on the stent system ("Hot
 Axios"). The stent should be positioned so that it lies within both the WON and
 enteric lumen. The stent is then deployed so that one flange of the stent is
 located within the WON cavity and the other flange is located within the enteric
 lumen. The Axios stent is then dilated to at least 13.5-15mm following deployment
 using a 12-15mm balloon.

 3. An attempt at irrigation/lavage of the WON cavity in the endoscopy unit immediately
 following stent deployment using 2L of normal saline should be performed. This can
 be done using a forward viewing gastroscope or endoscopic accessories (push
 dilation catheters, balloon catheters etc.).

 7. Direct endoscopic necrosectomy will not be performed in the same session as the initial
 stent placement.

 8. The following information is collected at the time of initial endoscopic procedure:

 1. Location and size of collection by EUS measurements (two perpendicular
 measurements)

 2. Intraprocedure complications (such as bleeding, pneumoperitoneum, perforation,
 hemodynamic instability)

 3. Procedure duration

 i. Initial procedure (start time: advancement of the endoscope into the patient; end
 time: withdrawal of the echoendoscope, gastroscope or duodenoscope from the patient at
 the end of the procedure)

 Follow-up Procedures:

 Post-procedure management:

 1. Oral antibiotics will be administered for a total of ten days pending the results of
 fluid gram stain and culture. Antimicrobial therapy will thereafter be altered based on
 fluid culture results as indicated.

 2. All patients will be admitted for no less than 48 hours for observation after the index
 endoscopic procedure.

 3. Enteral nutrition will be commenced within 48 hours of the procedure via nasogastric
 tube, PEG-J (Percutaneous endoscopic gastrostomy tube with a jejunal extension),
 nasojejunal tube or surgical/endoscopic jejunostomy or through the prompt transition to
 oral diet unless contraindicated. Route of enteral nutrition support will be determined
 by the treating physician.

 4. In the plastic stent group, the WON is irrigated using 250cc of normal saline every six
 hours for total duration of 48 hours. The nasocystic catheter is removed after 48 hours.

 At 48-96 hours post-procedure:

 1. MRI/CECT (if contraindication to MRI) is obtained if any of the following criteria are
 met:

 a. Persistent symptoms of abdominal pain, gastric outlet obstruction and/or failure to
 advance diet b. Ongoing SIRS (Systemic Inflammatory Response Syndrome) /Sepsis c.
 Persistent organ failure

 2. If the above repeat MRI/CECT fail to show resolution of WON (defined as ≥50% decrease in
 volume), a repeat intervention is performed

 3. The type of repeat intervention performed is to be determined by the treating physician
 and can include:

 1. Direct endoscopic necrosectomy (DEN) in unilocular collection with significant
 solid component

 2. Creation of a second drainage site and/or DEN in multi-loculated/large collection
 without a significant solid component

 3. Placement of interventional radiology-guided percutaneous drain in collections not
 accessible via the stomach/duodenum

 4. Repeat interventions are performed at a frequency determined by the treating physician
 until the volume of WON has decreased ≥ 50% with clinical improvement, up to maximum of
 three sessions.

 5. If there is still inadequate response to treatment (as defined above) after three
 endoscopic transmural drainage procedures using the designated stent type (i.e.
 procedure #1=stent insertion, procedure #2-3= insertion of more stents into a second
 drainage site ± direct endoscopic necrosectomy ± percutaneous drain insertion), the
 patient is defined as "endoscopic treatment failure". These patients will be referred
 for minimally invasive surgical debridement of WON.

 6. Procedures #2 and 3 will also be undertaken as described above for patients returning to
 the hospital in the period following discharge after index procedure.

 Pre-discharge:

 Following information is obtained prior to discharge:

 1. Symptoms:

 a. Pain b. Nausea/vomiting c. Malaise d. Oral intake (liquid diet, solid diet, duration
 of tolerance to po intake)

 2. Adverse events

 3. Need for repeat endoscopic procedures: percutaneous drain placement, surgery

 4. VAS pain score

 At Week 1: (+ or- 2 days)

 Telephone calls are made to all patients to collect the following information:

 1. Symptoms

 2. Adverse events

 3. VAS pain score

 4. SF-36

 At Week 6: (+ or -7 days)

 1. Repeat MRI/MRCP with gadolinium (or CECT if MRI contraindicated) is performed to
 reassess the size of WON and to look for disconnected pancreatic duct syndrome (DPDS):

 1. If DPDS is present on MRI/CT, no ERCP is done

 2. If DPDS if not present on MRI/CT, ERCP is performed the following day to confirm
 patency of the pancreatic duct. If a partial pancreatic duct leak is present on
 ERCP, a transpapillary stent is placed during the same endoscopic session. Repeat
 ERCP with stent exchange is to be performed at the discretion of the endoscopist.

 2. If the WON is < 10% of its original size (defined as treatment success),:

 a. All transmural stents are removed if the main pancreatic duct (MPD) is intact.

 b. If the MPD is disconnected, all but one plastic stent is removed. A single double
 pigtail plastic stent will be left in place indefinitely. In patients with FCSEMS and
 DPDS, the metal stent is removed and a single 7Fr double pigtail plastic stent is placed
 instead and left in place indefinitely. FCSEMS is replaced with double pigtail plastic
 stents in this group as thus far the long-term sequelae of inserted AXIOS stents are not
 known, including the risk of stent migration.

