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Prevention of Esophageal Varices by Beta-Adrenergic Blockers

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00006398
First Posted: October 6, 2000
Last Update Posted: June 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Yale University
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
October 5, 2000
October 6, 2000
June 1, 2017
August 1993
September 2002   (Final data collection date for primary outcome measure)
Varices [ Time Frame: 6 years ]
Development of varices
Not Provided
Complete list of historical versions of study NCT00006398 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Prevention of Esophageal Varices by Beta-Adrenergic Blockers
Randomized, Double-Blind Study of Timolol (A Nonselective Beta-Adrenergic Blocker) vs Placebo to Prevent Complications of Hepatic Portal Hypertension in Patients With Cirrhosis
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).
Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Esophageal and Gastric Varices
  • Liver Cirrhosis
  • Portal Hypertension
  • Drug: Timolol Maleate
  • Drug: Placebo
  • Experimental: Timolol Maleate
    Dose titrated from 5 mg per day to up to 80 mg per day depending on heart rate
    Intervention: Drug: Timolol Maleate
  • Placebo Comparator: Placebo
    Timelol placebo
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
213
September 2002
September 2002   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years to 75 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Spain,   United Kingdom,   United States
 
 
NCT00006398
Timolol (completed)
R01DK046580 ( U.S. NIH Grant/Contract )
YALESM 6618 ( Other Identifier: Yale School of Medicine )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Yale University
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
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP