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

NCT03057769 | Terminated DMC

• 1 other identifier: KY20162097-1
• Study Type: interventional
• Target: 3,300
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Pancreatitis; Endoscopic Retrograde Cholangiopancreatography

Keywords

ERCP, post-ERCP pancreatitis, indomethacin, epinephrine

Outcome Measures

Primary Outcomes (1)

• Overall post-ERCP pancreatitis (PEP)

  30 days

Secondary Outcomes (3)

• Moderate to severe PEP

  30 days

• Clinical significant gastrointestinal bleeding

  30 days

• Overall ERCP complications

  30 days

Other Outcomes (5)

• Severity of PEP evaluated by updated Atlanta criteria

  30 days

• ERCP-related perforation

  30 days

• Biliary infection

  30 days

Study Arms (2)

PES group

EXPERIMENTAL

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; Drug: Indomethacin

Control group

PLACEBO COMPARATOR

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; Drug: Indomethacin

Interventions

Papillary epinephrine spraying DRUG

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.

Also known as: PES

PES group

Papillary saline spraying DRUG

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.

Also known as: Control

Control group

Indomethacin DRUG

All patients without contraindications should be administrated with rectal indomethacin within 30 min before ERCP.

Control group; PES group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old patients planned for ERCP.

You may not qualify if:

• 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

Sponsors & Collaborators

• Air Force Military Medical University, China: lead

Study Sites (10)

Department of Gastroenterology, Successful Hospital of Xiamen university

Xiamen, Fujian, 361000, China

Location

Department of Gastroenterology, Zhongshan Hospital of Xiamen university

Xiamen, Fujian, 361004, China

Location

Department of General Surgery, The First Hospital of Lanzhou University

Lanzhou, Gansu, 730000, China

Location

Endoscopy Center, Ankang Central Hospital

Ankang, Shaanxi, 725000, China

Location

Xijing Hospital of Digestive Diseases

Xi'an, Shaanxi, 710032, China

Location

Department of Gastroenterology, No. 451 Hospital

Xi'an, Shaanxi, 710068, China

Location

Department of Gastroenterology, The First Affiliated Hospital of the Medical College, Shihezi University

Shihezi, Xinjiang, 832008, China

Location

Department of Gastroenterology, Urumqi General Hospital of Lanzhou Military Region

Ürümqi, Xinjiang, 830000, China

Location

Department of Gastroenterology, Hangzhou First People's Hospital

Hangzhou, Zhejiang, 310006, China

Location

Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University

Yinchuan, 750004, China

Location

Related Publications (14)

• Freeman ML, Guda NM. Prevention of post-ERCP pancreatitis: a comprehensive review. Gastrointest Endosc. 2004 Jun;59(7):845-64. doi: 10.1016/s0016-5107(04)00353-0. No abstract available.

  PMID: 15173799 BACKGROUND

• 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.

  PMID: 25148137 BACKGROUND

• 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.

  PMID: 25973947 BACKGROUND

• 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.

  PMID: 27133971 BACKGROUND

• 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.

  PMID: 23164513 BACKGROUND

• 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.

  PMID: 19159075 BACKGROUND

• 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. doi: 10.1055/s-2007-1004185.

  PMID: 9255527 BACKGROUND

• 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. doi: 10.1016/s0016-5107(97)70089-0.

  PMID: 9378207 BACKGROUND

• 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. doi: 10.1007/BF02367779.

  PMID: 8574325 BACKGROUND

• 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.

  PMID: 21392105 BACKGROUND

• 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 Jul;48(7):657-83. doi: 10.1055/s-0042-108641. Epub 2016 Jun 14.

  PMID: 27299638 BACKGROUND

• 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.

  PMID: 23896955 BACKGROUND

• 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.

  PMID: 24054878 BACKGROUND

• Luo H, Wang X, Zhang R, Liang S, Kang X, Zhang X, Lou Q, Xiong K, Yang J, Si L, Liu W, Liu Y, Zhou Y, Wang S, Yang M, Chen W, Han Y, Shang G, Yang X, He Y, Zou Q, Guo W, Dai Y, Zeng W, Zhu X, Gong R, Li X, Nie Z, Wang Q, Wang L, Pan Y, Guo X, Fan D. Rectal Indomethacin and Spraying of Duodenal Papilla With Epinephrine Increases Risk of Pancreatitis Following Endoscopic Retrograde Cholangiopancreatography. Clin Gastroenterol Hepatol. 2019 Jul;17(8):1597-1606.e5. doi: 10.1016/j.cgh.2018.10.043. Epub 2018 Oct 31.

  PMID: 30391434 DERIVED

MeSH Terms

Conditions

Pancreatitis

Interventions

Indomethacin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: February 15, 2017
• First Posted: February 20, 2017
• Study Start: February 1, 2017
• Primary Completion: October 26, 2017
• Study Completion: October 26, 2017
• Last Updated: October 27, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (10)