Endoscopic Necrosectomy Versus Step-up Endoscopic Intervention

Pancreatic Necrosis Clinical Trial

— DESTIN  

Official title:

A Randomized Trial Comparing Direct Endoscopic Necrosectomy vs. Step-up Transluminal Endoscopic Interventions in Infected Necrotizing Pancreatitis (DESTIN)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04113499
• Other study ID #: 1438851
• Status: Completed
• Phase: N/A
• Start date: November 27, 2019
• Est. completion date: April 25, 2022

Study information

• Verified date: July 2023
• Source: AdventHealth
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is to compare clinical outcomes between patients undergoing immediate endoscopic necrosectomy compared to step-up endoscopic interventions in patients undergoing endoscopic therapy for infected necrotizing pancreatitis.

Description:

Acute pancreatitis has an annual incidence of 13-45 cases per 100,000 persons and is one of the most common gastrointestinal disorders requiring hospitalization worldwide. It leads to over a quarter of a million hospital admissions annually in the United States, and inpatient costs exceeding 2.5 billion US dollars. Pancreatic necrosis occurs as a consequence of severe acute pancreatitis in approximately 20% of patients. It can mature into a contained necrotic collection, typically four weeks into the disease course. With intense conservative management, including nutritional and intensive care support when required, the collection may resolve without intervention. However, a persistent collection with pain, gastric outlet, intestinal or biliary obstruction, new-onset or persisting organ failure, persistent unwellness or infection is associated with a mortality of 15-20%, and requires necrosectomy and drainage. Without intervention, infected necrosis ultimately leads to death in nearly every patient. Recently, there has been a shift away from surgical debridement (necrosectomy) towards minimally-invasive endoscopic methods in the treatment of necrotizing pancreatitis. Endoscopic management involves creation of a fistula between the enteric wall and necrotic collection under the guidance of endoscopic ultrasound [EUS] with subsequent placement of a stent to allow drainage of the necrotic material. Endoscopic transenteral drainage of necrotic collection is associated with favorable outcomes, with treatment success rates reported in the range of 45-70%. Endoscopic necrosectomy, with the additional technique of extraction of necrotic material under direct endoscopic visualization has increased rates of treatment success to greater than 80%. However, there are currently scant data on the optimal timing of endoscopic necrosectomy. In a retrospective study, performing endoscopic necrosectomy at the time of the initial EUS-guided drainage of the necrotic collection was associated with a significantly lower number of necrosectomy sessions compared to performing endoscopic necrosectomy one week after drainage. The aim of this randomized trial is to compare clinical outcomes between patients undergoing immediate endoscopic necrosectomy (direct endoscopic necrosectomy) compared to step-up endoscopic interventions in patients undergoing endoscopic therapy for infected necrotizing pancreatitis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: April 25, 2022
• Est. primary completion date: April 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. The subject (or when applicable the subject's LAR) is capable of understanding and complying with protocol requirements

2. The subject (or when applicable the subject's LAR) is able to understand and willing to sign an informed consent form prior to the initiation of any study procedures

3. Males or females = 18 years of age

4. Necrotic collection diagnosed on MRI or CT abdomen/pelvis (seen as a fluid collection in the setting of documented pancreatic necrosis that contains necrotic material and encased within a partial or complete wall)

5. Necrotic collection of any size with = 33% of solid/necrotic component and any no. of loculations, located within the pancreatic/peri-pancreatic space

6. Necrotic collection visualized on EUS and amenable to EUS-guided drainage

7. Suspected/confirmed infected necrotic collection. Infected necrosis is defined by the presence of gas in the necrotic collection on cross-sectional imaging or positive culture of necrotic tissue obtained preprocedure or at first intervention. Infected necrosis is also suspected when sepsis is persistent or in the presence of ongoing clinical deterioration.

