Secondary Prophylaxis of Gastrointestinal Bleeding in Cirrhotic Patients Using THALIDOMIDE
Status:
Withdrawn
Trial end date:
2010-01-01
Target enrollment:
Participant gender:
Summary
The natural history of cirrhosis has a symptomatic and asymptomatic stage. The symptoms
include the development of ascites, hepatic encephalopathy, or variceal bleeding. The
development of portal hypertension represents a critical transition point in the natural
history of cirrhosis, contributing to, or directly responsible for all of these events. It is
defined by an increase in intrahepatic vascular resistance to portal venous inflow, with the
subsequent development of collateral vessels, such as esophageal or gastric varices. As
portal pressures rise over time, however, the resulting increase in variceal size and wall
tension translates into an increasing likelihood of rupture and bleeding, leading to death in
about 30% of patients. Over the last twenty years, data have emerged regarding the role of
tumor necrosis factor (TNFα) in portal hypertension from animal models as well as in vitro
experiments. Portal hypertension is a condition characterized by vasodilatation and a
hyperdynamic circulation, driven by relative overproduction of nitric oxide23. In animal
trials using inhibitors of TNF it has been shown to decrease the development of the
hyperdynamic circulatory state and portal pressure.24-25 Based on these data, investigators
have examined the role of TNF inhibition with thalidomide. Significant improvement in
blocking the development of the hyperdynamic circulation and portal pressures was
demonstrated.26 Human trials have also show the efficacy of thalidomide in reducing portal
pressures. In that these trials have shown promising results further investigation is