Indomethacin vs Diclofenac for Preventing PEP

Air Force Military Medical University of People's Liberation Army

Status: Enrolling

Conditions: Diclofenac; ERCP; Pancreatitis; Non-steroidal Anti-inflammatory (NSAID); Indomethacin

Treatments: Drug: Diclofenac 100mg; Drug: Indomethacin 100 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT07071441

KY20242439-F-1

Details and patient eligibility

About

Pancreatitis is the most common and serious complication following post-endoscopic retrograde cholangiopancreatography (ERCP) and is associated with occasional mortality, extended hospital stays, and increased healthcare expenses. Preprocedural administration of rectal non-steroidal anti-inflammatory drugs (NSAIDs) was demonstrated to be an effective and convenient strategy for post-ERCP pancreatitis (PEP). Furthermore, several meta-analyses found that only 100mg indomethacin and diclofenac could effectively reduce PEP. Therefore, updated international clinical practice guidelines uniformly recommended administration of 100mg indomethacin or diclofenac in patients without contradictions. However, it was unclear which one of the two drug is more superior.

A recent meta-analysis suggested 100mg rectal diclofenac was more efficacious than same-dose rectal indomethacin in PEP prevention (relative risk (RR) 0·59, 95% confidence intervals (CI) 0·40-0·89). Based on the results, we conducted a multicenter, double-blind, control trial to investigate whether 100mg diclofenac is superior than same-dose indomethacin. This trial planned to enroll 3612 patients in total. However, in the first interim analysis, PEP occurred in 53 patients (8.8%) of 600 patients allocated to diclofenac group and 37 patients (6.1%) of 604 patients allocated to indomethacin group (relative risk (RR) 1.44; 95% confidence interval (CI) 0.96-2.16, p=0.074). Thus, the trial was stopped according to the futility rule of conditional power. However, it was worth noticing that PEP tended to be higher in diclofenac group than that in indomethacin group. A sample size of 1204 was under power to draw the conclusion of significantly lower PEP rate in indomethacin group and thus a new trial with larger sample size of sufficient power is predicted to prove the superiority of indomethacin over diclofenac. Here we conducted a multicenter, randomized, double-blind trial to investigate whether 100mg indomethacin is superior to 100mg diclofenac in preventing PEP.

Enrollment: 4,050 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 18-90 years old patients with native papilla who planned to undergo ERCP

Exclusion criteria

• Previous biliary sphincterotomy and papillary large balloon dilation
• Planned for placements of pancreatic duct stents (eg. pancreatic duct strictures, planned ampullectomy)
• 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)
• Acute pancreatitis within 7 days before ERCP or acute pancreatitis with obvious Pancreatic edema and peripancreatic fluid collections
• Hemodynamical instability
• Pregnancy or lactation
• Unable to give informed consent

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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4,050 participants in 2 patient groups

Indomethacin

Experimental group

Description:

All patients without contraindications should receive 100mg rectal indomethacin within 30mins before ERCP procedure

Treatment:

Drug: Indomethacin 100 MG

Diclofenac group

Active Comparator group

Description:

All patients without contraindications should receive 100mg rectal diclofenac within 30mins before ERCP procedure

Treatment:

Drug: Diclofenac 100mg