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

Study Overview
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Brief Summary
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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.

Official Title
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Effect of Papillary Epinephrine Spraying on Post-ERCP Pancreatitis in Patients Received Rectal Indomethacin: A Multi-center, Double-blind, Randomized Controlled Trial

Conditions
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Pancreatitis, Endoscopic Retrograde Cholangiopancreatography

Intervention / Treatment
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* Drug: Papillary epinephrine spraying
* Drug: Papillary saline spraying
* Drug: Indomethacin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PES group<br>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. | Drug: Papillary epinephrine spraying<br>* 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.<br>* Other names: PES;Drug: Indomethacin<br>* All patients without contraindications should be administrated with rectal indomethacin within 30 min before ERCP.<br>|
| Placebo Comparator: Control group<br>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. | Drug: Papillary saline spraying<br>* 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.<br>* Other names: Control;Drug: Indomethacin<br>* All patients without contraindications should be administrated with rectal indomethacin within 30 min before ERCP.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall post-ERCP pancreatitis (PEP) |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Moderate to severe PEP |  | 30 days | 
| Clinical significant gastrointestinal bleeding |  | 30 days | 
| Overall ERCP complications |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ERCP, post-ERCP pancreatitis, indomethacin, epinephrine