Duke University School of Medicine. Durham, VA, USA

Pilot Study of Aprepitant for Prevention of Post-ERCP Pancreatitis in High Risk Patients: A Phase II Randomized, Double-Blind Placebo Controlled Trial

Tilak Upendra Shah, Rodger Liddle, M Stanley Branch, Paul Jowell, Jorge Obando, Martin Poleski

Abstract


Objectives Animal studies have demonstrated a role for substance P binding to neurokinin-1 receptor in the pathogenesis of acute pancreatitis. Our aim was to assess the efficacy of a neurokinin-1 receptor antagonist (aprepitant) at preventing post-ERCP pancreatitis in high risk patients. Design Randomized, double-blind, placebo controlled trial at a single academic medical center. Intervention Patients at high risk for post-ERCP pancreatitis received either placebo or oral aprepitant administered 4 hours prior to ERCP, 80 mg 24 hours after the first dose, and then 80 mg 24 hours after the second dose. Patients Thirty-four patients received aprepitant and 39 patients received placebo. Statistics Fisher’s exact test was used to compare incidence of post-ERCP pancreatitis in the two groups. Results Baseline characteristics were similar between the two groups. Incidence of acute pancreatitis was 7 in the aprepitant group and 7 in the placebo group. Hospitalization within 7 days post-procedure for abdominal pain that did not meet criteria for acute pancreatitis occurred in 6 and 9 patients in the aprepitant and placebo groups respectively (P=0.772). Conclusions Aprepitant did not lower incidence of post-ERCP pancreatitis in this preliminary human study. Larger studies potentially using the recently available intravenous formulation are necessary to conclusively clarify the efficacy of aprepitant in this setting.

Image: Duke University  School of Medicine. Durham, VA, USA.


Keywords


aprepitant; Cholangiopancreatography, Endoscopic Retrograde; Pancreatitis; Receptors, Neurokinin-1

Full Text:

HTML PDF

References


Mallery, J.S., et al., Complications of ERCP. Gastrointest Endosc, 2003. 57(6): p. 633-8.

Freeman, M.L., et al., Complications of endoscopic biliary sphincterotomy. N Engl J Med, 1996. 335(13): p. 909-18.

Loperfido, S., et al., Major early complications from diagnostic and therapeutic ERCP: a prospective multicenter study. Gastrointest Endosc, 1998. 48(1): p. 1-10.

Andriulli, A., et al., Incidence rates of post-ERCP complications: a systematic survey of prospective studies. Am J Gastroenterol, 2007. 102(8): p. 1781-8.

Akashi, R., et al., Mechanism of pancreatitis caused by ERCP. Gastrointest Endosc, 2002. 55(1): p. 50-4.

Cheon, Y.K., et al., Frequency and severity of post-ERCP pancreatitis correlated with extent of pancreatic ductal opacification. Gastrointest Endosc, 2007. 65(3): p. 385-93.

Pezzilli, R., et al., Mechanisms involved in the onset of post-ERCP pancreatitis. JOP, 2002. 3(6): p. 162-8.

Raty, S., et al., Post-ERCP pancreatitis: reduction by routine antibiotics. J Gastrointest Surg, 2001. 5(4): p. 339-45; discussion 345.

Mazaki, T., H. Masuda, and T. Takayama, Prophylactic pancreatic stent placement and post-ERCP pancreatitis: a systematic review and meta-analysis. Endoscopy, 2010. 42(10): p. 842-53.

Singh, P., et al., Does prophylactic pancreatic stent placement reduce the risk of post-ERCP acute pancreatitis? A meta-analysis of controlled trials. Gastrointest Endosc, 2004. 60(4): p. 544-50.

Sofuni, A., et al., Prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis by an endoscopic pancreatic spontaneous dislodgement stent. Clin Gastroenterol Hepatol, 2007. 5(11): p. 1339-46.

Zheng, M., et al., Meta-analysis of prophylactic allopurinol use in post-endoscopic retrograde cholangiopancreatography pancreatitis. Pancreas, 2008. 37(3): p. 247-53.

Rabenstein, T., et al., Low-molecular-weight heparin does not prevent acute post-ERCP pancreatitis. Gastrointest Endosc, 2004. 59(6): p. 606-13.

