Rectal Indomethacin Versus Rectal Indomethacin and Sublingual Nitrate for PEP Prevention

NCT ID: NCT04425993

Last Updated: 2020-10-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 2700 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-01
• Study Completion Date: 2022-12-30

Brief 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.

Conditions

Post-ERCP Acute Pancreatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Rectal indomethacin and sublingual nitrate

All patients without contraindications should receive sublingual isosorbide dinitrate within 5 min before ERCP.

All patients without contraindications should receive rectal indomethacin within 30 min before ERCP.

Group Type: EXPERIMENTAL

Isosorbide Dinitrate 5 MG

Intervention Type: DRUG

All patients without contraindications should receive sublingual isosorbide dinitrate tablet within 5 minutes before ERCP.

Indomethacin 100 MG

Intervention Type: DRUG

All patients without contraindications should receive rectal indomethacin within 30 min before ERCP.

Rectal indomethacin and sublingual placebo

All patients without contraindications should receive sublingual placebo within 5 min before ERCP.

All patients without contraindications should receive rectal indomethacin within 30 min before ERCP.

Group Type: ACTIVE_COMPARATOR

Indomethacin 100 MG

Intervention Type: DRUG

All patients without contraindications should receive rectal indomethacin within 30 min before ERCP.

Sublingual Placebo

Intervention Type: DRUG

All patients without contraindications should receive sublingual placebo within 5 minutes before ERCP.

Rectal placebo and sublingual nitrate

All patients without contraindications should receive sublingual isosorbide dinitrate within 5 min before ERCP.

All patients without contraindications should receive rectal placebo within 30 min before ERCP.

Group Type: ACTIVE_COMPARATOR

Isosorbide Dinitrate 5 MG

Intervention Type: DRUG

All patients without contraindications should receive sublingual isosorbide dinitrate tablet within 5 minutes before ERCP.

Rectal placebo

Intervention Type: DRUG

All patients without contraindications should receive rectal placebo within 30 min before ERCP.

Rectal placebo and sublingual placebo

All patients without contraindications should receive sublingual placebo within 5 min before ERCP.

All patients without contraindications should receive rectal placebo within 30 min before ERCP.

Group Type: PLACEBO_COMPARATOR

Sublingual Placebo

Intervention Type: DRUG

All patients without contraindications should receive sublingual placebo within 5 minutes before ERCP.

Rectal placebo

Intervention Type: DRUG

All patients without contraindications should receive rectal placebo within 30 min before ERCP.

Interventions

Isosorbide Dinitrate 5 MG

All patients without contraindications should receive sublingual isosorbide dinitrate tablet within 5 minutes before ERCP.

Intervention Type: DRUG

Indomethacin 100 MG

All patients without contraindications should receive rectal indomethacin within 30 min before ERCP.

Intervention Type: DRUG

Sublingual Placebo

All patients without contraindications should receive sublingual placebo within 5 minutes before ERCP.

Intervention Type: DRUG

Rectal placebo

All patients without contraindications should receive rectal placebo within 30 min before ERCP.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Air Force Military Medical University, China

OTHER

Sponsor Role: lead

Responsible Party

Yanglin Pan

Associated professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Xiamen Humanity Hospital

Xiamen, Fujian, China

Lanzhou University Second Hospital

Lanzhou, Gansu, China

Xi'an Central Hospital

Xi'an, Shaanxi, China

Xijing Hoapital

Xi'an, Shaanxi, China

Countries

China

References

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.

Reference Type: BACKGROUND

PMID: 24513806 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30772342 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24098392 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27133971 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30391434 (View on PubMed)

Other Identifiers

KY20200522-4

Identifier Type: -

Identifier Source: org_study_id