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

Gastrointest Endosc. 2008 Aug;68(2):246-54. doi: 10.1016/j.gie.2008.01.034. Epub 2008 May 2.

Abstract

Background: Acute pancreatitis and hyperamylasemia are frequent complications of an ERCP. Semapimod is a synthetic guanylhydrazone 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 dose 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 dose 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cholangiopancreatography, Endoscopic Retrograde / adverse effects*
  • Cholangiopancreatography, Endoscopic Retrograde / methods
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Hydrazones / administration & dosage*
  • Hyperamylasemia / epidemiology
  • Hyperamylasemia / prevention & control*
  • Incidence
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Pancreatic Diseases / diagnostic imaging
  • Pancreatic Diseases / surgery
  • Pancreatitis / epidemiology
  • Pancreatitis / prevention & control*
  • Preoperative Care / methods
  • Probability
  • Prospective Studies
  • Reference Values
  • Risk Assessment
  • Statistics, Nonparametric
  • Treatment Outcome

Substances

  • Hydrazones
  • semapimod