8. Documented history of acute pancreatitis Acute pancreatitis is diagnosed if 2 of the following 3 criteria are met

1. Abdominal pain characteristic of acute pancreatitis

2. Serum lipase/amylase = x3 upper limit of normal

3. Characteristic radiological findings of acute pancreatitis on CECT/MRI/US abdomen, such as homogeneous enhancement of pancreatic parenchyma, standing of peripancreatic fat

9. Able to undergo general anesthesia

Exclusion Criteria:

1. Females who are pregnant or lactating. Pregnancy for females of childbearing potential will be determined by routine preoperative urine or serum HCG testing.

2. Irreversible coagulopathy (INR >1.5, thrombocytopenia with platelet count <50,000/mL)

3. Has surgically altered gastrointestinal anatomy such as but not limited to Billroth II, Roux-en-Y, gastric bypass

4. Age < 18 years

5. Unable to obtain consent for the procedure from either the patient or LAR

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

7. Unable to tolerate general anesthesia

8. Necrotic collection that is not accessible for EUS-guided drainage

9. Percutaneous drainage of the necrotic collection is required or performed prior to EUS-guided drainage

Related Conditions & MeSH terms

• Necrosis
• Necrosis Pancreas
• Pancreatic Necrosis
• Pancreatitis, Acute Necrotizing

Intervention

Procedure:
• Direct Endoscopic Intervention
The necrotic collection is first identified using a linear echoendoscope. A Hot AXIOS stent is utilized in all patients for EUS-guided drainage of the necrotic collection. The necrotic material is sent for gram stain and culture with sensitivities. For endoscopic necrosectomy, in patients allocated to direct endoscopic necrosectomy group, endoscopic necrosectomy is performed during the same session as the index endoscopic drainage. It is performed using a therapeutic gastroscope and various accessories (see below for further details) for 90 to 120 minutes.
• Step-up Endoscopic Intervention
The necrotic collection is first identified using a linear echoendoscope. A Hot AXIOS stent is utilized in all patients for EUS-guided drainage of the necrotic collection. The necrotic material is sent for gram stain and culture with sensitivities. In patients allocated to the step-up endoscopic interventions group, endoscopic necrosectomy is not performed at the time of the index intervention, however it is performed when clinically indicated during the follow-up period (6 months from index intervention).

Locations

Country	Name	City	State
United States	Center for Interventional Endoscopy	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AdventHealth

Country where clinical trial is conducted

United States, 

References & Publications (11)

Bang JY, Arnoletti JP, Holt BA, Sutton B, Hasan MK, Navaneethan U, Feranec N, Wilcox CM, Tharian B, Hawes RH, Varadarajulu S. An Endoscopic Transluminal Approach, Compared With Minimally Invasive Surgery, Reduces Complications and Costs for Patients With Necrotizing Pancreatitis. Gastroenterology. 2019 Mar;156(4):1027-1040.e3. doi: 10.1053/j.gastro.2018.11.031. Epub 2018 Nov 16. — View Citation

Bang JY, Hasan MK, Navaneethan U, Sutton B, Frandah W, Siddique S, Hawes RH, Varadarajulu S. Lumen-apposing metal stents for drainage of pancreatic fluid collections: When and for whom? Dig Endosc. 2017 Jan;29(1):83-90. doi: 10.1111/den.12681. Epub 2016 Jun 15. — View 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. — View Citation

Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013 Jan;62(1):102-11. doi: 10.1136/gutjnl-2012-302779. Epub 2012 Oct 25. — View Citation

Beger HG, Rau B, Mayer J, Pralle U. Natural course of acute pancreatitis. World J Surg. 1997 Feb;21(2):130-5. doi: 10.1007/s002689900204. — View Citation

Gardner TB, Chahal P, Papachristou GI, Vege SS, Petersen BT, Gostout CJ, Topazian MD, Takahashi N, Sarr MG, Baron TH. A comparison of direct endoscopic necrosectomy with transmural endoscopic drainage for the treatment of walled-off pancreatic necrosis. Gastrointest Endosc. 2009 May;69(6):1085-94. doi: 10.1016/j.gie.2008.06.061. Epub 2009 Feb 24. — View Citation

