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

This study has been completed.
Sponsor:
Collaborator:
Yale University
Information provided by:
Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:
NCT00004641
First received: February 24, 2000
Last updated: September 8, 2008
Last verified: September 2008
History of Changes
  Purpose

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.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
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:

U.S. FDA Resources

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.

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004641

Locations
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
Investigators
Study Chair: Robert J. Groszmann Yale University
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

ClinicalTrials.gov Identifier: NCT00004641     History of Changes
Other Study ID Numbers: 199/11640, YALESM-6618
Study First Received: February 24, 2000
Last Updated: September 8, 2008
Health Authority: United States: Federal Government

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:
Esophageal and Gastric Varices
Esophageal Diseases
Hypertension
Hypertension, Portal
Liver Cirrhosis
Fibrosis
Varicose Veins
Gastrointestinal Diseases
Digestive System Diseases
Liver Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
 Adrenergic beta-Antagonists
Timolol
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents

ClinicalTrials.gov processed this record on May 21, 2013