Rectal Indomethacin Versus Rectal Indomethacin and Sublingual Nitrate for PEP Prevention

Post-ERCP Acute Pancreatitis Clinical Trial

Official title:

Rectal Indomethacin Versus Rectal Indomethacin and Sublingual Nitrate to Prevent Post-ERCP Pancreatitis: a Multicentre, Non-inferiority, Double-blind, Randomised Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04425993
• Other study ID #: KY20200522-4
• Status: Active, not recruiting
• Phase: N/A
• Start date: July 1, 2020
• Est. completion date: December 30, 2022

Study information

• Verified date: October 2020
• Source: Air Force Military Medical University, China
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) are at risk for post-ERCP pancreatitis (PEP), which is associated with adverse outcomes. Combination prophylaxis strategies are increasingly investigated to prevent PEP more effectively, and studies have confirmed the benefits. Two randomized controlled trials revealed that combination prophylaxis with rectal NSAIDs and sublingual nitrate has reduced PEP rates to 5.6%-6.7% in average-risk patients. However, there was concern regarding the safety of sublingual nitrate with reports of significant increasing the risk of hypotesion (rate of 54.9%) and headache (rate of 4.1%) as compared with placebo. As a safety drug, rectal administration of one dose NSAIDs is recommended as basic chemoprophylaxis in common or high-risk patients in guidelines. Results from previous studies showed rectal administration of NSAIDs significantly reduced PEP rate to 4-5.3% in average-risk patients. Although the difference in demographics, study design and outcomes definition, evidence was obtained that rectal NSAIDS was associated with similar PEP rate as combination prophylaxis with rectal NSAIDs and sublingual nitrate. However, evidence is lacking from large, randomized clinical trials indicating that efficiency of PEP prevention with rectal NSAIDs alone is not inferior to with combination prophylaxis. The investigators conduct this trial to investigate the hypothesis that rectal NSAIDs alone is non-inferior to the combination prophylaxis in terms of PEP prevention, but with reduce side effect.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2700
• Est. completion date: December 30, 2022
• Est. primary completion date: May 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients (age, 18-80 y) with native papilla planned for diagnostic or therapeutic ERCP were eligible for enrollment in the study.

Exclusion Criteria:

• contraindications to ERCP;
• allergy to nitrates or NSAIDs;
• currently on nitrate medication;
• receiving NSAIDs within 7 days;
• not suitable for indomethacin eg, gastrointestinal hemorrhage within the past 4 weeks, renal dysfunction (creatinine level >1.4 mg/dL) or the presence of coagulopathy before the procedure (international normalized ratio > 1.5);
• acute pancreatitis within 3 days;
• pregnant or breastfeeding women;
• unwilling or inability to provide consent.

Related Conditions & MeSH terms

• Pancreatitis
• Post-ERCP Acute Pancreatitis

Intervention

Drug:
• Isosorbide Dinitrate 5 MG
All patients without contraindications should receive sublingual isosorbide dinitrate tablet within 5 minutes before ERCP.
• Indomethacin 100 MG
All patients without contraindications should receive rectal indomethacin within 30 min before ERCP.
• Sublingual Placebo
All patients without contraindications should receive sublingual placebo within 5 minutes before ERCP.
• Rectal placebo
All patients without contraindications should receive rectal placebo within 30 min before ERCP.

Locations

Country	Name	City	State
China	Lanzhou University Second Hospital	Lanzhou	Gansu
China	Xi'an Central Hospital	Xi'an	Shaanxi
China	Xijing Hoapital	Xi'an	Shaanxi
China	Xiamen Humanity Hospital	Xiamen	Fujian

Sponsors (1)

Lead Sponsor	Collaborator
Air Force Military Medical University, China

Country where clinical trial is conducted

China, 

References & Publications (5)

Ding J, Jin X, Pan Y, Liu S, Li Y. Glyceryl trinitrate for prevention of post-ERCP pancreatitis and improve the rate of cannulation: a meta-analysis of prospective, randomized, controlled trials. PLoS One. 2013 Oct 1;8(10):e75645. doi: 10.1371/journal.pone.0075645. eCollection 2013. — View Citation

Luo H, Wang X, Zhang R, Liang S, Kang X, Zhang X, Lou Q, Xiong K, Yang J, Si L, Liu W, Liu Y, Zhou Y, Wang S, Yang M, Chen W, Han Y, Shang G, Yang X, He Y, Zou Q, Guo W, Dai Y, Zeng W, Zhu X, Gong R, Li X, Nie Z, Wang Q, Wang L, Pan Y, Guo X, Fan D. Rectal Indomethacin and Spraying of Duodenal Papilla With Epinephrine Increases Risk of Pancreatitis Following Endoscopic Retrograde Cholangiopancreatography. Clin Gastroenterol Hepatol. 2019 Jul;17(8):1597-1606.e5. doi: 10.1016/j.cgh.2018.10.043. Epub 2018 Oct 31. — View Citation

Luo H, Zhao L, Leung J, Zhang R, Liu Z, Wang X, Wang B, Nie Z, Lei T, Li X, Zhou W, Zhang L, Wang Q, Li M, Zhou Y, Liu Q, Sun H, Wang Z, Liang S, Guo X, Tao Q, Wu K, Pan Y, Guo X, Fan D. Routine pre-procedural rectal indometacin versus selective post-procedural rectal indometacin to prevent pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography: a multicentre, single-blinded, randomised controlled trial. Lancet. 2016 Jun 4;387(10035):2293-2301. doi: 10.1016/S0140-6736(16)30310-5. Epub 2016 Apr 28. — View Citation

Sotoudehmanesh R, Eloubeidi MA, Asgari AA, Farsinejad M, Khatibian M. A randomized trial of rectal indomethacin and sublingual nitrates to prevent post-ERCP pancreatitis. Am J Gastroenterol. 2014 Jun;109(6):903-9. doi: 10.1038/ajg.2014.9. Epub 2014 Feb 11. — View Citation

Tomoda T, Kato H, Ueki T, Akimoto Y, Hata H, Fujii M, Harada R, Ogawa T, Wato M, Takatani M, Matsubara M, Kawai Y, Okada H. Combination of Diclofenac and Sublingual Nitrates Is Superior to Diclofenac Alone in Preventing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography. Gastroenterology. 2019 May;156(6):1753-1760.e1. doi: 10.1053/j.gastro.2019.01.267. Epub 2019 Feb 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of post-ERCP Pancreatitis	The diagnosis of PEP was established if there was new onset of upper abdominal pain associated with an increased amylase or lipase level of at least 3 times the upper limit of normal range at 24 hours after the procedure, and hospitalization for at least 2 nights. Doctors are advised to use cross-sectional imaging to identify ambiguous PEP.	14 days
Secondary	Rate of moderate to severe PEP	The severity classification of pancreatitis was defined according to the criteria of Cotton et al and the revised Atlanta criteria.	14 days
Secondary	Other adverse events	Adverse effects of indomethacin, including gastrointestinal bleeding and renal failure.; Adverse effects of nitrates, including hypotension, headache and dizziness. Other post-ERCP adverse events including cholangitis, bleeding, and perforation.; Any other adverse outcomes possibly related to ERCP or experimental drugs that required hospital admission or a prolonged hospital stay for further management.	14 days