Pancreatitis is the most common and serious complication following post-endoscopic retrograde cholangiopancreatography (ERCP) and is associated with occasional mortality, extended hospital stays, and increased healthcare expenses. Rectal non-steroidal anti-inflammatory drugs (NSAIDs) and pancreatic duct stent (PDS) placement were demonstrated to be effective strategyies to reduce PEP incidences, particlularly in high-risk patients for post-ERCP pancreatitis (PEP).
Rectal NSAIDs were easy-to-use and safe, while PDS placement were technically complex and carried higher risks of adverse events. A previous network meta-analysis suggested rectal NSAIDs in combination with PDS placement did not differ from rectal NSAIDs alone in PEP prevention. To invesigate if rectal NSAIDs alone could obivate the need of PDS placement, a recent trial from Elmunzer et al. conducted a randomized trial to investigate if rectal NSAIDs alone was non-inferior to the combination of NSAIDs with PDS in high-risk patients. The trial found that the PEP incidence rate in combination group was significantly lower than that in NSAIDs alone group. However, post-hoc analysis of the study suggested that the combination strategy conferred significant benefits only in high-risk patients with pancreatic duct (PD) wire passage, but not in those with other risk factors. Therefore, we hypothesized that rectal NSAIDs alone may obivate the need of PDS in high-risk patients without PD wire passages. Here, we conducted a multicenter, randomized and non-inferiority trial to investigate whether rectal NSAIDs alone is non-inferior to NSAIDs plus PDS placement in high-risk patients without PD wire passages.
18-90 years old patients with native papilla who planned to undergo ERCP
high-risk patients for post-ERCP pancreatitis must meet one or more following criteria: clinical suspicion of sphincter of Oddi dysfunction, a history of PEP, pancreatic sphincterotomy, precut sphincterotomy, difficult cannulation (>5 cannulation attempts, or >5mins cannulation time, or >1 unintentional pancreatic duct cannulation), or ballon dilatation of an intact biliary sphincter ≤ 1 min, double-wire cannulation. Additionally, patients were considered high-risk if they fulfilled two or more of the following minor criteria: female gender under 50 years old, a history of recurrent pancreatitis (two or more episodes), three or more contrast injections into the pancreatic duct with at least one injection reaching the tail of the pancreas, opacification of pancreatic acini, or brush cytology performed on the pancreatic duct.
Previous biliary sphincterotomy and papillary large balloon dilation
Planned for placements of pancreatic duct stents (eg. pancreatic duct strictures, planned ampullectomy)
Allergy to NSAIDs
The administration of NSAIDs within 7 days
Parallel
NSAIDs
DrugAll patients without contraindications should receive 100mg rectal indomethacin or diclofenac within 30mins before ERCP procedure
NSAIDs plus PDS
DeviceAll patients without contraindications should receive 100mg rectal indomethacin or diclofenac within 30mins before ERCP procedure. When eligibility is met, PDS placement will be performed by ERCP colonoscopists.
Rate of post-ERCP Pancreatitis
a new or aggravated upper abdominal pain, with an elevated pancreatic enzyme of at least 3 times as the upper limit of normal value 24h after procedure and prolonged hospitalization days for at least 2 days. This definition was based on a widely recognized Cotton consensus
Rate of mild, moderate or severe PEP
The severity classification of post-ERCP pancreatitis was defined according to the Cotton Criteria. Mild PEP: with an extension of hospitalization period of 2-3 days; Moderate PEP: with an extension of hospitalization period of 4-10 days; Severe PEP: with an extension of more than 10 days, or hemorrhagic pancreatitis, phlegmon, or pseudocyst, intervention (percutaneous drainage or surgery), or death.
Rate of patients with different severity of pancreatitis evaluated by revised Atlanta criteria
Mild: The most common form of acute pancreatitis, without organ failure or local or systemic complications, generally resolving within 1 week of onset. Moderately Severe: the presence of transient organ failure, local complications or exacerbation of co-morbid disease. Severe: persistent organ failure, that is, organ failure \>48 h. Local complications are peripancreatic fluid collections, pancreatic and peripancreatic necrosis (sterile or infected), pseudocyst and walled-off necrosis (sterile or infected).
Rate of ERCP-related perforation
Perforation was established according to Cotton criteria, Mild: slight leakage of fluid or contrast dye, manageable through fluid administration and suction therapy ≤3 days Moderate: definite perforation required to be managed for 4-10 days Severe: management for more than 10 days or requiring for percutaneous or surgical intervention.
Rate of ERCP-related infection
Infection was established according to Cotton criteria. Mild: temperature \>38# for 24-48h Moderate: Febrile illness requiring \>3 days of hospital treatment; endoscopic or percutaneous interventions; Severe: septic shock or requiring surgery.
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