Clinical trial NCT04057846: Lumen Apposing Metal Stents vs Double Pigtail Stents
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pancreatitis,Acute Necrotizing
Keywords: Walled of necrosis
Endoscopic drainage
Lumen apposing metal stents
Lead sponsor: Copenhagen University Hospital, Hvidovre
Sponsor class: OTHER
First posted: 2019-08-15
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A single-center, open-label, randomized, superiority trial
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

Inclusion criteria (all criteria must be fulfilled):

1. Patients with acute, necrotizing pancreatitis and

   1. 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\[12\].
   2. Imaging test(s) must be done within 1 week before the index drainage procedure.
   3. Debut of pancreatitis must be within 3 months before the index drainage procedure.
2. 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:

1. 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.
2. Infected necrosis is suspected when a patient with WON present with clinical signs of persistent sepsis without other causes of infection.

Exclusion Criteria:

1. Patients under the age of 18.
2. Pregnancy.
3. Known or suspected malignant disease.
4. Pancreatitis secondary to trauma or surgical intervention.
5. Chronic pancreatitis.
6. Collections that may only be drained from the duodenum.
7. Previous surgical or endoscopic drainage or necrosectomy.

Primary outcomes:
measure: Number of necrosectomies
timeFrame: Through study completion, an average of 2 year
Secondary outcomes:
measure: Number of endoscopic procedures
timeFrame: Through study completion, an average of 6 months
measure: Total number of drainage and debridement procedures (radiological, endoscopic, and surgical)
timeFrame: Through study completion, an average of 6 months
measure: Number of days from index drainage procedure until removal of naso-cystic catheter
timeFrame: Through study completion, an average of 6 months
measure: Duration of drainage and debridement procedures
timeFrame: Through study completion, an average of 6 months
measure: Length of hospital stay from the index drainage procedure
timeFrame: Through study completion, an average of 6 months
measure: Length of ICU stay
timeFrame: Through study completion, an average of 6 months
measure: Resolution of pre-interventional systemic inflammatory response syndrome (SIRS) (sepsis)
timeFrame: Through study completion, an average of 6 months
measure: New onset episodes of culture verified bacteremia
timeFrame: Through study completion, an average of 6 months
measure: Occurrence of splanchnic vein thrombosis (portal-, splenic-, or superior mesenteric vein)
timeFrame: Through study completion, an average of 6 months
measure: Need for tube feeding (naso-gastric or naso-jejunal) or parenteral nutrition
timeFrame: Through study completion, an average of 6 months
measure: CRP-area under curve (AUC) from the index drainage procedure until discharge from hospital
timeFrame: Though the hospital stay, an average of 6 months
measure: Number of adverse events according to the ASGE lexicon and Clavien-Dindo.
timeFrame: Though the hospital stay, an average of 6 months
measure: Mortality
timeFrame: Though the hospital stay, an average of 6 months
measure: Exocrine and endocrine insufficiency
timeFrame: Though the hospital stay, an average of 6 months
measure: Total treatment costs.
timeFrame: Through study completion
Other outcomes:
Locations:
city: Hvidovre
country: Denmark
facility: Copenhagen University Hospital Hvidovre
state: Capital
Study officials:
References:
citation: van Dijk SM, Hallensleben NDL, van Santvoort HC, Fockens P, van Goor H, Bruno MJ, Besselink MG; Dutch Pancreatitis Study Group. Acute pancreatitis: recent advances through randomised trials. Gut. 2017 Nov;66(11):2024-2032. doi: 10.1136/gutjnl-2016-313595. Epub 2017 Aug 24.
citation: Banks PA, Freeman ML; Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol. 2006 Oct;101(10):2379-400. doi: 10.1111/j.1572-0241.2006.00856.x. No abstract available.
citation: Yan L, Dargan A, Nieto J, Shariaha RZ, Binmoeller KF, Adler DG, DeSimone M, Berzin T, Swahney M, Draganov PV, Yang DJ, Diehl DL, Wang L, Ghulab A, Butt N, Siddiqui AA. Direct endoscopic necrosectomy at the time of transmural stent placement results in earlier resolution of complex walled-off pancreatic necrosis: Results from a large multicenter United States trial. Endosc Ultrasound. 2019 May-Jun;8(3):172-179. doi: 10.4103/eus.eus_108_17.
citation: Schmidt PN, Novovic S, Roug S, Feldager E. Endoscopic, transmural drainage and necrosectomy for walled-off pancreatic and peripancreatic necrosis is associated with low mortality--a single-center experience. Scand J Gastroenterol. 2015 May;50(5):611-8. doi: 10.3109/00365521.2014.946078. Epub 2015 Feb 3.
citation: Bang JY, Navaneethan U, Hasan MK, Sutton B, Hawes R, Varadarajulu S. Non-superiority of lumen-apposing metal stents over plastic stents for drainage of walled-off necrosis in a randomised trial. Gut. 2019 Jul;68(7):1200-1209. doi: 10.1136/gutjnl-2017-315335. Epub 2018 Jun 1.
citation: Kovacevic B, Vilmann P, Karstensen JG. Endoscopic Ultrasonography-Guided Gastrojejunostomies With Lumen-Apposing Metal Stents. Clin Gastroenterol Hepatol. 2017 Mar;15(3):459-460. doi: 10.1016/j.cgh.2016.09.144. Epub 2016 Sep 28. No abstract available.