Pre-ERCP infusion of semapimod, a mitogen-activated protein kinases inhibitor, lowers post-ERCP hyperamylasemia but not pancreatitis incidence

Background: Acute pancreatitis and hyperamylasemia are frequent complications of an ERCP. Semapimod is a synthetic guanylydrazone that inhibits the mitogen-activated protein kinase (MAPK) pathway, macrophage activation, and the production of several inflammatory cytokines. Objective: This study evaluated whether intravenous (IV) administration of semapimod given before an ERCP reduces the incidence of post-ERCP hyperamylasemia and pancreatitis. Design: A single-center, randomized, double-blinded, controlled trial. Setting: An academic medical center. Patients: Between 2001 and 2005, 242 patients who were undergoing a therapeutic ERCP at our institution were included. Intervention: Patients received a single IV close of semapimod or a placebo before an ERCP Main Outcome Measurements: The occurrence of post-ERCP pancreatitis, as well as post-ERCP hyperamylasemia. Results: The incidence of hyperamylasemia was significantly reduced (29.8% vs 18.4% P =.031). Moreover, semapimod administration significantly lowered the levels of amylase during the first 24 hours after the ERCP. The incidence of clinical pancreatitis was reduced by 40%, without reaching statistical significance (14.9 vs 9.1%; P = .117). Limitations: A relatively, small single-center study. One dose of semapimod was used. Conclusions: A single close of IV semapimod 1 hour before an ERCP is safe and exerts a biological effect, demonstrated by a statistically significant reduction of the incidence of hyperamylasemia and the levels of post-ERCP amylase. A protective effect for the development of post-ERCP pancreatitis could not be convincingly demonstrated.