Randomized Controlled Trial
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2016; 22(21): 5114-5121
Published online Jun 7, 2016. doi: 10.3748/wjg.v22.i21.5114
Suppository naproxen reduces incidence and severity of post-endoscopic retrograde cholangiopancreatography pancreatitis: Randomized controlled trial
Fariborz Mansour-Ghanaei, Farahnaz Joukar, Zahra Taherzadeh, Homayoon Sokhanvar, Tolou Hasandokht
Fariborz Mansour-Ghanaei, Farahnaz Joukar, Zahra Taherzadeh, Homayoon Sokhanvar, Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Razi Hospital, Rasht 41448-95655, Iran
Tolou Hasandokht, Department of Community Medicine, Guilan University of Medical Sciences, Rasht 41448-95655, Iran
Author contributions: Mansour-Ghanaei F and Joukar F designed the study; Mansour-Ghanaei F, Taherzadeh Z and Sokhanvar H collected data; Joukar F contributed to data analysis; Joukar F and Sokhanvar H supervised the procedure; Mansour-Ghanaei F, Joukar F and Hasandokht T drafted the manuscript; all authors read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the ethics committee of the Gastrointestinal and Liver Diseases Research Center of Guilan University of Medical Science.
Clinical trial registration statement: This study is registered at Iranian Registry of Clinical Trials. The registration identification number is IRCT201105301155N14.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: None declared.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Fariborz Mansour-Ghanaei, MD, AGAF, Professor of Gastroenterology, Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Razi Hospital, Sardar-Jangle Ave., P.O., Rasht 41448-95655, Iran. ghanaei@gums.ac.ir
Telephone: +98-13-33535116 Fax: +98-13-33534951
Received: June 25, 2015
Peer-review started: June 27, 2015
First decision: October 15, 2015
Revised: October 27, 2015
Accepted: January 17, 2016
Article in press: January 18, 2016
Published online: June 7, 2016
Processing time: 340 Days and 4 Hours
Abstract

AIM: To determine the efficacy of rectally administered naproxen for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP).

METHODS: This double-blind randomized control trial conducted from January 2013 to April 2014 at the Gastrointestinal and Liver Diseases Research Center in Rasht, Iran. A total of 324 patients were selected from candidates for diagnostic or therapeutic ERCP by using the simple sampling method. Patients received a single dose of Naproxen (500 mg; n = 162) or a placebo (n = 162) per rectum immediately before ERCP. The overall incidence of PEP, incidence of mild to severe PEP, serum amylase levels and adverse effects were measured. The primary outcome measure was the development of pancreatitis onset of pain in the upper abdomen and elevation of the serum amylase level to > 3 × the upper normal limit (60-100 IU/L) within 24 h after ERCP. The severity of PEP was classified according to the duration of therapeutic intervention for PEP: mild, 2-3 d; moderate 4-10 d; and severe, > 10 d and/or necessitated surgical or intensive treatment, or contributed to death.

RESULTS: PEP occurred in 12% (40/324) of participants, and was significantly more frequent in the placebo group compared to the naproxen group (P < 0.01). Of the participants, 25.9% (84/324) developed hyperamylasemia within 2 h of procedure completion, among whom only 35 cases belonged to the naproxen group (P < 0.01). The incidence of PEP was significantly higher in female sex, in patients receiving pancreatic duct injection, more than 3 times pancreatic duct cannulations, and ERCP duration more than 40 min (Ps < 0.01). There were no statistically significant differences between the groups regarding the procedures or factors that might increase the risk of PEP, sphincterotomy, precut requirement, biliary duct injection and number of pancreatic duct cannulations. In the subgroup of patients with pancreatic duct injection, the rate of pancreatitis in the naproxen group was significantly lower than that in the placebo (6 patients vs 23 patients, P < 0.01, RRR = 12%, AR = 0.3, 95%CI: 0.2-0.6). Naproxen reduced the PEP in patients with ≥ 3 pancreatic cannulations (P < 0.01, RRR = 25%, AR = 0.1, 95%CI: 0.1-0.4) and an ERCP duration > 40 min (P < 0.01, RRR = 20%, AR = 0.9, 95%CI: 0.4-1.2).

CONCLUSION: Single dose of suppository naproxen administered immediately before ERCP reduces the incidence of PEP.

Keywords: Naproxen; Nonsteroidal anti-inflammatory drugs; Pancreatic duct injection; Post-endoscopic retrograde cholangiopancreatography; Pancreatitis; Serum amylase

Core tip: Acute pancreatitis is the most common serious complication of endoscopic retrograde cholangiopancreatography (ERCP); prevention of post-ERCP pancreatitis (PEP) has become more challenging. The use of nonsteroidal anti-inflammatory drugs is effective in this condition. This study evaluated the efficacy of rectally administered naproxen for the prevention of PEP in composition with placebo immediately before ERCP.