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

Pancreatitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03057769
• Other study ID #: KY20162097-1
• Status: Terminated
• Phase: N/A
• First received: February 15, 2017
• Last updated: October 25, 2017
• Start date: February 1, 2017
• Est. completion date: October 26, 2017

Study information

• Verified date: October 2017
• Source: Fourth Military Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3300
• Est. completion date: October 26, 2017
• Est. primary completion date: October 26, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Endoscopic Retrograde Cholangiopancreatography
• Pancreatitis

Intervention

Drug:
• Papillary epinephrine spraying
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.
• Papillary saline spraying
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.
• Indomethacin
All patients without contraindications should be administrated with rectal indomethacin within 30 min before ERCP.

Locations

Country	Name	City	State
China	Endoscopy Center, Ankang Central Hospital	Ankang	Shaanxi
China	Department of Gastroenterology, Hangzhou First People's Hospital	Hangzhou	Zhejiang
China	Department of General Surgery, The First Hospital of Lanzhou University	Lanzhou	Gansu
China	Department of Gastroenterology, The First Affiliated Hospital of the Medical College, Shihezi University	Shihezi	Xinjiang
China	Department of Gastroenterology, Urumqi General Hospital of Lanzhou Military Region	Urumqi	Xinjiang
China	Department of Gastroenterology, No. 451 Hospital	Xi'an	Shaanxi
China	Xijing Hospital of Digestive Diseases	Xi'an	Shaanxi
China	Department of Gastroenterology, Successful Hospital of Xiamen university	Xiamen	Fujian
China	Department of Gastroenterology, Zhongshan Hospital of Xiamen university	Xiamen	Fujian
China	Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University	Yinchuan

Sponsors (1)

Lead Sponsor	Collaborator
Fourth Military Medical University

Country where clinical trial is conducted

China, 

References & Publications (13)

Ding X, Chen M, Huang S, Zhang S, Zou X. Nonsteroidal anti-inflammatory drugs for prevention of post-ERCP pancreatitis: a meta-analysis. Gastrointest Endosc. 2012 Dec;76(6):1152-9. doi: 10.1016/j.gie.2012.08.021. — View Citation

Dumonceau JM, Andriulli A, Elmunzer BJ, Mariani A, Meister T, Deviere J, Marek T, Baron TH, Hassan C, Testoni PA, Kapral C; European Society of Gastrointestinal Endoscopy. Prophylaxis of post-ERCP pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - updated June 2014. Endoscopy. 2014 Sep;46(9):799-815. doi: 10.1055/s-0034-1377875. Epub 2014 Aug 22. — View Citation

Freeman ML, Guda NM. Prevention of post-ERCP pancreatitis: a comprehensive review. Gastrointest Endosc. 2004 Jun;59(7):845-64. Review. — View Citation

Johnson GK, Geenen JE, Johanson JF, Sherman S, Hogan WJ, Cass O. Evaluation of post-ERCP pancreatitis: potential causes noted during controlled study of differing contrast media. Midwest Pancreaticobiliary Study Group. Gastrointest Endosc. 1997 Sep;46(3):217-22. — View Citation

Luo H, Zhao L, Leung J, Zhang R, Liu Z, Wang X, Wang B, Nie Z, Lei T, Li X, Zhou W, Zhang L, Wang Q, Li M, Zhou Y, Liu Q, Sun H, Wang Z, Liang S, Guo X, Tao Q, Wu K, Pan Y, Guo X, Fan D. Routine pre-procedural rectal indometacin versus selective post-procedural rectal indometacin to prevent pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography: a multicentre, single-blinded, randomised controlled trial. Lancet. 2016 Jun 4;387(10035):2293-2301. doi: 10.1016/S0140-6736(16)30310-5. Epub 2016 Apr 28. — View Citation

Matsushita M, Takakuwa H, Shimeno N, Uchida K, Nishio A, Okazaki K. Epinephrine sprayed on the papilla for prevention of post-ERCP pancreatitis. J Gastroenterol. 2009;44(1):71-5. doi: 10.1007/s00535-008-2272-8. Epub 2009 Jan 22. — View Citation

Ohno T, Katori M, Nishiyama K, Saigenji K. Direct observation of microcirculation of the basal region of rat gastric mucosa. J Gastroenterol. 1995 Oct;30(5):557-64. — View Citation

Tarnasky P, Cunningham J, Cotton P, Hoffman B, Palesch Y, Freeman J, Curry N, Hawes R. Pancreatic sphincter hypertension increases the risk of post-ERCP pancreatitis. Endoscopy. 1997 May;29(4):252-7. — View Citation

Tenner S, Baillie J, DeWitt J, Vege SS; American College of Gastroenterology. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013 Sep;108(9):1400-15; 1416. doi: 10.1038/ajg.2013.218. Epub 2013 Jul 30. Erratum in: Am J Gastroenterol. 2014 Feb;109(2):302. — View Citation

Testoni PA, Mariani A, Aabakken L, Arvanitakis M, Bories E, Costamagna G, Devière 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 Jul;48(7):657-83. doi: 10.1055/s-0042-108641. Epub 2016 Jun 14. — View Citation

Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013 Jul-Aug;13(4 Suppl 2):e1-15. doi: 10.1016/j.pan.2013.07.063. — View Citation

Xu LH, Qian JB, Gu LG, Qiu JW, Ge ZM, Lu F, Wang YM, Li YM, Lu HS. Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis by epinephrine sprayed on the papilla. J Gastroenterol Hepatol. 2011 Jul;26(7):1139-44. doi: 10.1111/j.1440-1746.2011.06718.x. — View Citation

Yokoe M, Takada T, Mayumi T, Yoshida M, Isaji S, Wada K, Itoi T, Sata N, Gabata T, Igarashi H, Kataoka K, Hirota M, Kadoya M, Kitamura N, Kimura Y, Kiriyama S, Shirai K, Hattori T, Takeda K, Takeyama Y, Hirota M, Sekimoto M, Shikata S, Arata S, Hirata K. Japanese guidelines for the management of acute pancreatitis: Japanese Guidelines 2015. J Hepatobiliary Pancreat Sci. 2015 Jun;22(6):405-32. doi: 10.1002/jhbp.259. Epub 2015 May 13. Review. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Severity of PEP evaluated by updated Atlanta criteria		30 days
Other	ERCP-related perforation		30 days
Other	Biliary infection		30 days
Other	Length of post-procedure hospital stay		30 days
Other	Death		30 days
Primary	Overall post-ERCP pancreatitis (PEP)		30 days
Secondary	Moderate to severe PEP		30 days
Secondary	Clinical significant gastrointestinal bleeding		30 days
Secondary	Overall ERCP complications		30 days