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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.
First Received: February 24, 2000   Last Updated: September 8, 2008   History of Changes
Sponsors and Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Yale University
Information provided by: Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier: NCT00004641
  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 II

MedlinePlus related topics: Cirrhosis Esophagus Disorders High Blood Pressure Varicose Veins
Drug Information available for: Timolol Timolol maleate
U.S. FDA Resources
Study Type: Interventional
Study Design: Prevention, Randomized, Double-Blind, Placebo Control, Efficacy Study
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

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

Publications:
Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):
Study ID Numbers: 199/11640, YALESM-6618
Study First Received: February 24, 2000
Last Updated: September 8, 2008
ClinicalTrials.gov Identifier: NCT00004641     History of Changes
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

Study placed in the following topic categories:
Neurotransmitter Agents
Liver Diseases
Adrenergic Agents
Fibrosis
Gastrointestinal Diseases
Vascular Diseases
Cardiovascular Agents
Liver Cirrhosis
Hypertension, Portal
Antihypertensive Agents
Hepatitis
Digestive System Diseases
Varicose Veins
Esophageal Disorder
Portal Hypertension
Esophageal and Gastric Varices
Adrenergic beta-Antagonists
Adrenergic Antagonists
Anti-Arrhythmia Agents
Timolol
Esophageal Diseases
Esophageal Varices
Liver Cirrhosis, Alcoholic
Hypertension

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

ClinicalTrials.gov processed this record on May 07, 2009