Diclofenac for the Prevention of Post-ERCP Pancreatitis in Higher Risk Patients
Diclofenac for the Prevention of Post-ERCP Pancreatitis in Higher Risk Patients
Inflammation of the pancreas (pancreatitis) is an uncommon but potentially serious
 complication of endoscopic retrograde cholangiopancreatography (ERCP), a specialized
 endoscopic examination of the ducts draining the liver and pancreas. Although many different
 strategies have been tried and studied in attempts to reduce this risk, few have been shown
 to make a significant difference. Those that have are either very expensive, difficult to
 administer, or both.

 Diclofenac, an anti-inflammatory medication most often used to treat arthritis, has shown
 potential to decrease the risk of post-ERCP pancreatitis. It can be given after the procedure
 to patients at most risk for the complication, and has few side effects. This study will
 randomize people in the study to placebo or active medication, to determine if Diclofenac
 reduces the incidence of pancreatitis.
Hypothesis:

 Diclofenac, when administered immediately post ERCP in patients at higher risk of developing
 post-ERCP pancreatitis, will significantly reduce the incidence of this complication.

 Intervention:

 All patients undergoing ERCP not having exclusion criteria will be approached for
 participation prior to the procedure. At the end of the procedure, prior to transfer from the
 endoscopy suite, within 15 minutes of the end of the procedure, if the patient meets
 inclusion criteria, a study suppository will be administered.

 The suppositories will be prepared by a study pharmacist according to a randomization list
 prepared by an independent biostatistician. They will be randomized using a permuted block
 design, in blocks of 20. The placebo is inert, and identical to the study medication, a 100
 mg diclofenac rectal suppository. The code will not be broken until enrolment of patients is
 complete.

 Patients, endoscopists, nurses, and the principal investigator will all be blinded to the
 randomization code.

 Outcomes:

 Post-ERCP acute pancreatitis is the primary outcome. Consensus definition of this is new
 typical (epigastric/retroperitoneal) pain combined with an elevation of serum lipase or
 amylase >3 times the upper limit of normal. Pain will be assessed through history and
 physical exam by an attending gastroenterologist the morning after the procedure, with
 documentation in the chart and research form of the presence or absence of pain. Serum
 amylase will be measured the morning after the procedure, between 7 and 10 am (approximately
 18 hours post procedure). Most patients will be inpatients but outpatients will be included
 if they can be assessed through clinical exam and blood chemistry analysis the following
 morning. Patients will be contacted one week after the procedure to ensure no episode of
 abdominal pain or bleeding has been missed.

 Statistics and Power Calculation

 A two sided Fisher's Exact Test will be used to compare the proportion of patients developing
 post-ERCP pancreatitis in each group (placebo vs. active drug).

 In the population selected, the estimated risk of pancreatitis is 15%. To demonstrate a
 decrease to 5%, 141 patients will be required in each group, with 80% power and an alpha
 error 0.05. Secondary outcomes will include severity of pancreatitis, hyperamylasemia, length
 of stay, and mortality. Safety data regarding renal function and GI bleeding will also be
 collected.
Inclusion Criteria:

 These were chosen based on a review of the major studies evaluating risk factors for
 post-ERCP pancreatitis. Any of the following factors placing a patient at high risk (>10%)
 of post ERCP pancreatitis:

 -  Patient characteristics: Prior history of post-ERCP pancreatitis, prior history of
 acute pancreatitis, suspected Sphincter of Oddi dysfunction, or normal bilirubin;

 -  Procedure related factors: Moderate (6-15 attempts) and difficult (>15 attempts) bile
 duct cannulation, balloon dilation of the biliary sphincter, pre-cut papillotomy,
 pancreatic sphincterotomy.

 Exclusion Criteria:

 -  Ongoing acute or chronic pancreatitis;

 -  Previous biliary sphincterotomy;

 -  Contra-indications to non-steroidal anti-inflammatory medications (allergy, reduced
 renal function, recent upper gastrointestinal bleeding);

 -  Ingestion of an NSAID ( nonsteroidal anti-inflammatory drug) in the previous 7 days.