Randomized Trial of Rectal Indomethacin and Papillary Spray of Epinephrine Versus Rectal Indomethacin to Prevent Post-ERCP Pancreatitis

NCT02116309 | Completed Results DMC

• 1 other identifier: IRB00034715
• Study Type: interventional
• Target: 948
• Locations: 2 countries
• Sites: 4

Brief Summary

This research is being done to see if using a combination of rectal indomethacin and epinephrine spray during endoscopy, can prevent pancreatitis that may occur after ERCP (a type of gastrointestinal endoscopy).

Conditions

Post-ERCP Acute Pancreatitis

Outcome Measures

Primary Outcomes (1)

• Number of Patients Who Developed Post-ERCP Pancreatitis

  The primary outcome variable of interest is the incidence of post ERCP pancreatitis (PEP) as defined by the consensus guidelines as 1) New or increased abdominal pain that is clinically consistent with a syndrome of acute pancreatitis and 2) amylase or lipase ≥ 3x the upper limit of normal 24 hours after the procedure and 3) Hospitalization or prolongation of existing hospitalization for at least 2 days.

  24 hours after ERCP

Secondary Outcomes (1)

• Number of Patients Who Developed Severe Post-ERCP Pancreatitis

  up to 30 days after ERCP

Study Arms (2)

Rectal Indomethacin only

ACTIVE COMPARATOR

Patients in this group will receive 20 ml of normal saline sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin.

Drug: Rectal Indomethacin

Rectal Indomethacin plus papillary spray of Epinephrine

ACTIVE COMPARATOR

Patients in this group will receive 20 ml of 0.02% epinephrine sprayed on the duodenal papilla and surrounding regions of edema, over a period of 1 minute using any ERCP cannulation catheter, at the end of procedure, just before the withdrawal of endoscope; followed by 100 mg of rectal indomethacin.

Drug: Rectal Indomethacin; Drug: Epinephrine

Interventions

Rectal Indomethacin DRUG

Also known as: Indocin, NSAIDs

Rectal Indomethacin only; Rectal Indomethacin plus papillary spray of Epinephrine

Epinephrine DRUG

Also known as: Adrenaline

Rectal Indomethacin plus papillary spray of Epinephrine

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• History of PEP
• Pancreatic sphincterotomy
• Pre-cut sphincterotomy
• Difficult cannulation (\>5 attempts / 10 minutes to cannulate)
• Failed cannulation
• Pneumatic dilation of an intact sphincter
• Sphincter of Oddi dysfunction of Type I or Type II
• Age \< 50 \& Female gender
• History of acute pancreatitis (at least 2 episodes)
• \>/= 3 pancreatic injections (with at least 1 injection in tail)
• Pancreatic acinarization
• Pancreatic Brush Cytology

You may not qualify if:

• Unwillingness or inability to consent for the study
• Age \< 18 years
• Intrauterine pregnancy
• Breastfeeding mother
• Standard contraindications to ERCP
• Allergy / hypersensitivity to aspirin or NSAIDs or epinephrine
• Chronic renal disease (Cr \> 1.4)
• Active or recent (within 4 weeks) gastrointestinal hemorrhage
• Acute pancreatitis (lipase peak) within 72 hours
• Known chronic calcific pancreatitis
• Pancreatic head mass
• Receiving pancreatic duct stent placement for any indication
• Procedure performed on major papilla/ventral pancreatic duct in patients with pancreas divisum
• ERCP for pancreatic/biliary stent removal or exchange without anticipated pancreatogram
• Subject with prior biliary sphincterotomy now scheduled for repeat biliary therapy without anticipated pancreatogram

Sponsors & Collaborators

• Johns Hopkins University: lead
• American Society for Gastrointestinal Endoscopy: collaborator
• Asian Institute of Gastroenterology, India: collaborator
• Post Graduate Institute of Medical Education and Research, Chandigarh: collaborator
• Apollo Gleneagles Hospitals, Kolkata: collaborator

Study Sites (4)

Johns Hopkins Medical Institutions

Baltimore, Maryland, 21287, United States

Location

Asian Institute of gastroenterology

Hyderabad, Andhra Pradesh, 500082, India

Location

Apollo Gleneagles Hospitals

Kolkata, West Bengal, 700054, India

Location

Post Graduate Institute of Medical Education and Research

Chandigarh, 160012, India

Location

Related Publications (5)

• 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.

  PMID: 22494121 BACKGROUND

• Akshintala VS, Hutfless SM, Colantuoni E, Kim KJ, Khashab MA, Li T, Elmunzer BJ, Puhan MA, Sinha A, Kamal A, Lennon AM, Okolo PI, Palakurthy MK, Kalloo AN, Singh VK. Systematic review with network meta-analysis: pharmacological prophylaxis against post-ERCP pancreatitis. Aliment Pharmacol Ther. 2013 Dec;38(11-12):1325-37. doi: 10.1111/apt.12534. Epub 2013 Oct 20.

  PMID: 24138390 BACKGROUND

• Xu LH, Qian JB, Gu LG, Qiu JW, Ge ZM, Lu F, Wang YM, Li YM, Lu HS. Prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis by epinephrine sprayed on the papilla. J Gastroenterol Hepatol. 2011 Jul;26(7):1139-44. doi: 10.1111/j.1440-1746.2011.06718.x.

  PMID: 21392105 BACKGROUND

• Matsushita M, Takakuwa H, Shimeno N, Uchida K, Nishio A, Okazaki K. Epinephrine sprayed on the papilla for prevention of post-ERCP pancreatitis. J Gastroenterol. 2009;44(1):71-5. doi: 10.1007/s00535-008-2272-8. Epub 2009 Jan 22.

  PMID: 19159075 BACKGROUND

• Kamal A, Akshintala VS, Talukdar R, Goenka MK, Kochhar R, Lakhtakia S, Ramchandani MK, Sinha S, Goud R, Rai VK, Tandan M, Gupta R, Elmunzer BJ, Ngamruengphong S, Kumbhari V, Khashab MA, Kalloo AN, Reddy DN, Singh VK. A Randomized Trial of Topical Epinephrine and Rectal Indomethacin for Preventing Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in High-Risk Patients. Am J Gastroenterol. 2019 Feb;114(2):339-347. doi: 10.14309/ajg.0000000000000049.

  PMID: 30730860 DERIVED

MeSH Terms

Interventions

Indomethacin; Anti-Inflammatory Agents, Non-Steroidal; Epinephrine

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Anti-Inflammatory Agents; Therapeutic Uses; Antirheumatic Agents; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Dr. Vikesh Singh
• Organization: Johns Hopkins University

vakshin1@jhmi.edu

4106146708

Study Officials

• Vikesh K Singh, M.D., M.Sc.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2014
• First Posted: April 16, 2014
• Study Start: August 1, 2014
• Primary Completion: December 2, 2016
• Study Completion: December 2, 2016
• Last Updated: November 1, 2017
• Results First Posted: November 1, 2017

Record last verified: 2017-10

Locations

US (1); IN (3)