Peery AF, Dellon ES, Lund J, Crockett SD, McGowan CE, Bulsiewicz WJ, Gangarosa LM, Thiny MT, Stizenberg K, Morgan DR, Ringel Y, Kim HP, DiBonaventura MD, Carroll CF, Allen JK, Cook SF, Sandler RS, Kappelman MD, Shaheen NJ. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology. 2012 Nov;143(5):1179-1187.e3. doi: 10.1053/j.gastro.2012.08.002. Epub 2012 Aug 8. — View Citation

van Brunschot S, Bakker OJ, Besselink MG, Bollen TL, Fockens P, Gooszen HG, van Santvoort HC; Dutch Pancreatitis Study Group. Treatment of necrotizing pancreatitis. Clin Gastroenterol Hepatol. 2012 Nov;10(11):1190-201. doi: 10.1016/j.cgh.2012.05.005. Epub 2012 May 18. — View Citation

Varadarajulu S, Bang JY, Phadnis MA, Christein JD, Wilcox CM. Endoscopic transmural drainage of peripancreatic fluid collections: outcomes and predictors of treatment success in 211 consecutive patients. J Gastrointest Surg. 2011 Nov;15(11):2080-8. doi: 10.1007/s11605-011-1621-8. Epub 2011 Jul 23. — View Citation

Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology. 2013 Jun;144(6):1252-61. doi: 10.1053/j.gastro.2013.01.068. — View 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of treatment success	Treatment success is defined as the resolution of necrotic collection on CT scan in association with clinical resolution of symptoms at 6-month follow-up	6 months
Secondary	Rate of resolution of pre-intervention systemic inflammatory response syndrome	Assessment of preintervention systemic inflammatory response syndrome & their resolution and measured by yes/no.	72 hours post index procedure
Secondary	Rate of resolution of at least 1 pre-intervention organ failure	Assessment of organ failure following the index procedure and their resolution and measured by yes/no.	72 hours post index procedure
Secondary	Number of re-admissions	Assessing the total number of re-admissions following the index procedure.	6 months
Secondary	Rate of technical success for EUS-guided cystogastrostomy	Technical success for EUS-guided cystogastrostomy defined as completion of endoscopic necrosectomy session as planned without the occurrence of adverse events and measured by yes/no.	24 hours
Secondary	Rate of technical success for endoscopic necrosectomy	Technical success for endoscopic necrosectomy defined as any adverse event occurring as a result of necrotizing pancreatitis and measured by yes/no.	6 months
Secondary	Rate of exocrine pancreatic insufficiency	Rate of exocrine pancreatic insufficiency defined as fecal elastase level < 200µg/g in patients not previously taking pancreatic enzyme supplements	6 months
Secondary	Rate of new onset diabetes	Rate of new onset diabetes defined as new onset elevation in fasting plasma glucose = 126 mg/dL, 2-hour plasma glucose = 200 mg/dL after an oral glucose tolerance test or HbA1c = 6.5%	6 months
Secondary	Number of Procedure-related adverse events	Procedure-related adverse events defined as any adverse event occurring as a result of any endoscopic intervention. The subject will be asked to report and medical records will be reviewed for any adverse events related to the procedure.	6 months
Secondary	Number of Disease-related adverse events	Disease-related adverse events, defined as any adverse event occurring as a result of necrotizing pancreatitis. The subject will be asked to report and medical records will be reviewed for any adverse events related to the procedure.	6 months
Secondary	Post-procedure length of intensive care unit (ICU) stay	Measured in the number of days in the intensive care unit	6 months
Secondary	Total length of hospital stay	Measured in the number of days in the hospital	6 months
Secondary	Overall treatment costs	Overall treatment costs from admission until 6 months post index intervention. All relevant costs pertaining to treatment will be taken into consideration - procedure costs, inpatient hospital stay from date of procedure to discharge, readmissions, medications, materials, anesthesia, pharmacy and imaging studies.	6 months