Kapetanos, D., et al., A randomized controlled trial of pentoxifylline for the prevention of post-ERCP pancreatitis. Gastrointest Endosc, 2007. 66(3): p. 513-8.

Bang, U.C., et al., Meta-analysis: Nitroglycerin for prevention of post-ERCP pancreatitis. Aliment Pharmacol Ther, 2009. 29(10): p. 1078-85.

Chen, B., T. Fan, and C.H. Wang, A meta-analysis for the effect of prophylactic GTN on the incidence of post-ERCP pancreatitis and on the successful rate of cannulation of bile ducts. BMC Gastroenterol, 2010. 10: p. 85.

Elmunzer, B.J., et al., A meta-analysis of rectal NSAIDs in the prevention of post-ERCP pancreatitis. Gut, 2008. 57(9): p. 1262-7.

Dai, H.F., X.W. Wang, and K. Zhao, Role of nonsteroidal anti-inflammatory drugs in the prevention of post-ERCP pancreatitis: a meta-analysis. Hepatobiliary Pancreat Dis Int, 2009. 8(1): p. 11-6.

Tsujino, T., T. Kawabe, and M. Omata, Antiproteases in preventing post-ERCP acute pancreatitis. JOP, 2007. 8(4 Suppl): p. 509-17.

Jowell, P.S., et al., Intravenous synthetic secretin reduces the incidence of pancreatitis induced by endoscopic retrograde cholangiopancreatography. Pancreas, 2011. 40(4): p. 533-9.

Andriulli, A., et al., Prophylactic administration of somatostatin or gabexate does not prevent pancreatitis after ERCP: an updated meta-analysis. Gastrointest Endosc, 2007. 65(4): p. 624-32.

Nathan, J.D., et al., Capsaicin vanilloid receptor-1 mediates substance P release in experimental pancreatitis. Am J Physiol Gastrointest Liver Physiol, 2001. 281(5): p. G1322-8.

Nathan, J.D., et al., Primary sensory neurons: a common final pathway for inflammation in experimental pancreatitis in rats. Am J Physiol Gastrointest Liver Physiol, 2002. 283(4): p. G938-46.

Bhatia, M., et al., Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury. Proc Natl Acad Sci U S A, 1998. 95(8): p. 4760-5.

Baluk, P., et al., NK1 receptors mediate leukocyte adhesion in neurogenic inflammation in the rat trachea. Am J Physiol, 1995. 268(2 Pt 1): p. L263-9.

He, Z.J., et al., Intraductal administration of an NK1 receptor antagonist attenuates the inflammatory response to retrograde infusion of radiological contrast in rats: implications for the pathogenesis and prevention of ERCP-induced pancreatitis. Pancreas, 2003. 27(1): p. e13-7.

Jin, Y., et al., Efficacy and safety of aprepitant in the prevention of chemotherapy-induced nausea and vomiting: a pooled analysis. Support Care Cancer, 2011.

Basch, E., et al., Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol, 2011.

Hargreaves, R., et al., Development of aprepitant, the first neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Ann N Y Acad Sci, 2011. 1222: p. 40-8.

Cotton, P.B., et al., Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc, 1991. 37(3): p. 383-93.

Liddle, R.A. and J.D. Nathan, Neurogenic inflammation and pancreatitis. Pancreatology, 2004. 4(6): p. 551-9; discussion 559-60.

Noble, M.D., et al., A pH-sensitive, neurogenic pathway mediates disease severity in a model of post-ERCP pancreatitis. Gut, 2008. 57(11): p. 1566-71.

Shrikhande, S.V., et al., NK-1 receptor gene expression is related to pain in chronic pancreatitis. Pain, 2001. 91(3): p. 209-17.




DOI: http://dx.doi.org/10.6092/1590-8577/855

NBN: http://nbn.depositolegale.it/urn%3Anbn%3Ait%3Aunina-16319

Article Metrics

Metrics Loading ...

Metrics powered by PLOS ALM

Refbacks

  • There are currently no refbacks.




Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

ISSN 1590-8577 | JOP is published by CAB - Center for Libraries at "Federico II" University of Naples using Open Journal System