Post-ERCP Acute PancreatitisNCT04425993
Rectal Indomethacin Versus Rectal Indomethacin and Sublingual Nitrate for PEP Prevention
A study testing Isosorbide Dinitrate 5 MG and Indomethacin 100 MG in people with Post-ERCP Acute Pancreatitis, run by Air Force Military Medical University, China at 4 sites in China.
Trial summary
Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) are at risk for post-ERCP pancreatitis (PEP), which is associated with adverse outcomes. Combination prophylaxis strategies are increasingly investigated to prevent PEP more effectively, and studies have confirmed the benefits. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Post-ERCP Acute Pancreatitis
- What is being tested?
- Isosorbide Dinitrate 5 MG and Indomethacin 100 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,700 participants
- Where
- 4 sitesChina
- Study dates
- 1 Jul 2020to 30 Dec 2022
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients (age, 18-80 y) with native papilla planned for diagnostic or therapeutic ERCP were eligible for enrollment in the study.
Who cannot join
- contraindications to ERCP;
- allergy to nitrates or NSAIDs;
- currently on nitrate medication;
- receiving NSAIDs within 7 days;
- not suitable for indomethacin eg, gastrointestinal hemorrhage within the past 4 weeks, renal dysfunction (creatinine level >1.4 mg/dL) or the presence of coagulopathy before the procedure (international normalized ratio > 1.5);
- acute pancreatitis within 3 days;
- pregnant or breastfeeding women;
- unwilling or inability to provide consent.
Trial locations and contacts
4 sites in 1 country.
China4 sites
Lanzhou University Second Hospital
Lanzhou, Gansu, 730030
Xi'an Central Hospital
Xi'an, Shaanxi, 710032
Xijing Hoapital
Xi'an, Shaanxi, 710032
Xiamen Humanity Hospital
Xiamen, Fujian
About this study
Official title: Rectal Indomethacin Versus Rectal Indomethacin and Sublingual Nitrate to Prevent Post-ERCP Pancreatitis: a Multicentre, Non-inferiority, Double-blind, Randomised Trial
Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) are at risk for post-ERCP pancreatitis (PEP), which is associated with adverse outcomes. Combination prophylaxis strategies are increasingly investigated to prevent PEP more effectively, and studies have confirmed the benefits. Two randomized controlled trials revealed that combination prophylaxis with rectal NSAIDs and sublingual nitrate has reduced PEP rates to 5.6%-6.7% in average-risk patients. However, there was concern regarding the safety of sublingual nitrate with reports of significant increasing the risk of hypotesion (rate of 54.9%) and headache (rate of 4.1%) as compared with placebo.
As a safety drug, rectal administration of one dose NSAIDs is recommended as basic chemoprophylaxis in common or high-risk patients in guidelines. Results from previous studies showed rectal administration of NSAIDs significantly reduced PEP rate to 4-5.3% in average-risk patients. Although the difference in demographics, study design and outcomes definition, evidence was obtained that rectal NSAIDS was associated with similar PEP rate as combination prophylaxis with rectal NSAIDs and sublingual nitrate. However, evidence is lacking from large, randomized clinical trials indicating that efficiency of PEP prevention with rectal NSAIDs alone is not inferior to with combination prophylaxis. The investigators conduct this trial to investigate the hypothesis that rectal NSAIDs alone is non-inferior to the combination prophylaxis in terms of PEP prevention, but with reduce side effect.
- Conditions
- Post-ERCP Acute Pancreatitis
- Being tested
- Isosorbide Dinitrate 5 MG, Indomethacin 100 MG, Sublingual Placebo, Rectal placebo
- Keywords
- ERCP, Post-ERCP pancreatitis, PEP, NSAIDs, indomethacin, nitrate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isosorbide Dinitrate 5 MGDrug
All patients without contraindications should receive sublingual isosorbide dinitrate tablet within 5 minutes before ERCP.
Indomethacin 100 MGDrug
All patients without contraindications should receive rectal indomethacin within 30 min before ERCP.
Sublingual PlaceboDrug
All patients without contraindications should receive sublingual placebo within 5 minutes before ERCP.
