Topical Pancreatic Duct Lidocaine for Prevention of Post-ERCP Pancreatitis

• Sponsor: Abraham Mathew MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT00953199
• Collaborator: Milton S. Hershey Medical Center (Other)
• Enrollment: 506
• Location: 1
• Arms: 2
• Duration (Months): 38
• Patients Per Site Per Month: 13.3

Study Details

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	N/A

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
• 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: Mar 1, 2010
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 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. [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 [measurement is taken 2 hrs after ERCP]

   serum amylase levels are measure by a blood draw

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

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. 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.
• Mäkelä A, Kuusi T, Schröder 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.
• Portiansky EL, González PH. Protective effect of lidocaine in the experimental foot-and-mouth disease pancreatitis. Experientia. 1995 Nov 15;51(11):1060-2.
• Schröder T, Kinnunen PK, Lempinen M. Xylocaine treatment in experimental pancreatitis in pigs. Scand J Gastroenterol. 1978;13(7):863-5.
• 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.

• Responsible Party: Abraham Mathew MD, Professor of Medicine, Milton S. Hershey Medical Center
• ClinicalTrials.gov Identifier: NCT00953199
• Other Study ID Numbers: Lidocaine
• First Posted: Aug 6, 2009
• Last Update Posted: Oct 3, 2017
• Last Verified: Sep 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Abraham Mathew MD, Professor of Medicine, Milton S. Hershey Medical Center: endoscopic retrograde cholangiopancreatography; ERCP; pancreatitis; lidocaine; post-ERCP pancreatitis
• Additional relevant MeSH terms: Pancreatitis; Lidocaine

Study Results

Participant Flow

Recruitment Details	March 2010 -May 2013, recruited from the endoscopy unit

Arm/Group Title	Lidocaine	Normal Saline
Arm/Group Description	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.	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).
Period Title: Overall Study
STARTED	254	252
COMPLETED	254	252
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Lidocaine	Normal Saline	Total
Arm/Group Description	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.	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).	Total of all reporting groups
Overall Participants	254	252	506
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	56	55.6	55.8
Sex: Female, Male (Count of Participants)
Female	128 50.4%	126 50%	254 50.2%
Male	126 49.6%	126 50%	252 49.8%

Outcome Measures

1. Primary Outcome

Title	Post ERCP Pancreatitis is the Primary Outcome.
Description	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.
Time Frame	24-48 hours post-procedure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lidocaine	Normal Saline
Arm/Group Description	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.	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).
Measure Participants	254	252
Number [participants]	26 10.2%	20 7.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lidocaine, Normal Saline
	Comments	We calculated the sample size to be 570 in each arm, providing 80% power, allocation 1:1, two-sided, alpha 0.05, withdrawal rate of 3% and a reduction in pancreatitis from 8% to 4%. Randomization is performed with permuted blocks of 20. Analysis is based on intention to treat.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.45
	Comments	.05 was set as level of significance
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Serum Amylase Levels
Description	serum amylase levels are measure by a blood draw
Time Frame	measurement is taken 2 hrs after ERCP

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lidocaine	Normal Saline
Arm/Group Description	Study subjects receive a 1:1 combination of 5 ml Diatrizoate 60% and 5 ml Lidocaine Hydrochloride 2% 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.	The control arm receives a 1:1 combination of 5 ml Diatrizoate and 5ml saline. 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).
Measure Participants	254	252
Mean (Full Range) [units/liter]	130	128

Adverse Events

Time Frame	Adverse event data was collected over 48 hrs. Patients are observed in the recovery area until they are discharged after ERCP or admitted, usually about 2-3 hrs. They are called after 24 -48 hrs and later after a week for follow up.
Adverse Event Reporting Description	Pancreatitis and its symptoms were the study outcomes and not considered here as a separate adverse event
Arm/Group Title	Lidocaine		Normal Saline
Arm/Group Description	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.		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).
All Cause Mortality
	Lidocaine		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/254 (0%)		0/252 (0%)
Serious Adverse Events
	Lidocaine		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/254 (0%)		0/252 (0%)
Other (Not Including Serious) Adverse Events
	Lidocaine		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/254 (0%)		0/252 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.