Rectal Indomethacin Versus Rectal Indomethacin and Sublingual Nitrate for PEP Prevention

Air Force Military Medical University of People's Liberation Army

Status: Unknown

Conditions: Post-ERCP Acute Pancreatitis

Treatments: Drug: Rectal placebo; Drug: Isosorbide Dinitrate 5 MG; Drug: Indomethacin 100 MG; Drug: Sublingual Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04425993

KY20200522-4

Details and patient eligibility

About

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.

Enrollment: 2,700 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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2,700 participants in 4 patient groups, including a placebo group

Rectal indomethacin and sublingual nitrate

Experimental group

Description:

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.

Treatment:

Drug: Isosorbide Dinitrate 5 MG

Drug: Indomethacin 100 MG

Rectal indomethacin and sublingual placebo

Active Comparator group

Description:

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.

Treatment:

Drug: Sublingual Placebo

Drug: Indomethacin 100 MG

Rectal placebo and sublingual nitrate

Active Comparator group

Description:

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.

Treatment:

Drug: Isosorbide Dinitrate 5 MG

Drug: Rectal placebo

Rectal placebo and sublingual placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Sublingual Placebo

Drug: Rectal placebo