Effect of Papillary Epinephrine Spraying on Post-ERCP Pancreatitis in Patients Received Rectal Indomethacin

Air Force Military Medical University of People's Liberation Army

Status: Terminated

Conditions: Pancreatitis; Endoscopic Retrograde Cholangiopancreatography

Treatments: Drug: Papillary saline spraying; Drug: Papillary epinephrine spraying; Drug: Indomethacin

Study type: Interventional

Funder types: Other

Identifiers

NCT03057769

KY20162097-1

Details and patient eligibility

About

Acute pancreatitis is the most common and feared complication of ERCP, occurring after 1% to 30% of procedures. It accounts for substantial morbidity and represents a substantial cost to health-care systems. European Society of Gastrointestinal Endoscopy and Japanese Society of Hepato-Biliary-Pancreatic surgery guidelines and recently large-scale RCT recommended routine use of NSAIDs indomethacin rectally before ERCP. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to inhibit prostaglandin synthesis, phospholipase A2 activity, and neutrophil/endothelial cell attachment, which is believed to play a key role in the pathogenesis of acute pancreatitis.

Other possible mechanisms have been suggested in the occurrence of pancreatitis. Papillary edema caused by manipulations during cannulation or endoscopic treatment has received the most attention. The papillary edema may cause temporary outflow obstruction of pancreatic juice, and then increase ductal pressure, resulting in the occurrence of pancreatitis. Topical application of epinephrine on the papilla may reduce papillary edema by decreasing capillary permeability or by relaxing the sphincter of Oddi. A meta-analysis (including 2 existing RCTs and post-hoc analysis of our previous study) of papillary epinephrine spraying compared with saline spraying or no intervention indicates a potential relative risk reduction of PEP (RR 0.34, 95%CI 0.19-0.61). Papillary epinephrine spraying may be an inexpensive and convenient alternative for prevention of post-ERCP pancreatitis. A large pragmatic RCT to determine whether routine using papillary epinephrine spraying can reduce post-ERCP pancreatitis is needed.

Enrollment: 3,300 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 18-80 years old patients planned for ERCP.

Exclusion criteria

• contraindications to ERCP
• allergy to epinephrine or NSAIDs
• Not suitable for pre-ERCP indomethacin (received NSAIDs within 7 days before the procedure; gastrointestinal hemorrhage within 4 weeks; renal dysfunction [Cr >1.4mg/dl=120umol/l]; presence of coagulopathy before the procedure)
• previous biliary sphincterotomy without planned pancreatic duct manipulation
• ERCP for biliary stent removal or exchange without planned pancreatic duct manipulation
• acute pancreatitis within 3 days before the procedure
• unwilling or inability to provide consent
• pregnant or breastfeeding women

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

3,300 participants in 2 patient groups, including a placebo group

PES group

Experimental group

Description:

All patients in this group receive 20 ml of 0.02% epinephrine sprayed on the duodenal papilla, over a period of 10-15 seconds using sphincterotome, at the end of procedure, just before the withdrawal of endoscope.

Treatment:

Drug: Indomethacin

Drug: Papillary epinephrine spraying

Control group

Placebo Comparator group

Description:

All patients in this group receive 20 ml of saline sprayed on the duodenal papilla, over a period of 10-15 seconds using sphincterotome, at the end of procedure, just before the withdrawal of endoscope.

Treatment:

Drug: Indomethacin

Drug: Papillary saline spraying