Rectal NSAIDs With/Without PD Stent for PEP Prevention

Official title

Rectal Non-steroid Anti-inflammatory Drugs With or Without Prophylactic Pancreatic Duct Stent for Prevention of Post-ERCP Pancreatitis: a Multicenter, Randomized, Non-inferiority Trial

Overview

Pancreatitis is the most common and serious complication following post-endoscopic retrograde cholangiopancreatography (ERCP) and is associated with occasional mortality, extended hospital stays, and increased healthcare expenses. Rectal non-steroidal anti-inflammatory drugs (NSAIDs) and pancreatic duct stent (PDS) placement were demonstrated to be effective strategyies to reduce PEP incidences, particlularly in high-risk patients for post-ERCP pancreatitis (PEP). Rectal NSAIDs were easy-to-use and safe, while PDS placement were technically complex and carried higher risks of adverse events. A previous network meta-analysis suggested rectal NSAIDs in combination with PDS placement did not differ from rectal NSAIDs alone in PEP prevention. To invesigate if rectal NSAIDs alone could obivate the need of PDS placement, a recent trial from Elmunzer et al. conducted a randomized trial to investigate if rectal NSAIDs alone was non-inferior to the combination of NSAIDs with PDS in high-risk patients. The trial found that the PEP incidence rate in combination group was significantly lower than that in NSAIDs alone group. However, post-hoc analysis of the study suggested that the combination strategy conferred significant benefits only in high-risk patients with pancreatic duct (PD) wire passage, but not in those with other risk factors. Therefore, we hypothesized that rectal NSAIDs alone may obivate the need of PDS in high-risk patients without PD wire passages. Here, we conducted a multicenter, randomized and non-inferiority trial to investigate whether rectal NSAIDs alone is non-inferior to NSAIDs plus PDS placement in high-risk patients without PD wire passages.

Interventions

• Drug NSAIDs
  All patients without contraindications should receive 100mg rectal indomethacin or diclofenac within 30mins before ERCP procedure
• Device NSAIDs plus PDS
  All patients without contraindications should receive 100mg rectal indomethacin or diclofenac within 30mins before ERCP procedure. When eligibility is met, PDS placement will be performed by ERCP colonoscopists.

Primary outcome measures

• Rate of post-ERCP Pancreatitis [Time frame: 30 days]

Secondary outcome measures (7)

• Rate of mild, moderate or severe PEP [Time frame: 30 days]
• Rate of patients with different severity of pancreatitis evaluated by revised Atlanta criteria [Time frame: 30 days]
• Rate of ERCP-related perforation [Time frame: 30 days]
• Rate of ERCP-related infection [Time frame: 30 days]
• Rate of ERCP-related bleeding [Time frame: 30 days]
• The rate of total adverse events [Time frame: 30 days]
• The rate of successful pancreatic duct stent placements [Time frame: 1 day]

Eligibility criteria

Inclusion criteria

• 18-90 years old patients with native papilla who planned to undergo ERCP
• high-risk patients for post-ERCP pancreatitis must meet one or more following criteria: clinical suspicion of sphincter of Oddi dysfunction, a history of PEP, pancreatic sphincterotomy, precut sphincterotomy, difficult cannulation (>5 cannulation attempts, or >5mins cannulation time, or >1 unintentional pancreatic duct cannulation), or ballon dilatation of an intact biliary sphincter ≤ 1 min, double-wire cannulation. Additionally, patients were considered high-risk if they fulfilled two or more of the following minor criteria: female gender under 50 years old, a history of recurrent pancreatitis (two or more episodes), three or more contrast injections into the pancreatic duct with at least one injection reaching the tail of the pancreas, opacification of pancreatic acini, or brush cytology performed on the pancreatic duct.

Exclusion criteria

• Previous biliary sphincterotomy and papillary large balloon dilation
• Planned for placements of pancreatic duct stents (eg. pancreatic duct strictures, planned ampullectomy)
• Allergy to NSAIDs
• The administration of NSAIDs within 7 days
• Not suitable for NSAIDs administration (gastrointestinal hemorrhage within 4 weeks, renal dysfunction \[Cr >1.4mg/dl=120umol/l\]; presence of coagulopathy before the procedure)
• Acute pancreatitis within 7 days before ERCP or acute pancreatitis with obvious Pancreatic edema and peripancreatic fluid collections
• Hemodynamical instability
• Pregnancy or lactation
• high-risk patients with pancreatic duct wire passages

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

Triple blind

Primary purpose

Prevention

Study locations

China · 15 centers

• The first medical center, Chinese PLA General Hospital — Beijing
• Department of gastroenterology, Second Affiliated Hospital of Chongqing Medical University — Chongqing
• Department of Gastroenterology, Fujian Medical University Xiamen Humanity Hospital — Xiamen
• Harbin Medical University Affiliated Fourth Hospital — Harbin
• The Second Affiliated Hospital of Harbin Medical University — Harbin
• Department of Gastroenterology, Huaihe Hospital of Henan University — Kaifeng
• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan
• The Third Xiangya Hospital of Central South University — Changsha
• … and 7 more centers

Publications

• Dumonceau JM, Kapral C, Aabakken L, Papanikolaou IS, Tringali A, Vanbiervliet G, Beyna T, Dinis-Ribeiro M, Hritz I, Mariani A, Paspatis G, Radaelli F, Lakhtakia S, Veitch AM, van Hooft JE. ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2020 Feb;52(2):127-149. doi: 10.1055/a-1075-4080. Epub 2019 Dec 20. PMID 31863440
• Elmunzer BJ, Foster LD, Serrano J, Cote GA, Edmundowicz SA, Wani S, Shah R, Bang JY, Varadarajulu S, Singh VK, Khashab M, Kwon RS, Scheiman JM, Willingham FF, Keilin SA, Papachristou GI, Chak A, Slivka A, Mullady D, Kushnir V, Buxbaum J, Keswani R, Gardner TB, Forbes N, Rastogi A, Ross A, Law J, Yachimski P, Chen YI, Barkun A, Smith ZL, Petersen B, Wang AY, Saltzman JR, Spitzer RL, Ordiah C, Spino PMID 38219767
• Han S, Zhang J, Durkalski-Mauldin V, Foster LD, Serrano J, Cote GA, Bang JY, Varadarajulu S, Singh VK, Khashab M, Kwon RS, Scheiman JM, Willingham FF, Keilin SA, Groce JR, Lee PJ, Krishna SG, Chak A, Slivka A, Mullady D, Kushnir V, Buxbaum J, Keswani R, Gardner TB, Wani S, Edmundowicz SA, Shah RJ, Forbes N, Rastogi A, Ross A, Law J, Yachimski P, Chen YI, Barkun A, Smith ZL, Petersen BT, Wang AY, S PMID 39389431
• Akbar A, Abu Dayyeh BK, Baron TH, Wang Z, Altayar O, Murad MH. Rectal nonsteroidal anti-inflammatory drugs are superior to pancreatic duct stents in preventing pancreatitis after endoscopic retrograde cholangiopancreatography: a network meta-analysis. Clin Gastroenterol Hepatol. 2013 Jul;11(7):778-83. doi: 10.1016/j.cgh.2012.12.043. Epub 2013 Jan 30. PMID 23376320
• Halttunen J, Keranen I, Udd M, Kylanpaa L. Pancreatic sphincterotomy versus needle knife precut in difficult biliary cannulation. Surg Endosc. 2009 Apr;23(4):745-9. doi: 10.1007/s00464-008-0056-0. Epub 2008 Jul 23. PMID 18649101

Identifiers

NCT: NCT07117318 · KY20252177-F-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