Gastroenterology

Gastroenterology

Volume 156, Issue 6, May 2019, Pages 1753-1760.e1
Gastroenterology

Original Research
Full Report: Clinical—Pancreas
Combination of Diclofenac and Sublingual Nitrates Is Superior to Diclofenac Alone in Preventing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography

https://doi.org/10.1053/j.gastro.2019.01.267Get rights and content

Background & Aims

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.

Methods

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.

Results

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.

Conclusions

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

Section snippets

Study Design

The study was a 2-arm, multicenter, prospective, randomized, superiority unblinded trial to evaluate the combined effect of nitrate and diclofenac in the prevention of PEP, in comparison with the efficacy of diclofenac alone. The study was conducted between March 2015 and May 2018 at 12 centers in Japan; more than 200 ERCPs per year were performed in each center. A total of 900 eligible patients were randomly assigned to receive a 50-mg diclofenac suppository either alone or in combination with

Patients

Between March 2015 and May 2018, 10,188 patients were scheduled to undergo ERCP and assessed for eligibility across 12 centers. After screening, 9288 patients met the exclusion criteria and 44 declined to participate. Patients were deemed to be inappropriate for trial when their health was unstable due severe cholangitis (n = 55), advanced cancer (n = 26), severe comorbidity (n = 15), decompensated cirrhosis (n = 11), or advanced age (> 85 years) (n = 36). The remaining 900 patients were

Discussion

Rectal administration of NSAIDs has been widely used for the prevention of PEP, and has been recommended to be administered in all patients without contraindications in the European Society of Gastrointestinal Endoscopy and Japanese Society of Hepato-Biliary-Pancreatic Surgery guidelines.11, 12

In this multicenter, randomized controlled trial, we found that the combination therapy with diclofenac and sublingual nitrate significantly reduced the incidence of PEP as compared with that with the use

Acknowledgments

The authors thank the staff of the Department of Clinical Data Management, Center for Innovative Clinical Medicine of Okayama University Hospital for their assistance in relation to the case registration system.

We also thank Koichiro Tsutsumi, Shigeru Horiguchi, Kazuyuki Matsumoto, Daisuke Uchida, Shinichiro Muro, Saimon Takata, Shuntaro Yabe, Sho Mizukawa, and Yousuke Saragai of Okayama University Hospital for their help in accomplishing this study.

Author contributions: TT and HK took part in

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    Conflicts of interest The authors disclose no conflicts.

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