Quang Trung Tran 1,10, Pezhman Alavinejad2, Nguyen Phuong Nhu Tran 3, Omid Eslami4,5, Omar El shaarawy6, Ahmad Hormati7, Seied Saeed Seiedian1, Abazar Parsi2, Mohammed Hussien Ahmed2, Nitin Shanker Behl9, Ali Akbar Abravesh2, Shivakumar Vignesh11, Saif Salman12, Naemt Sakr 13, Tahmineh Farbod Ara2, Eskandar Hajiani2, Seyed Jalal Hashemi2

1Department of Internal Medicine, University of Medicine and Pharmacy, Hue University, Vietnam, 2Alimentary Tract Research Center, Imam Khomeini hospital clinical research development Unit, The school of medicine, Ahvaz Jundishapur University of Medical sciences, Ahvaz, Iran, 3Head of Endoscopy Department, Hue Central Hospital, Vietnam, 4Clinical Research Development Unit , Afzalipour Hospital , Kerman University of Medical Sciences, Kerman , Iran, 5Gastroenterology And Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman , Iran, 6Lecturer and consultant of Hepatology, Gastroenterology and Endoscopy, National Liver institute, Menoufia University, Egypt, 7Gastroenterology and Hepatology Disease Research Center, Qom University of Medical Sciences, Qom, Iran
8Lecturer Hepatology Gastroenterology and infectious diseases, Faculty of Medicine, Kafrelsheikh University, Cairo, Egypt, 9Institute of Gastro and Liver diseases, Fortis Hospital, Ludhiana, India, 10Department of Internal Medicine A, Greifswald University of Medicine, Greifswald, Germany, 11Division of gastroenterology, Department of Medicine, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, USA, 12Hashemite University, Faculty of Medicine, Alzarqa, Jordan, 13Assistant Lecturer and specialist of Hepatology and Gastroenterology at the National Liver Institute, Menoufia University, Egypt

Background/Aims: Post ERCP acute pancreatitis (PEAP) is the most considerable adverse event that happens up to 40% of cases in high-risk group. There are some agents such as Indomethacin, Magnesium sulfate showing the effect in preventing PEAP but the data are not homogeneous and the mechanism has not been proved. N-acetyl cysteine (NAC) is common, cheap, good tolerance medication and its efficacy in preventing PEAP has not been comprehensively established. This randomized control trial (RCT) aimed to evaluate and compare the role of suppository indomethacin and NAC in preventing PEAP.

Methods: This RCT study has been registered with number IRCT20201222049798N1. In time period of half year, patients underwent ERCP in 7 referral centers of 4 countries were randomly assigned to four groups, received either 1200 mg oral NAC (group A), 100mg rectal Indomethacin (group B), NAC plus indomethacin (group C) or water as placebo (group D) one hour before procedure. The rate and severity of any PEAP as well as related parameter were analyzed and compared.

Results: A total of 432 patients (average age 57.3 y, 58.6 % female) were recruited, included 84, 138, 115, and 95 cases in group A, B, C, and D respectively. The rate of PEAP in groups A, B, C, D were 10.7%, 17.4%, 7.8%, 20% (P(A&D), (C&D) = 0.08 & 0.01)) in sequentially. Average hospital stay duration after ERCP in groups A, B, C in comparison with D were 3.6 days, 2.6 days, 2.8 days vs. 3.7 days (P= 0.396, 0.010 & 0.012 respectively). The number needed to treat were 11 for NAC, 38 for Indomethacin and 8 if combined both of them.

Conclusion: Oral NAC played a more significant role than rectal indomethacin and the combination of both of them showed the best result that suggests a synergistic effect in preventing PEAP.

Keywords: post ERCP acute pancreatitis, N-acetyl cysteine, indomethacin, randomized control trial