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Prevention of Esophageal Varices by Beta-Adrenergic Blockers

This study has been completed.
Sponsor:
Information provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00006398
First received: October 5, 2000
Last updated: January 12, 2010
Last verified: January 2010
  Purpose

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).


Condition Intervention Phase
Esophageal and Gastric Varices
Liver Cirrhosis
Portal Hypertension
Drug: Timolol Maleate
Phase 3

Study Type: Interventional
Study Design: 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 National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Study Start Date: August 1993
Estimated Study Completion Date: March 1998
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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 ClinicalTrials.gov identifier: NCT00006398

Locations
United States, Connecticut
Yale University Sch. of Medicine
New Haven, Connecticut, United States, 06520
VA CT Healthcare System
West Haven, Connecticut, United States, 06516
United States, Massachusetts
The Faulkner Hospital
Boston, Massachusetts, United States, 02130
Spain
Hospital Clinic I Provincial de Barcelona
Barcelona, Catalonia, Spain
United Kingdom
Royal Free Hospital
Hampstead, London, United Kingdom, NW32QG
Sponsors and Collaborators
Investigators
Principal Investigator: Roberto J Groszmann, M.D. Yale University School of Med.
Investigator: Norman Grace, M.D. Tufts University
Investigator: Jaime Bosch, M.D. University of Barcelona
Investigator: Andrew Burroughs, M.D. University of London
Investigator: Guadalupe Garcia-Tsao, M.D. Yale University
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00006398     History of Changes
Other Study ID Numbers: Timolol (completed), RO1 DK46580, YALESM, 6618
Study First Received: October 5, 2000
Last Updated: January 12, 2010
Health Authority: United States: Federal Government

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
cirrhosis
esophageal varices
variceal hemorrhage
beta-adrenergic blocker

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

ClinicalTrials.gov processed this record on November 27, 2014