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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Isosorbide Dinitrate 5 MG | Drug | All patients without contraindications should receive sublingual isosorbide dinitrate tablet within 5 minutes before ERCP. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 14 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 14 days |
| Other adverse events |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Xiamen Humanity Hospital | Xiamen | Fujian | China | |||
| Lanzhou University Second Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24513806 | Background | 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. | |
| 30772342 | Background | Tomoda 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. |
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| ID | Term |
|---|---|
| D007548 | Isosorbide Dinitrate |
| D007213 | Indomethacin |
| ID | Term |
|---|---|
| D007547 | Isosorbide |
| D013012 | Sorbitol |
| D013402 | Sugar Alcohols |
| D000438 | Alcohols |
| D009930 |
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| Indomethacin 100 MG | Drug | All patients without contraindications should receive rectal indomethacin within 30 min before ERCP. |
|
| Sublingual Placebo | Drug | All patients without contraindications should receive sublingual placebo within 5 minutes before ERCP. |
|
| Rectal placebo | Drug | All patients without contraindications should receive rectal placebo within 30 min before ERCP. |
|
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.
| 14 days |
| Lanzhou |
| Gansu |
| 730030 |
| China |
| Xi'an Central Hospital | Xi'an | Shaanxi | 710032 | China |
| Xijing Hoapital | Xi'an | Shaanxi | 710032 | China |
| 24098392 | Background | Ding 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. |
| 27133971 | 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. |
| 30391434 | Background | Luo 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. |
| Organic Chemicals |
| D002241 | Carbohydrates |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |