Prophylactic Sphincterotomy in Acute Biliary Pancreatitis Patients Unfit for Surgery

Official title

Prophylactic Endoscopic Sphincterotomy in Patients Unfit for Cholecystectomy After an Acute Biliary Pancreatitis Episode - an Open-label, Two-armed, Randomized Controlled Trial

Overview

This is a prospective, multicenter, open-label, randomized controlled trial designed to evaluate the efficacy and safety of prophylactic endoscopic sphincterotomy (ES) in frail patients unfit for cholecystectomy following an episode of acute biliary pancreatitis (ABP). Eligible patients will be randomized in a 1:1 ratio to either prophylactic ES during the index admission or conservative treatment. The primary endpoint is the time from randomization to the first occurrence of a recurrent pancreatobiliary event within 12 months, including recurrent ABP, cholangitis, choledocholithiasis requiring endoscopic retrograde cholangiopancreatography (ERCP), or cholangiogenic liver abscess. Secondary outcomes include mortality, pancreatobiliary events requiring intensive care unit admission, post-ERCP complications, cholecystitis, and length of hospitalization. A total of 92 patients will be enrolled. The trial will be led by the Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary, and conducted in accordance with Good Clinical Practice.

Interventions

• Procedure Prophylactic endoscopic sphincterotomy
  Participants in this arm will undergo prophylactic endoscopic sphincterotomy performed by experienced endoscopists, with all recommended preventive measures against post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) applied according to international guidelines.

Primary outcome measures

• Recurrent pancreatobiliary events [Time frame: 1 year]

Secondary outcome measures (8)

• Number of participants with recurrent acute biliary pancreatitis, cholangitis, choledocholithiasis, or cholangiogenic liver abscess (individual components of the composite primary outcome) [Time frame: At 3, 6, 9, and 12 months.]
• Length of hospitalization [Time frame: From enrollment to one month.]
• Pancreatobiliary events requiring intensive care unit admission [Time frame: At 3, 6, 9, and 12 months.]
• Mortality associated with pancreatobiliary events [Time frame: At 3, 6, 9, and 12 months.]
• All-cause mortality [Time frame: At 3, 6, 9, and 12 months.]
• Acute cholecystitis [Time frame: At 3, 6, 9, and 12 months.]
• Post-endoscopic retrograde cholangiopancreatography pancreatitis [Time frame: Peri-procedural.]
• Other endoscopic retrograde cholangiopancreatography-related complications [Time frame: Peri-procedural.]

Eligibility criteria

Inclusion criteria

• adult patients (above 18 years)
• naïve papilla
• evidence of AP based on the Atlanta criteria:

• pain in the upper abdomen
• serum amylase or lipase concentration > 3 times the upper limit of normal
• imaging features of acute pancreatitis on abdominal imaging
• high probability of a biliary etiology:

• gallstones or biliary sludge on imaging (any type)
• dilated common bile duct on imaging defined as > 8 mm in patients ≤ 75 years or > 10 mm in patients > 75 years
• abnormal liver enzymes (alanine aminotransferase \[ALT\] two times the upper limit of normal)
• patients unfit for surgery due to the attending physician's decision e.g. American Society of Anesthesiologists (ASA) class ≥ III; severe heart failure with reduced ejection fraction <40%, severe uncontrolled hypertension, chronic kidney disease stage four or five

Exclusion criteria

• previous cholecystectomy
• previous endoscopic sphincterotomy or pancreatobiliary stenting
• ERCP/ES is recommended by the guidelines (3)

• sign of cholangitis
• presence of CBD stone on any imaging
• signs of stone in endoscopic ultrasonography or magnetic resonance imaging in case of abnormal liver enzymes (persistently elevated ALT and aspartate aminotransferase (AST) with less than a 20% decrease over four days) or dilated CBD (defined as above)
• chronic pancreatitis
• estimated life expectancy < 12 months
• ERCP is contraindicated, e.g. the procedure cannot be carried out safely due to the patient's comorbidities or physical status; high risk of bleeding or contraindication of the discontinuation of the anticoagulation therapy.
• ERCP is technically not feasible due to altered anatomy, e.g., total gastrectomy, Roux-en-Y gastric bypass anatomy
• pancreatobiliary malignancy