Rectal placeboDrug
All patients without contraindications should receive rectal placebo within 30 min before ERCP.
| Study group | Role | What they receive |
|---|---|---|
| Rectal indomethacin and sublingual nitrate | Experimental | All patients without contraindications should receive sublingual isosorbide dinitrate within 5 min before ERCP.
All patients without contraindications should receive rectal indomethacin within 30 min before ERCP. Receives: Drug: Isosorbide Dinitrate 5 MG; Drug: Indomethacin 100 MG |
| Rectal indomethacin and sublingual placebo | Active comparator | All patients without contraindications should receive sublingual placebo within 5 min before ERCP.
All patients without contraindications should receive rectal indomethacin within 30 min before ERCP. Receives: Drug: Indomethacin 100 MG; Drug: Sublingual Placebo |
| Rectal placebo and sublingual nitrate | Active comparator | All patients without contraindications should receive sublingual isosorbide dinitrate within 5 min before ERCP.
All patients without contraindications should receive rectal placebo within 30 min before ERCP. Receives: Drug: Isosorbide Dinitrate 5 MG; Drug: Rectal placebo |
| Rectal placebo and sublingual placebo | Placebo comparator | All patients without contraindications should receive sublingual placebo within 5 min before ERCP.
All patients without contraindications should receive rectal placebo within 30 min before ERCP. Receives: Drug: Sublingual Placebo; Drug: Rectal placebo |
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 PEP was established 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 the procedure, and hospitalization for at least 2 nights. Doctors are advised to use cross-sectional imaging to identify ambiguous PEP.
Measured: 14 days
Secondary outcomes (2)
Rate of moderate to severe PEP
The severity classification of pancreatitis was defined according to the criteria of Cotton et al and the revised Atlanta criteria.
Measured: 14 days
Other adverse events
Adverse effects of indomethacin, including gastrointestinal bleeding and renal failure.
Adverse effects of nitrates, including hypotension, headache and dizziness. Other post-ERCP adverse events including cholangitis, bleeding, and perforation.
Any other adverse outcomes possibly related to ERCP or experimental drugs that required hospital admission or a prolonged hospital stay for further management.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2020
- Study start1 Jul 2020
- Primary completion30 May 2022 (estimated)
- Study completion30 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)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
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,700 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
- NCT04425993
- Sponsor's protocol ID
- KY20200522-4
- Status last verified
- Oct 2020
- First submitted
- 8 Jun 2020
- Last updated
- 22 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Sotoudehmanesh R, Eloubeidi MA, Asgari AA, Farsinejad M, Khatibian M. A randomized trial of rectal indomethacin and sublingual nitrates to prevent post-ERCP pancreatitis. Am J Gastroenterol. 2014 Jun;109(6):903-9. doi: 10.1038/ajg.2014.9. Epub 2014 Feb 11.
PubMed 24513806Tomoda T, Kato H, Ueki T, Akimoto Y, Hata H, Fujii M, Harada R, Ogawa T, Wato M, Takatani M, Matsubara M, Kawai Y, Okada H. Combination of Diclofenac and Sublingual Nitrates Is Superior to Diclofenac Alone in Preventing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography. Gastroenterology. 2019 May;156(6):1753-1760.e1. doi: 10.1053/j.gastro.2019.01.267. Epub 2019 Feb 14.
PubMed 30772342Ding J, Jin X, Pan Y, Liu S, Li Y. Glyceryl trinitrate for prevention of post-ERCP pancreatitis and improve the rate of cannulation: a meta-analysis of prospective, randomized, controlled trials. PLoS One. 2013 Oct 1;8(10):e75645. doi: 10.1371/journal.pone.0075645. eCollection 2013.
