Prevention of Post-ERCP Pancreatitis by Indomethacin Vs Diclofenac

NCT05947461 | Terminated DMC

• 1 other identifier: KY20232165-C-1
• Study Type: interventional
• Target: 1,204
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Post-ERCP Acute Pancreatitis; NSAIDs; Indomethacin; Diclofenac; Endoscopic Retrograde Cholangiopancreatography

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Rate of moderate or severe PEP

  30 days

• Rate of Overall ERCP-related complications

  30 days

• Rate of patients with different severity of pancreatitis evaluated by revised Atlanta criteria

  30 days

• Rate of NSAIDs-related complications

  30 days

Other Outcomes (5)

• Rate of ERCP-related perforation

  30 days

• Rate of ERCP-related infection

  30 days

• Rate of ERCP-related bleeding

  30 days

Study Arms (2)

diclofenac group

EXPERIMENTAL

Patients without contraindications in diclofenac group received 100mg rectal diclofenac 30 mins before ERCP procedure.

Drug: 100mg diclofenac

Indomethacin group

ACTIVE COMPARATOR

Patients without contraindications in indomethacin group received 100mg rectal indomethacin 30 mins before ERCP procedure.

Drug: 100mg indomethacin

Interventions

100mg diclofenac DRUG

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

diclofenac group

100mg indomethacin DRUG

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

Indomethacin group

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old patients planned to undergo ERCP

You may not qualify if:

• 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

Sponsors & Collaborators

• Air Force Military Medical University, China: lead

Study Sites (11)

Department of gastroenterology, Second Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400010, China

Location

Department of Gastroenterology, Fujian Medical University Xiamen Humanity Hospital

Xiamen, Fujian, 361000, China

Location

Department of Gastroenterology, The 980th Hospital of the PLA Joint Logistics Support Force

Shijiazhuang, Hebei, 050000, China

Location

Department of Gastroenterology, Huaihe Hospital of Henan University

Kaifeng, Henan, 475000, China

Location

Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University

Yinchuan, Ningxia, 750004, China

Location

The Second Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710000, China

Location

Department of Gastroenterology,The 986th Hospital of Xijing Hospital

Xi'an, Shaanxi, 710032, China

Location

Xijing Hospital of Digestive Diseases, Air Force Military Medical University, China

Xi'an, Shaanxi, 710032, China

Location

Deparment of hepatobiliary surgery, The First Affiliated Hospital Of Xi'an Jiaotong University

Xi'an, Shaanxi, 710061, China

Location

Department of Gastroenterology and Endoscopy, Department of Gastroenterology and EndoscopyThe Third Affiliated Hospital of Naval Military Medical University

Shanghai, Shanghai Municipality, 200000, China

Location

Department of Gastroenterology, General Hospital of Xinjiang Military Region

Ürümqi, Xinjiang, 830000, China

Location

Related Publications (6)

• 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.

  PMID: 2070995 BACKGROUND

• 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 consensus. Gut. 2013 Jan;62(1):102-11. doi: 10.1136/gutjnl-2012-302779. Epub 2012 Oct 25.

  PMID: 23100216 BACKGROUND

• 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):2380-2389. doi: 10.1007/s11605-022-05399-6. Epub 2022 Aug 8.

  PMID: 35941494 BACKGROUND

• 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, intravenous fluids, pancreatic stents, or their combinations for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol. 2021 Sep;6(9):733-742. doi: 10.1016/S2468-1253(21)00170-9. Epub 2021 Jun 30.

  PMID: 34214449 BACKGROUND

• 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-procedural rectal indometacin to prevent pancreatitis in patients undergoing endoscopic retrograde cholangiopancreatography: a multicentre, single-blinded, randomised controlled trial. Lancet. 2016 Jun 4;387(10035):2293-2301. doi: 10.1016/S0140-6736(16)30310-5. Epub 2016 Apr 28.

  PMID: 27133971 BACKGROUND

• Kang X, Xia M, Wang J, Wang X, Luo H, Qin W, Liang Z, Zhao G, Yang L, Sun H, Tao J, Ning B, Zhong L, Zhang R, Ma X, Zhao J, Yue L, Jin H, Kang C, Ren G, Liang S, Wang H, Wang L, Nie Y, Wu K, Fan DM, Pan Y. Rectal diclofenac versus indomethacin for prevention of post-ERCP pancreatitis (DIPPP): a multicentre, double-blind, randomised, controlled trial. Gut. 2025 Jun 6;74(7):1094-1102. doi: 10.1136/gutjnl-2024-334466.

  PMID: 40113243 DERIVED

MeSH Terms

Interventions

Diclofenac; Indomethacin

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Participants in the interventional group received 100mg rectal dicfenac

Study Record Dates

• First Submitted: June 20, 2023
• First Posted: July 17, 2023
• Study Start: June 1, 2023
• Primary Completion: June 22, 2024
• Study Completion: June 22, 2024
• Last Updated: October 28, 2024

Record last verified: 2023-07

Locations

CN (11)