Secondary Prophylaxis of Gastrointestinal Bleeding in Cirrhotic Patients Using THALIDOMIDE

NCT00787436 | Withdrawn Phase 3 DMC

• 5 other identifiers: CEL-20237IRB00000536FWA0000536734-0714585OSR-20070905-01
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Gastrointestinal Hemorrhage; Portal Hypertension

Keywords

portal hypertension; Gastroesophageal; Varices; Liver disease; cirrhosis

Outcome Measures

Primary Outcomes (1)

• The proposed study would use a novel approach to prophylaxis, using thalidomide, an oral TNF inhibitor, in conjunction with a betablocker to prevent rebleeding of upper gastrointestinal bleeding in patients with cirrhosis and portal hyperte

  16 week duration

Secondary Outcomes (1)

• The secondary endpoint is to examine the impact on progression of liver disease in this population, including development of other complications of chronic liver disease, such as encephalopathy, hepatorenal syndrome and patient survival

  16 week duration

Study Arms (2)

1

NO INTERVENTION

Standard of care with normal treatment

Thalidomide

ACTIVE COMPARATOR

Standard of care and treatment using Thalidomide

Drug: Thalidomide

Interventions

Thalidomide DRUG

Medical therapy has been used to decrease upper gastrointestinal bleeding in cirrhotics Non Selective beta blockers have been shown to effectively decrease the portal venous pressure

Also known as: propranolol, nadolol, timolol

Thalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.)

You may not qualify if:

• 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

Sponsors & Collaborators

• The Cleveland Clinic: lead
• Celgene Corporation: collaborator

Study Sites (1)

Cleveland Clinic Foundation

Cleveland, Ohio, 44109, United States

Location

MeSH Terms

Conditions

Gastrointestinal Hemorrhage; Hypertension, Portal; Varicose Veins; Liver Diseases; Fibrosis

Interventions

Thalidomide; Propranolol; Nadolol; Timolol

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Thiadiazoles; Thiazoles; Sulfur Compounds; Azoles; Morpholines; Oxazines

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2008
• First Posted: November 7, 2008
• Study Start: May 1, 2006
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: July 31, 2013

Record last verified: 2013-07

Locations

US (1)