Indomethacin vs Diclofenac for Preventing PEP

Not Applicable

Recruiting

• Conditions: ERCP; Pancreatitis; Non-steroidal Anti-inflammatory (NSAID); Indomethacin; Diclofenac
• Interventions: Drug: Indomethacin 100 MG; Drug: Diclofenac 100mg

• Registration Number: NCT07071441
• Lead Sponsor: Air Force Military Medical University, China

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-06
• Study Start: 2025-06-01
• Study First Submitted: 2025-07-08
• Study First Submitted QC: 2025-07-08
• Last Update Submitted: 2025-07-08
• Study First Posted: 2025-07-17
• Last Update Posted: 2025-07-17
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 4050

Inclusion Criteria

• 18-80 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Indomethacin	Indomethacin 100 MG	All patients without contraindications should receive 100mg rectal indomethacin within 30mins before ERCP procedure
Diclofenac group	Diclofenac 100mg	All patients without contraindications should receive 100mg rectal diclofenac within 30mins before ERCP procedure

Primary Outcome Measures

Name	Time	Method
Rate of post-ERCP Pancreatitis	30 days	a new or aggravated upper abdominal pain, with an elevated pancreatic enzyme of at least 3 times as the upper limit of normal value 24h after procedure and prolonged hospitalization days for at least 2 days. This definition was based on a widely recognized Cotton consensus

Secondary Outcome Measures

Name	Time	Method
Rate of mild, moderate or severe PEP	30 days	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.
Rate of patients with different severity of pancreatitis evaluated by revised Atlanta criteria	30 days	Mild: The most common form of acute pancreatitis, without organ failure or local or systemic complications, generally resolving within 1 week of onset.; Moderately Severe: the presence of transient organ failure, local complications or exacerbation of co-morbid disease.; Severe: persistent organ failure, that is, organ failure \>48 h. Local complications are peripancreatic fluid collections, pancreatic and peripancreatic necrosis (sterile or infected), pseudocyst and walled-off necrosis (sterile or infected).
Rate of ERCP-related perforation	30 days	Perforation was established according to Cotton criteria, Mild: slight leakage of fluid or contrast dye, manageable through fluid administration and suction therapy ≤3 days Moderate: definite perforation required to be managed for 4-10 days Severe: management for more than 10 days or requiring for percutaneous or surgical intervention.
Rate of ERCP-related infection	30 days	Infection was established according to Cotton criteria. Mild: temperature \>38℃ for 24-48h Moderate: Febrile illness requiring \>3 days of hospital treatment; endoscopic or percutaneous interventions; Severe: septic shock or requiring surgery.
Rate of ERCP-related bleeding	30 days	Bleeding was established according to Cotton criteria. Mild: a documented decrease in hemoglobin concentration by \<3 g/L, without requiring the blood transfusion; Moderate: blood transfusion ≤4 units; without need for angiographic or surgery interventions Severe: Transfusion: ≥5 units or requiring for angiographic or surgery interventions.
Rate of NSAIDs-related complications	30 days	NSAIDs-related complications include: acute kidney injury, allergic reaction, gastrointestinal bleeding, myocardial infarction, cerebrovascular accident, and death
Rate of mortality	30 days
The rate of total adverse events	30 days	Adverse events include ERCP-related or non ERCP-related adverse events

Trial Locations

Locations (20)

The first medical center, Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China

The Second Affiliated Hospital of Chongqing Medical University; 🇨🇳 Chongqing, Chongqing, China

Department of Gastroenterology, Hongai Hospital; 🇨🇳 Xiamen, Fujian, China

Harbin Medical University Affiliated Fourth Hospital; 🇨🇳 Harbin, Heilongjiang, China

Zhaolei181220@163.Com; 🇨🇳 Harbin, Heilongjiang, China

Huaihe Hospital of Henan University; 🇨🇳 Kaifeng, Hennan, China

Renmin hospital of Wuhan University; 🇨🇳 Wuhan, Hubei, China

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China

The Third Xiangya Hospital of Central South University; 🇨🇳 Changsha, Hunan, China

Jilin Miniciple People'S Hospital; 🇨🇳 Jilin, Jilin, China

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