Rectal Indomethacin and Oral Tacrolimus Versus Combination to Prevent Post-ERCP Pancreatitis

Summary

This research is being done to see if using oral tacrolimus before endoscopy, can prevent pancreatitis that may occur after ERCP (a type of gastrointestinal endoscopy).

Timeline

Start

2023-01-18

Primary completion

2026-12

Completion

2026-12

Publications

• Background Coelho-Prabhu N, Shah ND, Van Houten H, Kamath PS, Baron TH. Endoscopic retrograde cholangiopancreatography: utilisation and outcomes in a 10-year population-based cohort. BMJ Open. 2013 May 31;3(5):e002689. doi: 10.1136/bmjopen-2013-002689.
• Background Mazen Jamal M, Yoon EJ, Saadi A, Sy TY, Hashemzadeh M. Trends in the utilization of endoscopic retrograde cholangiopancreatography (ERCP) in the United States. Am J Gastroenterol. 2007 May;102(5):966-75. doi: 10.1111/j.1572-0241.2007.01127.x. Epub 2007 Mar 23.
• Background Moffatt DC, Yu BN, Yie W, Bernstein CN. Trends in utilization of diagnostic and therapeutic ERCP and cholecystectomy over the past 25 years: a population-based study. Gastrointest Endosc. 2014 Apr;79(4):615-22. doi: 10.1016/j.gie.2013.08.028. Epub 2013 Oct 8.
• Background Testoni PA, Mariani A, Giussani A, Vailati C, Masci E, Macarri G, Ghezzo L, Familiari L, Giardullo N, Mutignani M, Lombardi G, Talamini G, Spadaccini A, Briglia R, Piazzi L; SEIFRED Group. Risk factors for post-ERCP pancreatitis in high- and low-volume centers and among expert and non-expert operators: a prospective multicenter study. Am J Gastroenterol. 2010 Aug;105(8):1753-61. doi: 10.1038/ajg.2010.136. Epub 2010 Apr 6.
• Background Fan JH, Qian JB, Wang YM, Shi RH, Zhao CJ. Updated meta-analysis of pancreatic stent placement in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis. World J Gastroenterol. 2015 Jun 28;21(24):7577-83. doi: 10.3748/wjg.v21.i24.7577.
• Background Lyu Y, Cheng Y, Wang B, Xu Y, Du W. What is impact of nonsteroidal anti-inflammatory drugs in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis of randomized controlled trials. BMC Gastroenterol. 2018 Jul 4;18(1):106. doi: 10.1186/s12876-018-0837-4.
• Background Levenick JM, Gordon SR, Fadden LL, Levy LC, Rockacy MJ, Hyder SM, Lacy BE, Bensen SP, Parr DD, Gardner TB. Rectal Indomethacin Does Not Prevent Post-ERCP Pancreatitis in Consecutive Patients. Gastroenterology. 2016 Apr;150(4):911-7; quiz e19. doi: 10.1053/j.gastro.2015.12.040. Epub 2016 Jan 9.
• Background Shibasaki F, Hallin U, Uchino H. Calcineurin as a multifunctional regulator. J Biochem. 2002 Jan;131(1):1-15. doi: 10.1093/oxfordjournals.jbchem.a003063.
• Background Rusnak F, Mertz P. Calcineurin: form and function. Physiol Rev. 2000 Oct;80(4):1483-521. doi: 10.1152/physrev.2000.80.4.1483.
• Background Aramburu J, Rao A, Klee CB. Calcineurin: from structure to function. Curr Top Cell Regul. 2000;36:237-95. doi: 10.1016/s0070-2137(01)80011-x. No abstract available.
• Background Muili KA, Ahmad M, Orabi AI, Mahmood SM, Shah AU, Molkentin JD, Husain SZ. Pharmacological and genetic inhibition of calcineurin protects against carbachol-induced pathological zymogen activation and acinar cell injury. Am J Physiol Gastrointest Liver Physiol. 2012 Apr 15;302(8):G898-905. doi: 10.1152/ajpgi.00545.2011. Epub 2012 Feb 9.
• Background Thiruvengadam NR, Forde KA, Chandrasekhara V, Ahmad NA, Ginsberg GG, Khungar V, Kochman ML. Tacrolimus and Indomethacin Are Safe and Effective at Reducing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography in Patients Who Have Undergone Liver Transplantation. Clin Gastroenterol Hepatol. 2020 May;18(5):1224-1232.e1. doi: 10.1016/j.cgh.2019.10.014. Epub 2019 Oct 14.
• Background Venkataramanan R, Swaminathan A, Prasad T, Jain A, Zuckerman S, Warty V, McMichael J, Lever J, Burckart G, Starzl T. Clinical pharmacokinetics of tacrolimus. Clin Pharmacokinet. 1995 Dec;29(6):404-30. doi: 10.2165/00003088-199529060-00003.
• Background Wen L, Javed TA, Yimlamai D, Mukherjee A, Xiao X, Husain SZ. Transient High Pressure in Pancreatic Ducts Promotes Inflammation and Alters Tight Junctions via Calcineurin Signaling in Mice. Gastroenterology. 2018 Oct;155(4):1250-1263.e5. doi: 10.1053/j.gastro.2018.06.036. Epub 2018 Jun 19.
• Background Orabi AI, Wen L, Javed TA, Le T, Guo P, Sanker S, Ricks D, Boggs K, Eisses JF, Castro C, Xiao X, Prasadan K, Esni F, Gittes GK, Husain SZ. Targeted inhibition of pancreatic acinar cell calcineurin is a novel strategy to prevent post-ERCP pancreatitis. Cell Mol Gastroenterol Hepatol. 2017 Jan;3(1):119-128. doi: 10.1016/j.jcmgh.2016.08.006.
• Akshintala VS, Husain SZ, Brenner TA, Singh A, Singh VK, Khashab MA, Sperna Weiland CJ, van Geenen EJM, Bush N, Barakat M, Srivastava A, Kochhar R, Talukdar R, Rodge G, Wu CCH, Lakhtakia S, Sinha SK, Goenka MK, Reddy DN. Rectal INdomethacin, oral TacROlimus, or their combination for the prevention of post-ERCP pancreatitis (INTRO Trial): Protocol for a randomized, controlled, double-blinded trial. Pancreatology. 2022 Nov;22(7):887-893. doi: 10.1016/j.pan.2022.07.008. Epub 2022 Jul 19.

Drugs

Indications