Post-ERCP Acute PancreatitisNCT05947461
Prevention of Post-ERCP Pancreatitis by Indomethacin vs Diclofenac
A study testing 100mg diclofenac and 100mg indomethacin in people with Post-ERCP Acute Pancreatitis and NSAIDs, run by Air Force Military Medical University, China at 11 sites in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Post-ERCP Acute Pancreatitis, NSAIDs, Indomethacin
- What is being tested?
- 100mg diclofenac and 100mg indomethacin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,204 participants
- Where
- 11 sitesChina
- Study dates
- 1 Jun 2023to 22 Jun 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-90 years old patients planned to undergo ERCP
Who cannot join
- 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
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
China11 sites
Department of gastroenterology, Second Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, 400010
Department of Gastroenterology, Huaihe Hospital of Henan University
Kaifeng, Henan, 475000
Department of Gastroenterology and Endoscopy, Department of Gastroenterology and EndoscopyThe Third Affiliated Hospital of Naval Military Medical University
Shanghai, Shanghai Municipality, 200000
Department of Gastroenterology, The 980th Hospital of the PLA Joint Logistics Support Force
Shijiazhuang, Hebei, 050000
Department of Gastroenterology, General Hospital of Xinjiang Military Region
Ürümqi, Xinjiang, 830000
The Second Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, 710000
Department of Gastroenterology,The 986th Hospital of Xijing Hospital
Xi'an, Shaanxi, 710032
Xijing Hospital of Digestive Diseases, Air Force Military Medical University, China
Xi'an, Shaanxi, 710032
Deparment of hepatobiliary surgery, The First Affiliated Hospital Of Xi'an Jiaotong University
Xi'an, Shaanxi, 710061
Department of Gastroenterology, Fujian Medical University Xiamen Humanity Hospital
Xiamen, Fujian, 361000
Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University
Yinchuan, Ningxia, 750004
About this study
Official title: Rectal Disclofenac Versus Indomethacin for Prevention of Post-ERCP Pancreatitis (DIPPP): A Multicentre, Double-blind, Randomised, Controlled Trial
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
- Being tested
- 100mg diclofenac, 100mg indomethacin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
100mg diclofenacDrug
All patients without contraindications should receive 100mg rectal diclofenac 30mins before ERCP procedure
100mg indomethacinDrug
All patients without contraindications should receive 100mg rectal indomethacin 30mins before ERCP procedure
| Study group | Role | What they receive |
|---|---|---|
| diclofenac group | Experimental | Patients without contraindications in diclofenac group received 100mg rectal diclofenac 30 mins before ERCP procedure. Receives: Drug: 100mg diclofenac |
| Indomethacin group | Active comparator | Patients without contraindications in indomethacin group received 100mg rectal indomethacin 30 mins before ERCP procedure. Receives: Drug: 100mg indomethacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 days
Secondary outcomes (4)
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.
Measured: 30 days
Rate of Overall ERCP-related complications
ERCP-related complications include post-ERCP pancreatitis, gastrointestinal bleeding, perforation or infection according to Cotton Criteria.
Measured: 30 days
Rate of patients with different severity of pancreatitis evaluated by revised Atlanta criteria
Measured: 30 days
Rate of NSAIDs-related complications
NSAIDs-related complications include: acute kidney injury, allergic reaction, gastrointestinal bleeding, myocardial infarction, cerebrovascular accident, and death
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2023
- Study start1 Jun 2023
- Primary completion22 Jun 2024
- Study completion22 Jun 2024
Why it stopped: The data from the interim analysis showed a opposite trend predicting possible of benefit of indomethacin and conditional power analysis revealed a low probability of confirming the benefit of diclofenac if this trial will be continued.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Post-ERCP Acute PancreatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants in the interventional group received 100mg rectal dicfenac
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,204 participants (actual)
Sponsor and investigators
- Lead sponsor
- Air Force Military Medical University, China
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yanglin Pan, Air Force Military Medical University, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05947461
- Sponsor's protocol ID
- KY20232165-C-1
- Status last verified
- Jul 2023
- First submitted
- 20 Jun 2023
- Last updated
- 28 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 2070995Banks 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.
PubMed 23100216Kang 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.
PubMed 35941494Akshintala 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.
PubMed 34214449Luo 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.
PubMed 27133971Kang 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.
PubMed 40113243
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rectal Disclofenac Versus Indomethacin for Prevention of Post-ERCP Pancreatitis (DIPPP): A Multicentre, Double-blind, Randomised, Controlled Trial
- ClinicalTrials.gov ID
- NCT05947461
- Acronym / sponsor ID
- KY20232165-C-1
- Conditions
- Post-ERCP Acute Pancreatitis, NSAIDs, Indomethacin, Diclofenac, Endoscopic Retrograde Cholangiopancreatography
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The data from the interim analysis showed a opposite trend predicting possible of benefit of indomethacin and conditional power analysis revealed a low probability of confirming the benefit of diclofenac if this trial will be continued.
- Enrolment
- 1,204 participants (actual)
- Lead sponsor
- Air Force Military Medical University, ChinaUniversity, hospital or other
- Study start
- 1 Jun 2023 (actual)
- Primary completion
- 22 Jun 2024 (actual)
- Study completion
- 22 Jun 2024 (actual)
- First posted
- 17 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants in the interventional group received 100mg rectal dicfenac
| Arm | Type | Receives |
|---|---|---|
| diclofenac group | Experimental | Drug: 100mg diclofenacPatients without contraindications in diclofenac group received 100mg rectal diclofenac 30 mins before ERCP procedure. |
| Indomethacin group | Active comparator | Drug: 100mg indomethacinPatients without contraindications in indomethacin group received 100mg rectal indomethacin 30 mins before ERCP procedure. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 18-90 years old patients planned to undergo ERCP
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 100mg diclofenacAll patients without contraindications should receive 100mg rectal diclofenac 30mins before ERCP procedure | Drug | diclofenac group |
| 100mg indomethacinAll patients without contraindications should receive 100mg rectal indomethacin 30mins before ERCP procedure | Drug | Indomethacin group |
Primary outcome
Rate of post-ERCP Pancreatitis
Time frame: 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.
4 secondary outcomes
Rate of moderate or severe PEP
Time frame: 30 days
Rate of Overall ERCP-related complications
Time frame: 30 days
Rate of patients with different severity of pancreatitis evaluated by revised Atlanta criteria
Time frame: 30 days
Rate of NSAIDs-related complications
Time frame: 30 days
Results and safety
The study was stopped early (reason given: The data from the interim analysis showed a opposite trend predicting possible of benefit of indomethacin and conditional power analysis revealed a low probability of confirming the benefit of diclofenac if this trial will be continued.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2024.
- Results publication: PubMed 2070995Cotton 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.
- Results publication: PubMed 23100216Banks 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.
- Results publication: PubMed 35941494Kang 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.
- Results publication: PubMed 34214449Akshintala 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.
- Results publication: PubMed 27133971Luo 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.
- Derived from this study: PubMed 40113243Kang 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 100mg diclofenac and 100mg indomethacin in people with Post-ERCP Acute Pancreatitis and NSAIDs, run by Air Force Military Medical University, China at 11 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: The data from the interim analysis showed a opposite trend predicting possible of benefit of indomethacin and conditional power analysis revealed a low probability of confirming the benefit of diclofenac if this trial will be continued.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of post-ERCP Pancreatitis (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05947461, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2024.