W B SAUNDERS CO-ELSEVIER Acta Medica Okayama 00165085 156 6 2019 Combination of Diclofenac and Sublingual Nitrates Is Superior to Diclofenac Alone in Preventing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography 1753 1760 EN Takeshi Tomoda epartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hironari Kato Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toru Ueki Department of Internal Medicine, Fukuyama City Hospital Yutaka Akimoto Department of Gastroenterology, Iwakuni Clinical Center Hidenori Hata Department of Gastroenterology, Mitoyo General Hospital Masakuni Fujii Department of Internal Medicine, Okayama Saiseikai General Hospital Ryo Harada Department of Gastroenterology, Japanese Red Cross Okayama Hospital Tsuneyoshi Ogawa Department of Internal Medicine, Hiroshima City Hiroshima Citizens Hospital Masaki Wato Department of Gastroenterology, Kagawa Prefectural Central Hospital Masahiro Takatani Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital Minoru Matsubara Department of Internal Medicine, Sumitomo Besshi Hospital Yoshinari Kawai Department of Gastroenterology, Onomichi Municipal Hospital Hiroyuki Okada epartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences BACKGROUND & AIMS:<br/> Acute pancreatitis is a major adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Rectal administration of nonsteroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of post-ERCP pancreatitis (PEP). Little is known about the combined effects of sublingual nitrate and NSAIDs. We performed a randomized trial to assess whether the combination of NSAIDs and sublingual nitrate is more effective than NSAIDs alone in preventing PEP.<br/> METHODS:<br/> In a prospective superiority trial, eligible patients underwent ERCP at 12 endoscopic units in Japan, from March 2015 through May 2018. Patients were randomly assigned to groups given diclofenac suppositories (50 mg) within 15 minutes after the endoscopic procedure alone (diclofenac-alone group, n = 442) or in combination with sublingual isosorbide dinitrate (5 mg) 5 minutes before the endoscopic procedure (combination group, n = 444). The primary endpoint was the occurrence of PEP.<br/> RESULTS:<br/> PEP developed in 25 patients in the combination group (5.6%), and in 42 patients in the diclofenac-alone group (9.5%) (relative risk 0.59; 95% confidence interval 0.37-0.95; P = .03). Moderate to severe pancreatitis developed in 4 patients (0.9%) in the combination group, and 10 patients (2.3%) in the diclofenac-alone group (relative risk 0.12; 95% confidence interval 0.13-1.26; P = .12). There was no serious adverse event related to the additional administration of sublingual nitrate.<br/> CONCLUSIONS:<br/> In a randomized controlled trial, we found that prophylaxis with rectal diclofenac and sublingual nitrate significantly reduces the overall incidence of PEP compared with diclofenac suppository alone. ClinicalTrials.gov, no: UMIN 000016274. No potential conflict of interest relevant to this article was reported.