Prevention of Post-ERCP Pancreatitis by Indomethacin vs Diclofenac

Sponsor

Air Force Military Medical University, China (Other)

Overall Status

Recruiting

CT.gov ID

NCT05947461

Collaborator

(none)

3,612

Enrollment

Locations

Arms

Anticipated Duration (Months)

328.4

Patients Per Site

13.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Post-ERCP Acute Pancreatitis NSAIDs Indomethacin Diclofenac Endoscopic Retrograde Cholangiopancreatography	Drug: 100mg diclofenac Drug: 100mg indomethacin	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

3612 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants in the interventional group received 100mg rectal dicfenacParticipants in the interventional group received 100mg rectal dicfenac

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jun 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Jun 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: diclofenac group Patients without contraindications in diclofenac group received 100mg rectal diclofenac 30 mins before ERCP procedure.	Drug: 100mg diclofenac All patients without contraindications should receive 100mg rectal diclofenac 30mins before ERCP procedure
Active Comparator: Indomethacin group Patients without contraindications in indomethacin group received 100mg rectal indomethacin 30 mins before ERCP procedure.	Drug: 100mg indomethacin All patients without contraindications should receive 100mg rectal indomethacin 30mins before ERCP procedure

Arm

Intervention/Treatment

Experimental: diclofenac group

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

Drug: 100mg diclofenac

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

Active Comparator: Indomethacin group

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

Drug: 100mg indomethacin

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

Outcome Measures

Primary Outcome Measures

Rate of post-ERCP Pancreatitis [30 days]
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.

Secondary Outcome Measures

Rate of 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 Overall ERCP-related complications [30 days]
ERCP-related complications include post-ERCP pancreatitis, gastrointestinal bleeding, perforation or infection according to Cotton Criteria.
Rate of patients with different severity of pancreatitis evaluated by revised Atlanta criteria [30 days]
Rate of NSAIDs-related complications [30 days]
NSAIDs-related complications include: acute kidney injury, allergic reaction, gastrointestinal bleeding, myocardial infarction, cerebrovascular accident, and death

Other Outcome Measures

Rate of ERCP-related perforation [30 days]
Perforation was established according to Cotton criteria
Rate of ERCP-related infection [30 days]
Infection was established according to Cotton criteria
Rate of ERCP-related bleeding [30 days]
Bleeding was established according to Cotton criteria
Rate of mortality [30 days]
Number of hospital days after ERCP [180 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of gastroenterology, Second Affiliated Hospital of Chongqing Medical University	Chongqing	Chongqing	China	400010
2	Department of Gastroenterology, Fujian Medical University Xiamen Humanity Hospital	Xiamen	Fujian	China	361000
3	Department of Gastroenterology, The 980th Hospital of the PLA Joint Logistics Support Force	Shijia Zhuang	Hebei	China	050000
4	Department of Gastroenterology, Huaihe Hospital of Henan University	Kaifeng	Henan	China	475000
5	Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University	Yinchuan	Ningxia	China	750004
6	The Second Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi	China	710000
7	Department of Gastroenterology,The 986th Hospital of Xijing Hospital	Xi'an	Shaanxi	China	710032
8	Xijing Hospital of Digestive Diseases, Air Force Military Medical University, China	Xi'an	Shaanxi	China	710032
9	Deparment of hepatobiliary surgery, The First Affiliated Hospital Of Xi'an Jiaotong University	Xi'an	Shaanxi	China	710061
10	Department of Gastroenterology and Endoscopy, Department of Gastroenterology and EndoscopyThe Third Affiliated Hospital of Naval Military Medical University	Shanghai	Shanghai	China	200000
11	Department of Gastroenterology, General Hospital of Xinjiang Military Region	Urumqi	Xinjiang	China	830000

Sponsors and Collaborators

Air Force Military Medical University, China

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Yanglin Pan, Professor, Air Force Military Medical University, China

ClinicalTrials.gov Identifier:

NCT05947461

Other Study ID Numbers:

KY20232165-C-1

First Posted:

Jul 17, 2023

Last Update Posted:

Jul 17, 2023

Last Verified:

Jul 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Pancreatitis

Diclofenac

Indomethacin

Study Results

No Results Posted as of Jul 17, 2023