Pancreatitis is the most common major complication of diagnostic and therapeutic ERCP occurring in 1-10% of patients. Although ERCP provides a unique opportunity to administer prophylactic therapy to limit the frequency and seventy of post-procedure pancreatitis, no agent thus far studied has been effective in this regard. Corticosteroids have been shown to significantly elevate the functional C-1-esterase inhibitor levels, one of the major circulating protease inhibitors. Moreover, many of the events in the cascade of autodigestion may be inhibited by corticosteroids (e.g. blockage of complement and contact system activation). The aims of this study are to 1) determine whether prophylactic corticosteroids will reduce the frequency and severity of post-procedure pancreatitis, and 2) identify patient and procedure risk factors predictive of the development of post-ERCP pancreatitis. METHODS: This is a randomized prospective double-blind multicenter study. Patients receive either oral prednisone (40 mg) or placebo 15 hours and 3 hours prior to ERCP. A 160 variable database was prospectively collected on randomized patients. Standardized criteria are used to diagnose and grade the severity of post-procedure pancreatitis (GI Endosc 1991;37:383). Pancreatitis rates will be compared between the groups. Secondary analysis will involve logistic regression using patient and procedure characteristics to predict the risk of pancreatitis and the effectiveness of prophylaxis. RESULTS: 493 patients have been randomized. Pancreatitis has occurred in 62 (12.6%) and was graded mild in 40 (8.1%), moderate in 16 (3.2%) and severe in 6 (1.2%). There were no episodes of pancreatitis occurring after randomization and prior to the procedure. Side effects of the placebo and drug occurred in <2% and were primarily limited to mild dyspepsia. The projected enrollment is 2000; an interim analysis will be performed at 50% patient accrual. CONCLUSIONS: Although the risk factors for ERCP-induced pancreatitis have been identified, attempts to prevent this complication have been disappointing. Systemic corticosteroids may be a promising new therapy to reduce the incidence and severity of this complication.