A Study to Prevent Complications of High Blood Pressure Caused by Hepatitis in Patients With Cirrhosis

Liver Cirrhosis Clinical Trial

Official title:

Randomized, Double-Blind Study of Timolol (A Nonselective Beta-Adrenergic Blocker) vs Placebo to Prevent Complications of Hepatic Portal Hypertension in Patients With Cirrhosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004641
• Other study ID #: 199/11640
• Secondary ID: YALESM-6618
• Status: Completed
• Phase: Phase 2
• First received: February 24, 2000
• Last updated: September 8, 2008
• Start date: May 1993

Study information

• Verified date: September 2008
• Source: Office of Rare Diseases (ORD)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

OBJECTIVES:

I. Evaluate the efficacy of a certain drug in preventing intestinal complications in patients with cirrhosis and high blood pressure in the hepatic portal vein.

II. Evaluate vein pressure measurements to predict the development of internal bleeding.

Description:

PROTOCOL OUTLINE: This is a randomized, double-blind study. Patients are stratified by participating institution, cirrhosis etiology, and hepatic venous pressure gradient.

The dose of oral timolol is titrated over 28 days. Patients are then randomly assigned to daily timolol at the titrated dose or a placebo if successful titration is achieved by day 28, and the final titration dose is maintained for at least 10 days. Timolol is discontinued prior to randomization.

Criteria for removal from study include esophageal or gastric varices, significant bleeding or hemorrhage, timolol-induced hepatic encephalopathy, and liver transplantation.

Patients are followed every 3 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 212
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 74 Years

Eligibility

• Biopsy-proven cirrhosis of any etiology, including hepatitis B or C. No primary biliary cirrhosis.

• Hepatic venous pressure gradient (HVPG) at least 6 mm Hg.

• Histologic slides available for review OR liver-spleen scan compatible with cirrhosis if biopsy older than 5 years. Repeat biopsy required if scan incompatible OR HVPG at least 10 mm Hg and any of the following clinical features suggestive of cirrhosis: telangiectasias, palmar erythema, muscle wasting, liver hard and nodular, or splenomegaly, hypoalbuminemia, hyperbilirubinemia, or prolonged prothrombin time, liver-spleen scan with colloid shift to spleen or bone marrow, collaterals visualized by ultrasound or CT.

• Gastroesophageal varices negative by endoscopy within 3 months prior to randomization.

• Independent verification by 2 endoscopists required.

• No ascites requiring specific treatment, e.g., diuretics, paracentesis, peritoneovenous shunt.

• Ascites controlled by salt restriction alone allowed.

• No splenic or portal vein thrombosis by Doppler-ultrasound.

• No primary sclerosing cholangitis.

• No radiologically or histologically proven hepatocellular carcinoma.

Prior/Concurrent Therapy

• At least 1 month since participation in another pharmacologic clinical trial.

• At least 1 month since drugs that may affect splanchnic hemodynamics or portal pressure, e.g., beta-blockers, clonidine prazosin, nitrates molsidomine

Patient Characteristics

• Life expectancy: At least 1 year

• Other: Eligibility determined on an individual basis for the following: aortic valve stenosis, atrioventricular block, asthma, chronic obstructive pulmonary disease with positive bronchoconstrictive test, heart failure, hypersensitivity to beta-blockers, insulin-dependent diabetes, organic psychosis, peripheral vascular disease.

• No alcohol intake during titration period.

• No pregnant women.

• Effective contraception required of fertile women.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Esophageal and Gastric Varices
• Hypertension
• Hypertension, Portal
• Liver Cirrhosis

Intervention

Drug:
• timolol

Locations

Country	Name	City	State
United States	Yale University School of Medicine	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Yale University

Country where clinical trial is conducted

United States, 

References & Publications (1)

Wongcharatrawee S, Groszmann RJ. Diagnosing portal hypertension. Baillieres Best Pract Res Clin Gastroenterol. 2000 Dec;14(6):881-94. Review. — View Citation