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Hajibandeh S, Jurdon R, Heaton E, Hajibandeh S, O'Reilly D. The risk of recurrent pancreatitis after first episode of acute pancreatitis in relation to etiology and severity of disease: A systematic review, meta-analysis and meta-regression analysis. J Gastroenterol Hepatol. 2023 Oct;38(10):1718-1733. doi: 10.1111/jgh.16264. Epub 2023 Jun 27. PMID 37366550
• Dedemadi G, Nikolopoulos M, Kalaitzopoulos I, Sgourakis G. Management of patients after recovering from acute severe biliary pancreatitis. World J Gastroenterol. 2016 Sep 14;22(34):7708-17. doi: 10.3748/wjg.v22.i34.7708. PMID 27678352
• Testoni PA, Mariani A, Aabakken L, Arvanitakis M, Bories E, Costamagna G, Deviere J, Dinis-Ribeiro M, Dumonceau JM, Giovannini M, Gyokeres T, Hafner M, Halttunen J, Hassan C, Lopes L, Papanikolaou IS, Tham TC, Tringali A, van Hooft J, Williams EJ. Papillary cannulation and sphincterotomy techniques at ERCP: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. Endoscopy. 2016 J PMID 27299638
• Vazquez-Lglesias JL, Gonzalez-Conde B, Lopez-Roses L, Estevez-Prieto E, Alonso-Aguirre P, Lancho A, Suarez F F, Nunes R. Endoscopic sphincterotomy for prevention of the recurrence of acute biliary pancreatitis in patients with gallbladder in situ: long-term follow-up of 88 patients. Surg Endosc. 2004 Oct;18(10):1442-6. doi: 10.1007/s00464-003-9185-7. Epub 2004 Aug 26. PMID 15791366
• Uomo G, Manes G, Laccetti M, Cavallera A, Rabitti PG. Endoscopic sphincterotomy and recurrence of acute pancreatitis in gallstone patients considered unfit for surgery. Pancreas. 1997 Jan;14(1):28-31. doi: 10.1097/00006676-199701000-00005. PMID 8981504
• da Costa DW, Bouwense SA, Schepers NJ, Besselink MG, van Santvoort HC, van Brunschot S, Bakker OJ, Bollen TL, Dejong CH, van Goor H, Boermeester MA, Bruno MJ, van Eijck CH, Timmer R, Weusten BL, Consten EC, Brink MA, Spanier BWM, Bilgen EJS, Nieuwenhuijs VB, Hofker HS, Rosman C, Voorburg AM, Bosscha K, van Duijvendijk P, Gerritsen JJ, Heisterkamp J, de Hingh IH, Witteman BJ, Kruyt PM, Scheepers JJ PMID 26460661
• Schreurs WH, Juttmann JR, Stuifbergen WN, Oostvogel HJ, van Vroonhoven TJ. Management of common bile duct stones: selective endoscopic retrograde cholangiography and endoscopic sphincterotomy: short- and long-term results. Surg Endosc. 2002 Jul;16(7):1068-72. doi: 10.1007/s00464-001-9104-8. Epub 2002 May 3. PMID 11984690
• Manes G, Paspatis G, Aabakken L, Anderloni A, Arvanitakis M, Ah-Soune P, Barthet M, Domagk D, Dumonceau JM, Gigot JF, Hritz I, Karamanolis G, Laghi A, Mariani A, Paraskeva K, Pohl J, Ponchon T, Swahn F, Ter Steege RWF, Tringali A, Vezakis A, Williams EJ, van Hooft JE. Endoscopic management of common bile duct stones: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy. 2019 PMID 30943551

Identifiers

NCT: NCT07238296 · NNGYK/34436-6/2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