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

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.

• Authors: David J van Westerloo, Erik A Rauws, Daan Hommes, Alex F de Vos, Tom van der Poll, Barbara L Powers, Paul Fockens, Marcel G W Dijkgraaf, Marco J Bruno
• Journal: Gastrointestinal endoscopy (Gastrointest Endosc) Vol. 68 Issue 2 Pg. 246-54 (Aug 2008) ISSN: 1097-6779 [Electronic] United States
• PMID: 18455169 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Hydrazones
• semapimod

Topics

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