Although ERCP provides a unique opportunity to administer prophylactic therapy to limit the incidence and severity of post-procedure pancreatitis, no agent thus far studied has been effective in this regard. By elevating the functional C-1-esterase inhibitor levels and inhibiting many of the events in the cascade of autodigestion, systemic corticosteroids may reduce the incidence of post-ERCP pancreatitis. The aim of this randomized, double blind, controlled trial was to determine whether prophylactic corticosteroids will reduce the frequency and severity of post-ERCP pancreatitis. METHODS: Patients were randomized to receive either oral prednisone (40 mg) or placebo 15 hours and 3 hours prior to ERCP. A 160 variable database was prospectively collected by a defined protocol on patients undergoing diagnostic or therapeutic ERCP at 15 centers in the Midwest Pancreaticobiliary Group. Standardized criteria were used to diagnose and grade the severity of post-procedure pancreatitis (GI Endosc 1991;37:383). This is the interim analysis of nearly 50% of planned enrollment. RESULTS: PANCREATITIS SEVERITY Total with Therapy N Mild Moderate Severe pancreatitis Prednisone 464 49 (10.6%) 21 (4.5%) 3 (.6%) 73 (15.7%) Placebo 471 44 (9.3%) 17 (3.6%) 5 (1%) 66 (14.0%) p = .43 The groups were similar with regards to age, sex, body mass index (BMI), frequency of prior pancreatitis, type of procedure performed (diagnostic or therapeutic), difficulty of cannulation, frequency of precut sphincterotomy, pancreatic sphincterotomy, sphincter of Oddi (SO) dysfunction, SO manometry, pancreatic acinarization, chronic pancreatitis, number of pancreatic duct injections, and common bile duct diameter. CONCLUSIONS: 1) In this interim analysis, prophylactic oral corticosteroids was not shown to reduce the frequency or severity of post-ERCP pancreatitis. 2) The study is ongoing with planned enrollment of 1,000 patients into each intervention arm.