Post ERCP Acute Pancreatitis Clinical Trial
Official title:
Rectal Indomethacin Decreases the Incidence of Pancreatitis Following Endoscopic Retrograde Cholangiopancreatography in High-risk Patients
Endoscopic retrograde cholangiopancreatography (ERCP) is now a widely accepted therapy for treating benign and malignant diseases of the pancreatobiliary tree. Acute pancreatitis represents the most common and feared complication following ERCP. The reported incidence of this complication is from 1% to 40% according to the presence of high-risk factors for this complication or the presence dysfunction in the sphincter of Oddi (SOD). In most prospective series, the incidence has ranged between 3.5% and 20% for nonselected and high-risk patients, respectively. Independent risk factors for post-ERCP pancreatitis are either patient- or procedure-related.
Design This is a randomized clinical trial carried out in patients scheduled for ERCP at the
Department of Gastrointestinal Endoscopy and Department of Gastroenterology of the
Specialties Hospital of the Western Medical Center, in Guadalajara, Jalisco, Mexico. The
investigators include patients with an elevated baseline risk of post-ERCP pancreatitis
based on prospectively validated patient- and procedure-related independent risk factors.
The ERCP procedures are performed with the patient under topical pharyngeal anesthesia with
2% lidocaine and after administration of sedation (midazolam) and analgesia (fentanyl)
intravenously, with dosages at the discretion of the endoscopist. Patients receive
complementary oxygen through an external nasal device at 3 to 5 L/min and infusion of 200 to
500 mL of 0.9% sterile saline solution.
The equipment and protocol that are being used to perform ERCP consist of a video
duodenoscope (Olympus, Tokyo, Japan), sphincterotome traction for selective cannulation of
the bile duct, a needle scalpel to perform precut sphincterotomy, a hydrophilic guide wire
via the bile duct, a Dormia basket and/or balloon catheter for stone extraction, and
nonionic water-soluble contrast medium at 300 mg/mL (Optira 300™; ioversol injection 64%;
Mallinckrodt Pharmaceuticals, Dublin, Ireland) for opacification of the biliary and
pancreatic ducts.
Pancreatic stents are being used only to treat pancreatic fistulas and to prevent
pancreatitis. All patients are monitored continuously during the procedure, with
determinations of blood pressure, heart rate, respiratory rate, and arterial blood oxygen
saturation.
Eligible patients who provide written informed consent undergo the randomization at
conclusion of the ERCP procedure because patients without risk factors could be included in
the study based on procedure-related factors alone. If patients met the inclusion criteria,
they are randomly assigned to receive a 100 mg suppository of indomethacin or 2.4 g of
glycerin suppository immediately afterwards while still under sedation. All patients are
observed to prevent spontaneous expulsion of the suppository until they became completely
awake. All patients, staff endoscopists, residents, and researchers are blinded to the
treatment assigned to each of them.
The following data that is being collected.
1. A clinical history, particularly patient-related risk factors for post-ERCP
pancreatitis; blood test results for the determination of basal amylase, liver enzymes,
and bilirubin levels; as well as results of ultrasonography of the liver and biliary
tract.
2. All data generated during the ERCP is being recorded, particularly those related to
procedure-related risk factors for developing acute pancreatitis. In addition, other
nonpancreas-related complications are being recorded as perforation or bleeding.
3. Any adverse events related to the rectally applied indomethacin or glycerin
suppositories are being recorded as expulsion, irritation, or bleeding.
Post-ERCP pancreatitis is considered the main outcome variable and is defined as the
development of new or increased abdominal pain consistent with pancreatitis, and elevated
blood amylase or lipase >3 times the upper limit of normal until 24 h after the procedure,
and hospitalization (or prolongation of existing hospitalization) for at least 2 nights. The
severity is determined according to consensus guidelines, with mild post-ERCP pancreatitis
resulting in hospitalization of less than 3 days, and moderate post-ERCP pancreatitis
resulting in hospitalization of 4-10 days. Severe post-ERCP pancreatitis is qualified as
resulting in a hospitalization of >10 days, or leading to the development of pancreatic
necrosis or pseudocysts, or requiring percutaneous or surgical intervention. Patients with
acute pancreatitis are being followed up for 30 days after hospital discharge. Asymptomatic
hyperamylasemia is defined as any amylase level at least three times above the normal serum
level in the absence of abdominal pain.
Follow up The patients are kept under surveillance in the endoscopy recovery area for 3 h
after ERCP. Measurement of serum amylase is determined at 2 h post-ERCP in all included
patients. Asymptomatic outpatients are discharged after 6 h of surveillance with monitoring
for signs and symptoms of acute post-ERCP pancreatitis by telephone contact for 24 hours.
Hospitalized asymptomatic patients are being discharged to their assigned bed after 4 hours
of surveillance, where clinical surveillance is continued for up to 24 h. If new abdominal
pain suggestive of pancreatic origin appeares at any time, the 2-h amylase level is checked
and confirmed with serum lipase determination.
All routine laboratory examinations are being performed when acute pancreatitis of any
etiology is established. All patients diagnosed with post-ERCP pancreatitis are being
managed under the medical care of the Department of Gastroenterology.
Patients are being submitted to computed tomography scanning to determine the severity of
the episode of pancreatitis. Severity was established according to Cotton's criteria.
Statistical analysis Statistical software, SPSS for IBM (version 20 for Windows; IBM Corp.,
Armonk, NY, USA) is beign used for data analysis.
The data obtained will be expressed as frequencies and percentages, means and standard
deviations. For comparing results, Student's t test will be used for continuous variables
and Chi2 or Fisher's exact tests will be used for qualitative data when appropriate.
Relative risk (RR) and 95% confidence intervals (95% CI) will be determined as well as the
absolute risk reduction (ARR), relative risk reduction (RRR), and number needed to treat
(NNT).
Statistical significance from two-tailed tests was assumed when p < 0.05
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment