Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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

This study has been completed.
Yale University
Information provided by:
Office of Rare Diseases (ORD) Identifier:
First received: February 24, 2000
Last updated: September 8, 2008
Last verified: September 2008


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.

Condition Intervention Phase
Hypertension, Portal
Liver Cirrhosis
Esophageal and Gastric Varices
Drug: timolol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Prevention
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

Resource links provided by NLM:

Further study details as provided by Office of Rare Diseases (ORD):

Estimated Enrollment: 212
Study Start Date: May 1993
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Detailed 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.


Ages Eligible for Study:   18 Years to 74 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00004641

United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06510
Sponsors and Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Yale University
Study Chair: Robert J. Groszmann Yale University
  More Information

Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00004641     History of Changes
Other Study ID Numbers: 199/11640
Study First Received: February 24, 2000
Last Updated: September 8, 2008

Keywords provided by Office of Rare Diseases (ORD):
Cruveilhier-Baumgarten Syndrome
Esophageal Varices
Gastric Varices
Esophageal Varix
Gastric Varix
Alcoholic Cirrhosis

Additional relevant MeSH terms:
Liver Cirrhosis
Esophageal and Gastric Varices
Hypertension, Portal
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Liver Diseases
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents processed this record on April 24, 2017