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 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.


METHODS
A single-center, randomized, double-blinded, controlled trial.


METHODS
An academic medical center.


METHODS
Between 2001 and 2005, 242 patients who were undergoing a therapeutic ERCP at our institution were included.


METHODS
Patients received a single IV dose of semapimod or a placebo before an ERCP.


METHODS
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).


CONCLUSIONS
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.
van Westerloo
David J
DJ
Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Rauws
Erik A
EA
Hommes
Daan
D
de Vos
Alex F
AF
van der Poll
Tom
T
Powers
Barbara L
BL
Fockens
Paul
P
Dijkgraaf
Marcel G W
MG
Bruno
Marco J
MJ
D000368:Aged; D002760:Cholangiopancreatography, Endoscopic Retrograde / Q000009:adverse effects* / Q000379:methods; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006835:Hydrazones / Q000008:administration & dosage*; D034321:Hyperamylasemia / Q000453:epidemiology / Q000517:prevention & control*; D015994:Incidence; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010182:Pancreatic Diseases / Q000000981:diagnostic imaging / Q000601:surgery; D010195:Pancreatitis / Q000453:epidemiology / Q000517:prevention & control*; D011300:Preoperative Care / Q000379:methods; D011336:Probability; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D000813:Anilides; D006146:Guanidines
D006835:Hydrazones; C097256:semapimod; D000813:Anilides; D006146:Guanidines