Rectal Indomethacin Versus Rectal Indomethacin and Sublingual Nitrate for PEP Prevention

NCT04425993 | Unknown DMC

• 1 other identifier: KY20200522-4
• Study Type: interventional
• Target: 2,700
• Locations: 1 country
• Sites: 4

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

Keywords

ERCP; Post-ERCP pancreatitis; PEP; NSAIDs; indomethacin; nitrate

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Rate of moderate to severe PEP

  14 days

• Other adverse events

  14 days

Study Arms (4)

Rectal indomethacin and sublingual nitrate

EXPERIMENTAL

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.

Drug: Isosorbide Dinitrate 5 MG; Drug: Indomethacin 100 MG

Rectal indomethacin and sublingual placebo

ACTIVE COMPARATOR

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.

Drug: Indomethacin 100 MG; Drug: Sublingual Placebo

Rectal placebo and sublingual nitrate

ACTIVE COMPARATOR

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.

Drug: Isosorbide Dinitrate 5 MG; Drug: Rectal placebo

Rectal placebo and sublingual placebo

PLACEBO COMPARATOR

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.

Drug: Sublingual Placebo; Drug: Rectal placebo

Interventions

Isosorbide Dinitrate 5 MG DRUG

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

Rectal indomethacin and sublingual nitrate; Rectal placebo and sublingual nitrate

Indomethacin 100 MG DRUG

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

Rectal indomethacin and sublingual nitrate; Rectal indomethacin and sublingual placebo

Sublingual Placebo DRUG

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

Rectal indomethacin and sublingual placebo; Rectal placebo and sublingual placebo

Rectal placebo DRUG

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

Rectal placebo and sublingual nitrate; Rectal placebo and sublingual placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Air Force Military Medical University, China: lead

Study Sites (4)

Xiamen Humanity Hospital

Xiamen, Fujian, China

Location

Lanzhou University Second Hospital

Lanzhou, Gansu, 730030, China

Location

Xi'an Central Hospital

Xi'an, Shaanxi, 710032, China

Location

Xijing Hoapital

Xi'an, Shaanxi, 710032, China

Location

Related Publications (5)

• 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.

  PMID: 24513806 BACKGROUND

• 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.

  PMID: 30772342 BACKGROUND

• 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.

  PMID: 24098392 BACKGROUND

• 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.

  PMID: 27133971 BACKGROUND

• 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.

  PMID: 30391434 BACKGROUND

MeSH Terms

Interventions

Isosorbide Dinitrate; Indomethacin

Intervention Hierarchy (Ancestors)

Isosorbide; Sorbitol; Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associated professor

Study Record Dates

• First Submitted: June 8, 2020
• First Posted: June 11, 2020
• Study Start: July 1, 2020
• Primary Completion: May 30, 2022
• Study Completion: December 30, 2022
• Last Updated: October 22, 2020

Record last verified: 2020-10

Locations

CN (4)