PubMed 24098392Luo 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 27133971Luo H, Wang X, Zhang R, Liang S, Kang X, Zhang X, Lou Q, Xiong K, Yang J, Si L, Liu W, Liu Y, Zhou Y, Wang S, Yang M, Chen W, Han Y, Shang G, Yang X, He Y, Zou Q, Guo W, Dai Y, Zeng W, Zhu X, Gong R, Li X, Nie Z, Wang Q, Wang L, Pan Y, Guo X, Fan D. Rectal Indomethacin and Spraying of Duodenal Papilla With Epinephrine Increases Risk of Pancreatitis Following Endoscopic Retrograde Cholangiopancreatography. Clin Gastroenterol Hepatol. 2019 Jul;17(8):1597-1606.e5. doi: 10.1016/j.cgh.2018.10.043. Epub 2018 Oct 31.
PubMed 30391434
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rectal Indomethacin Versus Rectal Indomethacin and Sublingual Nitrate to Prevent Post-ERCP Pancreatitis: a Multicentre, Non-inferiority, Double-blind, Randomised Trial
- ClinicalTrials.gov ID
- NCT04425993
- Acronym / sponsor ID
- KY20200522-4
- Conditions
- Post-ERCP Acute Pancreatitis
- Keywords
- ERCP, Post-ERCP pancreatitis, PEP, NSAIDs, indomethacin, nitrate
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,700 participants (actual)
- Lead sponsor
- Air Force Military Medical University, ChinaUniversity, hospital or other
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- 30 May 2022 (estimated)
- Study completion
- 30 Dec 2022 (estimated)
- First posted
- 11 Jun 2020 (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.
Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) are at risk for post-ERCP pancreatitis (PEP), which is associated with adverse outcomes. Combination prophylaxis strategies are increasingly investigated to prevent PEP more effectively, and studies have confirmed the benefits. Two randomized controlled trials revealed that combination prophylaxis with rectal NSAIDs and sublingual nitrate has reduced PEP rates to 5.6%-6.7% in average-risk patients. However, there was concern regarding the safety of sublingual nitrate with reports of significant increasing the risk of hypotesion (rate of 54.9%) and headache (rate of 4.1%) as compared with placebo.
As a safety drug, rectal administration of one dose NSAIDs is recommended as basic chemoprophylaxis in common or high-risk patients in guidelines. Results from previous studies showed rectal administration of NSAIDs significantly reduced PEP rate to 4-5.3% in average-risk patients. Although the difference in demographics, study design and outcomes definition, evidence was obtained that rectal NSAIDS was associated with similar PEP rate as combination prophylaxis with rectal NSAIDs and sublingual nitrate. However, evidence is lacking from large, randomized clinical trials indicating that efficiency of PEP prevention with rectal NSAIDs alone is not inferior to with combination prophylaxis. The investigators conduct this trial to investigate the hypothesis that rectal NSAIDs alone is non-inferior to the combination prophylaxis in terms of PEP prevention, but with reduce side effect.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Rectal indomethacin and sublingual nitrate | Experimental | Drug: Isosorbide Dinitrate 5 MG, Drug: Indomethacin 100 MGAll patients without contraindications should receive sublingual isosorbide dinitrate within 5 min before ERCP. All patients without contraindications should receive rectal indomethacin within 30 min before ERCP. |
| Rectal indomethacin and sublingual placebo | Active comparator | Drug: Indomethacin 100 MG, Drug: Sublingual PlaceboAll patients without contraindications should receive sublingual placebo within 5 min before ERCP. All patients without contraindications should receive rectal indomethacin within 30 min before ERCP. |
| Rectal placebo and sublingual nitrate | Active comparator | Drug: Isosorbide Dinitrate 5 MG, Drug: Rectal placeboAll patients without contraindications should receive sublingual isosorbide dinitrate within 5 min before ERCP. All patients without contraindications should receive rectal placebo within 30 min before ERCP. |
| Rectal placebo and sublingual placebo | Placebo comparator | Drug: Sublingual Placebo, Drug: Rectal placeboAll patients without contraindications should receive sublingual placebo within 5 min before ERCP. All patients without contraindications should receive rectal placebo within 30 min before ERCP. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients (age, 18-80 y) with native papilla planned for diagnostic or therapeutic ERCP were eligible for enrollment in the study.
