Topical Pancreatic Duct Lidocaine for Prevention of Post-ERCP Pancreatitis

• ClinicalTrials.gov Identifier: NCT00953199
• Recruitment Status: Completed
• First Posted: August 6, 2009
• Results First Posted: October 3, 2017
• Last Update Posted: October 3, 2017
• Sponsor: Abraham Mathew MD
• Collaborator: Milton S. Hershey Medical Center
• Information provided by (Responsible Party): Abraham Mathew MD, Milton S. Hershey Medical Center

Study Description

Brief Summary:

The purpose of this study is to determine if lidocaine is effective in reducing the incidence of post-ERCP pancreatitis.

Condition or disease	Intervention/treatment	Phase
Pancreatitis	Drug: Lidocaine Hydrochloride; Drug: Normal Saline	Not Applicable

Detailed Description:

Post endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is a common cause of morbidity for which there is no known pharmacologic prophylaxis. Post-ERCP pancreatitis is thought to be caused by several factors, including intraductal pressure, multiple duct injections with contrast, and neural arc reflexes. Lidocaine is a safe, inexpensive class IV antiarrhythmic that has topical anesthetic effects, inhibits trypsin activity, and may potentially prevent post-ERCP pancreatitis by injection directly into the pancreatic duct at the time of ERCP. Lidocaine has been shown to inhibit phospholipase A2, a key pancreatic enzyme, interrupt local arc reflexes to stop neuronal transmission, and to dampen GI tract mucosal reflexes to prevent high ductal pressure.

The key objective of this study is to determine if injection of lidocaine is beneficial in preventing post-ERCP pancreatitis. Subjects will be randomized to study group or control group in an equal ratio. The physicians performing the ERCP will be unaware of the treatment group to which patients have been assigned. Study arm will receive contrast agent Diatrizoate 60% (5 ml) diluted with lidocaine 2% (5 ml) during ERCP. Control arm will receive contrast agent Diatrizoate 60% (5 ml) diluted with normal saline 0.9% (5 ml) during ERCP. Diatrizoate diluted with normal saline is the standard of care. Patients will be contacted 1 day and 1 week post-ERCP to assess for symptoms of pancreatitis.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 506 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Single Center, Randomized, Double-Blind Controlled Study of Topical Endoluminal Pancreatic Duct Lidocaine for Prevention of Post-ERCP Pancreatitis
• Study Start Date: March 2010
• Actual Primary Completion Date: May 2013
• Actual Study Completion Date: May 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: Lidocaine; Study subjects receive a 1:1 combination of 5 ml Diatrizoate 60% and 5 ml Lidocaine Hydrochloride 2%	Drug: Lidocaine Hydrochloride; 1:1 combination of contrast dye Diatrizoate 60% (5 ml) diluted with lidocaine 2% (5 ml) used at ERCP. Lidocaine will only be used once, and thus a maximum dose of 100 mg will be employed. If the patient requires more contrast agent, this will be used without the addition of lidocaine.
Active Comparator: Normal Saline; The control arm receives a 1:1 combination of 5 ml Diatrizoate and 5ml saline.	Drug: Normal Saline; 1:1 combination of contrast dye Diatrizoate 60% (5 ml) diluted with normal saline 0.9% (5 ml) used at ERCP (standard of care).

Outcome Measures

Primary Outcome Measures :

1. Post ERCP Pancreatitis is the Primary Outcome. [ Time Frame: 24-48 hours post-procedure ]
   The primary outcome of interest will be development of acute pancreatitis defined as new or worsening abdominal pain post-ERCP associated with an increase in serum amylase at least 3 times the upper limit of normal.

Secondary Outcome Measures :

1. Serum Amylase Levels [ Time Frame: measurement is taken 2 hrs after ERCP ]
   serum amylase levels are measure by a blood draw

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients included are >18 years old, referred to Endoscopy Clinic for an ERCP for any well established indication such as: biliary strictures, benign and malignant hepato-pancreato-biliary tumors, chronic pancreatitis, and suspected sphincter of Oddi dysfunction

Exclusion Criteria:

• Known sensitivity to lidocaine or contrast agent
• History of seizure disorder
• History of cardiac arrhythmia (tachyarrhythmia, bradyarrhythmia, cardiac conduction defects, prolonged QT syndrome)
• History of congestive heart failure
• Active acute pancreatitis before procedure
• Planned biliary stent removal without pancreatogram
• Pregnancy
• Incarcerated individuals
• Less than 18 years of age
• Previous sphincterotomy
• Inability to give informed consent

Contacts and Locations

Locations

United States, Pennsylvania

Penn State College of Medicine, Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States, 17033

Sponsors and Collaborators

Abraham Mathew MD

Milton S. Hershey Medical Center

Investigators

• Principal Investigator: Abraham Mathew, M.D., M.S.; Milton S. Hershey Medical Center

More Information

Publications:

Cosen-Binker LI, Binker MG, Negri G, Tiscornia O. Acute pancreatitis possible initial triggering mechanism and prophylaxis. Pancreatology. 2003;3(6):445-56. doi: 10.1159/000074972. Epub 2003 Nov 19.

Kiyonari Y, Nishina K, Mikawa K, Maekawa N, Obara H. Lidocaine attenuates acute lung injury induced by a combination of phospholipase A2 and trypsin. Crit Care Med. 2000 Feb;28(2):484-9. doi: 10.1097/00003246-200002000-00033.

Makela A, Kuusi T, Schroder T. Inhibition of serum phospholipase-A2 in acute pancreatitis by pharmacological agents in vitro. Scand J Clin Lab Invest. 1997 Aug;57(5):401-7. doi: 10.3109/00365519709084587.

Portiansky EL, Gonzalez PH. Protective effect of lidocaine in the experimental foot-and-mouth disease pancreatitis. Experientia. 1995 Nov 15;51(11):1060-2. doi: 10.1007/BF01946916.

Schroder T, Kinnunen PK, Lempinen M. Xylocaine treatment in experimental pancreatitis in pigs. Scand J Gastroenterol. 1978;13(7):863-5. doi: 10.3109/00365527809182204.

Schwartz JJ, Lew RJ, Ahmad NA, Shah JN, Ginsberg GG, Kochman ML, Brensinger CM, Long WB. The effect of lidocaine sprayed on the major duodenal papilla on the frequency of post-ERCP pancreatitis. Gastrointest Endosc. 2004 Feb;59(2):179-84. doi: 10.1016/s0016-5107(03)02540-9.

• Responsible Party: Abraham Mathew MD, Professor of Medicine, Milton S. Hershey Medical Center
• ClinicalTrials.gov Identifier: NCT00953199
• Other Study ID Numbers: Lidocaine
• First Posted: August 6, 2009
• Results First Posted: October 3, 2017
• Last Update Posted: October 3, 2017
• Last Verified: September 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Abraham Mathew MD, Milton S. Hershey Medical Center:

endoscopic retrograde cholangiopancreatography; ERCP; pancreatitis; lidocaine; post-ERCP pancreatitis

Additional relevant MeSH terms:

Pancreatitis; Pancreatic Diseases; Digestive System Diseases; Lidocaine; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents; Anti-Arrhythmia Agents; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action