 3. If at or during the first 6 weeks after the initial drainage procedure, there no
 resolution of WON and/or persistent symptoms repeat interventions are performed.

 4. The type of repeat intervention performed is to be determined by the treating physician
 with suggestions listed below. These can include:

 1. Direct endoscopic necrosectomy (DEN) in unilocular collection with significant
 solid component

 2. Creation of a second drainage site and/or DEN in multi-loculated/large collection
 without a significant solid component

 3. Placement of interventional radiology-guided percutaneous drain in collections not
 accessible via the stomach/duodenum

 4. Referral for minimally invasive surgical debridement of WON. Surgical intervention
 should be considered in patients with significant, ongoing debilitating symptoms.

 5. MRI/MRCP is then again repeated 6 weeks following the second round of drainage
 procedures to check for WON resolution

 6. If there is no resolution of WON following the second endoscopic drainage, repeat
 intervention(s) as outlined in 4) is performed.

 7. MRI/MRCP is then again repeated 6 weeks following the third drainage to check until WON
 resolution

 8. If there is no resolution of WON following the third endoscopic drainage, the patient
 must be referred for minimally invasive surgical necrosectomy

 9. Documentation of symptoms or adverse events

 10. Admissions

 11. VAS score

 12. SF-36 questionnaire Any subsequent admissions (related to the Walled Off- Necrosis)

 The following information will be collected in patients hospitalized with recurrent symptoms:

 1. Symptoms

 2. Adverse events

 3. VAS pain score or admission recorded pain score if at any outside hospital

 4. Need for subsequent endoscopic, percutaneous or surgical procedures for WON

 5. Duration of Hospital stay

 At Month 3, 6, 12, 24: (+ or - 14 days)

 Telephone calls are made to all patients to gather information on the outcome measures:

 1. Documentation of symptoms or adverse events

 2. Admissions

 3. VAS score

 1) SF-36 questionnaire ( Months 6, 12 and 24 only)

 5) MRI/MRCP or CT scan at 6 months in patients with initial treatment success to determine
 rate of WON recurrence
Inclusion Criteria:

 1. WON diagnosed on contrast-enhanced dual phase CT abdomen/pelvis (CECT) or MRI with
 gadolinium (seen as a fluid collection in the setting of documented pancreatic
 necrosis that contains necrotic material and encased within a well-defined tissue
 layer)

 2. All WON centered within the pancreatic/peri-pancreatic space not requiring
 percutaneous drainage, ≥ 6cm, located within 2cm of the enteric wall, not extending
 into the flanks or pelvis

 3. WON with single loculation, with no extension into the flanks, pelvis or into the root
 of the small bowel mesentery. Collections should have an estimated solid component of
 = or >25% based on cross sectional imaging and/or endosonographic evaluation of the
 collection at the time of study procedure.

 4. Suspected/confirmed infected WON (defined as temp ≥ 100.5°F, serum WBC ≥ 15x199/L,
 positive blood cultures or positive Gram stain/culture of aspirated necrotic material)
 and/or

 5. Symptomatic WON (defined as abdominal pain, gastric/intestinal/biliary outlet
 obstruction resulting in nausea, vomiting, early satiety, jaundice, or persistent
 malaise) at a time interval of ≥ 4 weeks from attack of acute pancreatitis complicated
 by pancreatic necrosis

 6. Documented history of acute or chronic pancreatitis

 a) Acute pancreatitis is diagnosed if 2 of the following 3 criteria are met: i)
 Abdominal pain characteristic of acute pancreatitis ii) Serum lipase/amylase ≥ x3
 upper limit of normal iii) Characteristic radiological findings of acute pancreatitis
 on CECT/MRI/US abdomen, such as homogeneous enhancement of pancreatic parenchyma,
 standing of peripancreatic fat (1) b) Chronic pancreatitis is diagnosed if
 characteristic radiological changes are seen on CT/MRI with MRCP (such as pancreatic
 atrophy, dilated pancreatic duct, pancreatic calcification) (11) or EUS (≥5/9 of
 Rosement criteria) (12)

 7. Able to undergo general anesthesia

 Exclusion Criteria:

 1. Age < 18 years

 2. Unable to obtain consent for the procedure

 3. Pregnancy

 4. Irreversible coagulopathy: INR > 1.5, platelets < 50 x 109/L

 5. Use of anticoagulants that cannot be discontinued for the procedure

 6. Unable to tolerate general anesthesia

 7. WON with ≥ 3 loculations

 8. WON that is not accessible for EUS-guided drainage

 9. Percutaneous drainage of WON is required or performed prior to EUS-guided drainage

 10. Prior endoscopic, percutaneous or surgical drainage procedure(s) for
 pancreatic/peri-pancreatic fluid collections.

 11. Contraindication to endoscopic drainage: Gastrectomy with Billroth II, gastric
 bariatric surgery, prior pancreatic surgery, prior esophagectomy, cirrhosis.