Key exclusion criteria (8 listed)
- contraindications to ERCP;
- allergy to nitrates or NSAIDs;
- currently on nitrate medication;
- receiving NSAIDs within 7 days;
- not suitable for indomethacin eg, gastrointestinal hemorrhage within the past 4 weeks, renal dysfunction (creatinine level >1.4 mg/dL) or the presence of coagulopathy before the procedure (international normalized ratio > 1.5);
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 |
|---|---|---|
| Isosorbide Dinitrate 5 MGAll patients without contraindications should receive sublingual isosorbide dinitrate tablet within 5 minutes before ERCP. | Drug | Rectal indomethacin and sublingual nitrate, Rectal placebo and sublingual nitrate |
| Indomethacin 100 MGAll patients without contraindications should receive rectal indomethacin within 30 min before ERCP. | Drug | Rectal indomethacin and sublingual nitrate, Rectal indomethacin and sublingual placebo |
| Sublingual PlaceboAll patients without contraindications should receive sublingual placebo within 5 minutes before ERCP. | Drug | Rectal indomethacin and sublingual placebo, Rectal placebo and sublingual placebo |
| Rectal placeboAll patients without contraindications should receive rectal placebo within 30 min before ERCP. | Drug | Rectal placebo and sublingual nitrate, Rectal placebo and sublingual placebo |
Primary outcome
Rate of post-ERCP Pancreatitis
Time frame: 14 days
The diagnosis of PEP was established 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 the procedure, and hospitalization for at least 2 nights. Doctors are advised to use cross-sectional imaging to identify ambiguous PEP.
2 secondary outcomes
Rate of moderate to severe PEP
Time frame: 14 days
Other adverse events
Time frame: 14 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2020.
- Background: PubMed 24513806Sotoudehmanesh R, Eloubeidi MA, Asgari AA, Farsinejad M, Khatibian M. A randomized trial of rectal indomethacin and sublingual nitrates to prevent post-ERCP pancreatitis. Am J Gastroenterol. 2014 Jun;109(6):903-9. doi: 10.1038/ajg.2014.9. Epub 2014 Feb 11.
- Background: PubMed 30772342Tomoda T, Kato H, Ueki T, Akimoto Y, Hata H, Fujii M, Harada R, Ogawa T, Wato M, Takatani M, Matsubara M, Kawai Y, Okada H. Combination of Diclofenac and Sublingual Nitrates Is Superior to Diclofenac Alone in Preventing Pancreatitis After Endoscopic Retrograde Cholangiopancreatography. Gastroenterology. 2019 May;156(6):1753-1760.e1. doi: 10.1053/j.gastro.2019.01.267. Epub 2019 Feb 14.
- Background: PubMed 24098392Ding J, Jin X, Pan Y, Liu S, Li Y. Glyceryl trinitrate for prevention of post-ERCP pancreatitis and improve the rate of cannulation: a meta-analysis of prospective, randomized, controlled trials. PLoS One. 2013 Oct 1;8(10):e75645. doi: 10.1371/journal.pone.0075645. eCollection 2013.
- Background: 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.
- Background: PubMed 30391434Luo H, Wang X, Zhang R, Liang S, Kang X, Zhang X, Lou Q, Xiong K, Yang J, Si L, Liu W, Liu Y, Zhou Y, Wang S, Yang M, Chen W, Han Y, Shang G, Yang X, He Y, Zou Q, Guo W, Dai Y, Zeng W, Zhu X, Gong R, Li X, Nie Z, Wang Q, Wang L, Pan Y, Guo X, Fan D. Rectal Indomethacin and Spraying of Duodenal Papilla With Epinephrine Increases Risk of Pancreatitis Following Endoscopic Retrograde Cholangiopancreatography. Clin Gastroenterol Hepatol. 2019 Jul;17(8):1597-1606.e5. doi: 10.1016/j.cgh.2018.10.043. Epub 2018 Oct 31.
- 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.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Isosorbide Dinitrate 5 MG and Indomethacin 100 MG in people with Post-ERCP Acute Pancreatitis, run by Air Force Military Medical University, China at 4 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: status not confirmed, as of the sponsor's last update on 22 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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. Some participants in this study may receive a placebo. 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?
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: 14 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 NCT04425993, which also lists 5 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 22 Oct 2020.