Secondary Prophylaxis of Gastrointestinal Bleeding in Cirrhotic Patients Using THALIDOMIDE

• Status: Withdrawn
• Trial end date: 2010-01-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Cleveland Clinic
• Collaborator: Celgene Corporation
• Treatments: Nadolol; Propranolol; Thalidomide; Timolol

Criteria

Inclusion Criteria:

• Endoscopic confirmation or portal hypertension related GI bleeding

• Over the age of 18 with the ability to willingly sign an informed consent

• Adequate performance status and cognitive ability

• Patients must be willing to comply with all FDA-mandated prescribing and safety while taking Thalidomide

• Hemodynamically stable with no evidence of ongoing bleeding (defined as a Hgb that has not varied by more than 10% over 12 hour period.)

Exclusion Criteria:

• No other serious illness or medical condition including unstable cardiac disease requiring treatment, new onset crescendo or rest angina. Stable exertional angina is acceptable.

• No history of significant neurological or psychiatric disorders including psychotic disorders, dementia, or seizures or active infection