Prevention of Esophageal Varices by Beta-Adrenergic Blockers

Phase 3

Completed

• Conditions: Liver Cirrhosis; Esophageal and Gastric Varices; Portal Hypertension
• Interventions: Drug: Timolol Maleate; Drug: Placebo

• Registration Number: NCT00006398
• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief Summary

The purpose of this study is to learn whether timolol is useful in preventing or delaying the appearance of gastroesophageal varices, a complication that may develop in the future as a consequence of liver disease. Cirrhosis causes an increased resistance of blood flowing through the liver. This leads to an increased pressure in the portal vein (the vein that takes blood to your liver). High portal pressure is responsible for the appearance of complications of chronic liver disease such as varices and variceal bleeding (bleeding from veins in your esophagus). Timolol belongs to a group of medications called beta-blockers. Beta-blockers decrease high portal pressure and previous studies have shown that beta-blocker pills are useful in preventing bleeding from varices in patients who already have varices. A more desirable effect would be if these pills could prevent not only bleeding from varices but the appearance of varices (and therefore of bleeding).

Detailed Description

Not available

Study Timeline

• Study Start: 1993-08
• Study First Submitted: 2000-10-05
• Study First Submitted QC: 2000-10-05
• Study First Posted: 2000-10-06
• Primary Completion: 2002-09
• Study Completion: 2002-09
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-30
• Last Update Posted: 2017-06-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 213

Inclusion Criteria

• Liver biopsy compatible with cirrhosis.
• Absence of gastroesophageal varices.
• An increased hepatic venous pressure gradient (HVPG) (6mmHg).
• Age over 18 and below 76 years.
• Informed, written consent.
• Absence of exclusion criteria.

Exclusion Criteria

• Presence of ascites that requires specific treatment (diuretics, paracentesis, peritoneo-venous shunt, etc).
• Proven hepatocellular carcinoma by radiological or histological criteria.
• Splenic or portal vein thrombosis by Doppler-ultrasound.
• Presence of any concurrent disease that is expected to decrease life expectancy to less than one year.
• Patients taking diuretics, beta-blockers, clonidine, prazosin, nitrates, molsidomine and any drug which may have an effect on splanchnic hemodynamics/portal pressure.
• Patients participating in other pharmacological randomized clinical trials.
• Patients with primary biliary cirrhosis and primary sclerosing cholangitis will also be excluded since these entities have a slower progression of the disease, are usually enrolled in other clinical trials and are transplanted at an earlier stage.
• Contraindications to beta-blockers: asthma, COPD with positive broncoconstrictive test, heart failure, A-V block, aortic valve stenosis, organic psychosis, insulin-dependent diabetes, hypersensitivity to beta-blockers.
• Women who are pregnant, nursing or of childbearing potential and who are not using oral or mechanical contraception.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Timolol Maleate	Timolol Maleate	Dose titrated from 5 mg per day to up to 80 mg per day depending on heart rate
Placebo	Placebo	Timelol placebo

Primary Outcome Measures

Name	Time	Method
Varices	6 years	Development of varices

Trial Locations

Locations (5)

Royal Free Hospital; 🇬🇧 Hampstead, London, United Kingdom

The Faulkner Hospital; 🇺🇸 Boston, Massachusetts, United States

Hospital Clinic I Provincial de Barcelona; 🇪🇸 Barcelona, Catalonia, Spain

VA CT Healthcare System; 🇺🇸 West Haven, Connecticut, United States

Yale University Sch. of Medicine; 🇺🇸 New Haven, Connecticut, United States