Prevention of Post-ERCP Pancreatitis by Indomethacin vs Diclofenac

Study Overview
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Brief Summary
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Post-ERCP pancreatitis (PEP) is the most common complication after ERCP, which was associated with occasional mortality, prolonged hospital days and increased health costs. Some studies investigated the effectiveness of different Nonsteroidal antiinflammatory drugs (NSAIDs) for prevent PEP. However, several high-quality RCTs and meta-analyses consistently demonstrated only100mg rectal indomethacin or diclofenac significantly reduced PEP incidence compared with placebos. Thus, European Society of Gastrointestinal Endoscopy, American Society for Gastrointestinal Endoscopy and Japanese Society of Hepato-Biliary-Pancreatic surgery guidelines recommended rountine administration of 100mg rectal indomethacin or diclofenac in unselected patients who underwent ERCP. Up to date, the mechanisms of NSAIDs in preventing pancreatitis were not fully elucidated. Diclofenac and Indomethacin showed similar inhibitory effects in phospholipase A2 and cyclooxygenase pathways. And the peak concentration of diclofenac and indomethacin both occurs between 30 and 90 min after rectal administration. However, diclofenac may be a stronger inhibitor of other pancreatitis-related imflammatory siginals (e.g. nuclear factor kappa-B) than indomethacin. Recently, several meta-analyses found 100mg rectal diclofenac to be more efficacious than 100mg rectal indomethacin. Despite these data, there is no conclusive evidence to prove that rectal diclofenac could provide incremental benefits over indomethacin from high-quality randomized, controlled trials. Therefore, the investigators conducted a multicenter, double-blind, randomized, controlled clinical trial to evaluate the efficacy of rectal diclofenac versus indomethacin for the prevention of post-ERCP pancreatitis in average-risk patients.

Official Title
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Rectal Disclofenac Versus Indomethacin for Prevention of Post-ERCP Pancreatitis (DIPPP): A Multicentre, Double-blind, Randomised, Controlled Trial

Conditions
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Post-ERCP Acute Pancreatitis, NSAIDs, Indomethacin, Diclofenac, Endoscopic Retrograde Cholangiopancreatography

Intervention / Treatment
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* Drug: 100mg diclofenac
* Drug: 100mg indomethacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-90 years old patients planned to undergo ERCP Exclusion Criteria: Allergy to NSAIDs The administration of NSAIDs within 7 days Not suitable for NSAIDs administration (gastrointestinal hemorrhage within 4 weeks, renal dysfunction [Cr >1.4mg/dl=120umol/l]; presence of coagulopathy before the procedure) Previous biliary sphincterotomy and papillary large balloon dilation Acute pancreatitis within 3 days before ERCP Hemodynamical instability Pregnancy or lactation Unable to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants in the interventional group received 100mg rectal dicfenac
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: diclofenac group<br>Patients without contraindications in diclofenac group received 100mg rectal diclofenac 30 mins before ERCP procedure. | Drug: 100mg diclofenac<br>* All patients without contraindications should receive 100mg rectal diclofenac 30mins before ERCP procedure<br>|
| Active Comparator: Indomethacin group<br>Patients without contraindications in indomethacin group received 100mg rectal indomethacin 30 mins before ERCP procedure. | Drug: 100mg indomethacin<br>* All patients without contraindications should receive 100mg rectal indomethacin 30mins before ERCP procedure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of post-ERCP Pancreatitis | The diagnosis of post-ERCP pancreatitis was confirmed 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 ERCP, accompanied with extension of hospitalization for at least 2 nights. | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of moderate or severe PEP | The severity classification of post-ERCP pancreatitis was defined according to the Cotton Criteria. Mild PEP: with an extension of hospitalization period of 2-3 days; Moderate PEP: with an extension of hospitalization period of 4-10 days; Severe PEP: with an extension of more than 10 days, or hemorrhagic pancreatitis, phlegmon, or pseudocyst, intervention (percutaneous drainage or surgery), or death. | 30 days | 
| Rate of Overall ERCP-related complications | ERCP-related complications include post-ERCP pancreatitis, gastrointestinal bleeding, perforation or infection according to Cotton Criteria. | 30 days | 
| Rate of patients with different severity of pancreatitis evaluated by revised Atlanta criteria |  | 30 days | 
| Rate of NSAIDs-related complications | NSAIDs-related complications include: acute kidney injury, allergic reaction, gastrointestinal bleeding, myocardial infarction, cerebrovascular accident, and death | 30 days |