Prevention of Post-ERCP Pancreatitis by Indomethacin vs Diclofenac

Post-ERCP Acute Pancreatitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05947461
• Other study ID #: KY20232165-C-1
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2023
• Est. completion date: June 1, 2025

Study information

• Verified date: July 2023
• Source: Air Force Military Medical University, China
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3612
• Est. completion date: June 1, 2025
• Est. primary completion date: March 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Endoscopic Retrograde Cholangiopancreatography
• Indomethacin
• NSAIDs
• Pancreatitis
• Post-ERCP Acute Pancreatitis

Intervention

Drug:
• 100mg diclofenac
All patients without contraindications should receive 100mg rectal diclofenac 30mins before ERCP procedure
• 100mg indomethacin
All patients without contraindications should receive 100mg rectal indomethacin 30mins before ERCP procedure

Locations

Country	Name	City	State
China	Department of gastroenterology, Second Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing
China	Department of Gastroenterology, Huaihe Hospital of Henan University	Kaifeng	Henan
China	Department of Gastroenterology and Endoscopy, Department of Gastroenterology and EndoscopyThe Third Affiliated Hospital of Naval Military Medical University	Shanghai	Shanghai
China	Department of Gastroenterology, The 980th Hospital of the PLA Joint Logistics Support Force	Shijia Zhuang	Hebei
China	Department of Gastroenterology, General Hospital of Xinjiang Military Region	Urumqi	Xinjiang
China	Deparment of hepatobiliary surgery, The First Affiliated Hospital Of Xi'an Jiaotong University	Xi'an	Shaanxi
China	Department of Gastroenterology,The 986th Hospital of Xijing Hospital	Xi'an	Shaanxi
China	The Second Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi
China	Xijing Hospital of Digestive Diseases, Air Force Military Medical University, China	Xi'an	Shaanxi
China	Department of Gastroenterology, Fujian Medical University Xiamen Humanity Hospital	Xiamen	Fujian
China	Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University	Yinchuan	Ningxia

Sponsors (1)

Lead Sponsor	Collaborator
Air Force Military Medical University, China

Country where clinical trial is conducted

China, 

References & Publications (5)

Akshintala VS, Sperna Weiland CJ, Bhullar FA, Kamal A, Kanthasamy K, Kuo A, Tomasetti C, Gurakar M, Drenth JPH, Yadav D, Elmunzer BJ, Reddy DN, Goenka MK, Kochhar R, Kalloo AN, Khashab MA, van Geenen EJM, Singh VK. Non-steroidal anti-inflammatory drugs, i — View Citation

Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, Tsiotos GG, Vege SS; Acute Pancreatitis Classification Working Group. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international con — View Citation

Cotton PB, Lehman G, Vennes J, Geenen JE, Russell RC, Meyers WC, Liguory C, Nickl N. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc. 1991 May-Jun;37(3):383-93. doi: 10.1016/s0016-5107(91)70740-2. — View Citation

Kang X, Guo X, Chen Z, Zhou Z, Luo H, Lu Y, Lou L, Guo X, Pan Y. The Incidence and Severity of Post-ERCP Pancreatitis in Patients Receiving Standard Administration of NSAIDs: a Systematic Review and Meta-analysis. J Gastrointest Surg. 2022 Nov;26(11):2380 — View Citation

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-proc — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Rate of ERCP-related perforation	Perforation was established according to Cotton criteria	30 days
Other	Rate of ERCP-related infection	Infection was established according to Cotton criteria	30 days
Other	Rate of ERCP-related bleeding	Bleeding was established according to Cotton criteria	30 days
Other	Rate of mortality		30 days
Other	Number of hospital days after ERCP		180 days
Primary	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	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
Secondary	Rate of Overall ERCP-related complications	ERCP-related complications include post-ERCP pancreatitis, gastrointestinal bleeding, perforation or infection according to Cotton Criteria.	30 days
Secondary	Rate of patients with different severity of pancreatitis evaluated by revised Atlanta criteria		30 days
Secondary	Rate of NSAIDs-related complications	NSAIDs-related complications include: acute kidney injury, allergic reaction, gastrointestinal bleeding, myocardial infarction, cerebrovascular accident, and death	30 days