Combination of Diclofenac and Sublingual Nitrates Is Superior to Diclofenac Alone in Preventing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography

Takeshi Tomoda, Hironari Katou, Toru Ueki, Yutaka Akimoto, Hidenori Hata, Masakuni Fujii, Ryo Harada, Tsuneyoshi Ogawa, Masaki Wato, Masahiro Takatani, Minoru Matsubara, Yoshinari Kawai, Hiroyuki Okada

Research output: Contribution to journalArticle

Abstract

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

Original languageEnglish
Pages (from-to)1753-1760.e1
JournalGastroenterology
Volume156
Issue number6
DOIs
Publication statusPublished - May 1 2019

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Diclofenac
Endoscopic Retrograde Cholangiopancreatography
Pancreatitis
Nitrates
Anti-Inflammatory Agents
Suppositories
Pharmaceutical Preparations
Sublingual Administration
Confidence Intervals
Rectal Administration
Isosorbide Dinitrate
Incidence
Japan
Randomized Controlled Trials

Keywords

  • Drug
  • Inflammation
  • Pancreas
  • Smooth-Muscle Relaxant

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Combination of Diclofenac and Sublingual Nitrates Is Superior to Diclofenac Alone in Preventing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography. / Tomoda, Takeshi; Katou, Hironari; Ueki, Toru; Akimoto, Yutaka; Hata, Hidenori; Fujii, Masakuni; Harada, Ryo; Ogawa, Tsuneyoshi; Wato, Masaki; Takatani, Masahiro; Matsubara, Minoru; Kawai, Yoshinari; Okada, Hiroyuki.

In: Gastroenterology, Vol. 156, No. 6, 01.05.2019, p. 1753-1760.e1.

Research output: Contribution to journalArticle

Tomoda, Takeshi ; Katou, Hironari ; Ueki, Toru ; Akimoto, Yutaka ; Hata, Hidenori ; Fujii, Masakuni ; Harada, Ryo ; Ogawa, Tsuneyoshi ; Wato, Masaki ; Takatani, Masahiro ; Matsubara, Minoru ; Kawai, Yoshinari ; Okada, Hiroyuki. / Combination of Diclofenac and Sublingual Nitrates Is Superior to Diclofenac Alone in Preventing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography. In: Gastroenterology. 2019 ; Vol. 156, No. 6. pp. 1753-1760.e1.
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abstract = "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",
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T1 - Combination of Diclofenac and Sublingual Nitrates Is Superior to Diclofenac Alone in Preventing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography

AU - Tomoda, Takeshi

AU - Katou, Hironari

AU - Ueki, Toru

AU - Akimoto, Yutaka

AU - Hata, Hidenori

AU - Fujii, Masakuni

AU - Harada, Ryo

AU - Ogawa, Tsuneyoshi

AU - Wato, Masaki

AU - Takatani, Masahiro

AU - Matsubara, Minoru

AU - Kawai, Yoshinari

AU - Okada, Hiroyuki

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N2 - 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

AB - 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

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