Rectal Indomethacin to Prevent Post-ERCP Pancreatitis (Indomethacin)

Routine Rectal Indomethacin Given Before Procedure Reduced Overall Pancreatitis in Patients Undergoing Endoscopic Retrograde Cholangiopancreatography (ERCP): A Multi-center, Single-blinded, Randomized Controlled Trial

Acute pancreatitis is the most common and feared complication of ERCP, occurring after 1% to 30% of procedures. Since 2012, a multicenter RCT was published in NEJM, indomethacin use in high risk patients was considered a "standard" method to prevent PEP. However, the risk factors of PEP is not fully clear. Rectal indomethacin before ERCP for all patients, not just for selected high-risk patients, may preventing PEP maximum. The purpose of this study is to determine whether routine using of rectal indomethacin is more effective than the conditional strategy.

Study Overview

• Status: Completed
• Conditions: Post-ERCP Acute Pancreatitis
• Intervention / Treatment: Drug: Pre-ERCP rectal Indomethacin; Drug: Post-operational Rectal Indomethacin

• Study Type: Interventional
• Enrollment (Actual): 2600
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • The First Hospital of Lanzhou University
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • General Hospital of Ningxia Medical University
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University
    • Xi'an, Shaanxi, China, 710032
      • Xijing Hospital of Digestive Diseases
    • Xi'an, Shaanxi, China, 710054
      • No. 451 Hospital
  • Xinjiang
    • Urumqi, Xinjiang, China, 830002
      • Urumqi General Hospital of Lanzhou Military Region

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients undergoing diagnostic or therapeutic ERCP.

Exclusion Criteria:

• Unwillingness or inability to consent for the study;
• Age < 18 years old;
• Intrauterine pregnancy;
• Breastfeeding mother;
• Standard contraindications to ERCP;
• Allergy to NSAIDs;
• Received NSAIDs in prior 7 days;
• Renal failure (Cr >1.4mg/dl=120umol/l);
• Active or recurrent (within 4 weeks) gastrointestinal hemorrhage;
• Acute pancreatitis within 72 hours;
• Known pancreatic head mass;
• Subject with prior biliary sphincterotomy now scheduled for repeat biliary therapy without anticipated pancreatogram;
• ERCP for biliary stent removal or exchange without anticipated pancreatogram;
• Known active cardiovascular or cerebrovascular disease.
• Presence of coagulopathy before the procedure or received anticoagulation therapy within three days before the procedure;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pre-ERCP group; Pre-ERCP rectal Indomethacin in all patients.	Drug: Pre-ERCP rectal Indomethacin; Rectal Indomethacin was administrated within 30min before ERCP in all patients.
Active Comparator: Post-ERCP group; Post-ERCP rectal Indomethacin in high-risk patients.	Drug: Post-operational Rectal Indomethacin; Rectal Indomethacin was administrated immediately after ERCP in high-risk patients, while average risk patients did not.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-ERCP Pancreatitis	Subjects were diagnosed with post-ERCP pancreatitis if they experienced new upper abdominal pain, serum amylase elevation at least three times the upper limit of normal 24 hours after the procedure, and hospitalization prolonged at least two nights.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Moderate-to-severe Pancreatitis	Moderate pancreatitis requiring hospitalization of 4-10 days. Severe pancreatitis requiring hospitalization for more than 10 days, or hemorrhagic pancreatitis, phlegmon or pseudocyst, or intervention (percutaneous drainage or surgery).	30 days

Collaborators and Investigators

• Sponsor: Air Force Military Medical University, China
• Investigators: Study Director: Yanglin Pan, M.D., Xijing Hospital of Digestive Diseases.The Fourth Military Medical University

Publications and helpful links

General Publications

• Elmunzer BJ, Scheiman JM, Lehman GA, Chak A, Mosler P, Higgins PD, Hayward RA, Romagnuolo J, Elta GH, Sherman S, Waljee AK, Repaka A, Atkinson MR, Cote GA, Kwon RS, McHenry L, Piraka CR, Wamsteker EJ, Watkins JL, Korsnes SJ, Schmidt SE, Turner SM, Nicholson S, Fogel EL; U.S. Cooperative for Outcomes Research in Endoscopy (USCORE). A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med. 2012 Apr 12;366(15):1414-22. doi: 10.1056/NEJMoa1111103.
• Ding X, Chen M, Huang S, Zhang S, Zou X. Nonsteroidal anti-inflammatory drugs for prevention of post-ERCP pancreatitis: a meta-analysis. Gastrointest Endosc. 2012 Dec;76(6):1152-9. doi: 10.1016/j.gie.2012.08.021.
• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: December 1, 2013
• First Submitted That Met QC Criteria: December 1, 2013
• First Posted (Estimate): December 6, 2013

Study Record Updates

• Last Update Posted (Estimate): June 29, 2016
• Last Update Submitted That Met QC Criteria: May 27, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Indomethacin, pancreatitis, ERCP
• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Reproductive Control Agents; Gout Suppressants; Tocolytic Agents; Indomethacin
• Other Study ID Numbers: 20131106-7 (Other Identifier: Ethics committee of Xijing Hospital)