Prevention of Esophageal Varices by Beta-Adrenergic Blockers
Information source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Esophageal and Gastric Varices; Liver Cirrhosis; Portal Hypertension
Intervention: Timolol Maleate (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Official(s) and/or principal investigator(s):
Roberto J Groszmann, M.D., Principal Investigator, Affiliation: Yale University School of Med.
Norman Grace, M.D., Affiliation: Tufts University
Jaime Bosch, M.D., Affiliation: University of Barcelona
Andrew Burroughs, M.D., Affiliation: University of London
Guadalupe Garcia-Tsao, M.D., Affiliation: Yale University
Summary
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).
Clinical Details
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
Study design: Prevention, Double-Blind
Eligibility
Minimum age: 18 Years.
Maximum age: 75 Years.
Gender(s): Both.
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.
Locations and Contacts
Hospital Clinic I Provincial de Barcelona, Barcelona, Catalonia, Spain
VA CT Healthcare System, West Haven, Connecticut 06516, United States
Yale University Sch. of Medicine, New Haven, Connecticut 06520, United States
Royal Free Hospital, Hampstead, London NW32QG, United Kingdom
The Faulkner Hospital, Boston, Massachusetts 02130, United States
Additional Information
Related publications: Sarin SK, Groszmann RJ, Mosca PG, Rojkind M, Stadecker MJ, Bhatnagar R, Reuben A, Dayal Y. Propranolol ameliorates the development of portal-systemic shunting in a chronic murine schistosomiasis model of portal hypertension. J Clin Invest. 1991 Mar;87(3):1032-6. Escorsell A, Ferayorni L, Bosch J, Garcia-Pagan JC, Garcia-Tsao G, Grace ND, Rodes J, Groszmann RJ. The portal pressure response to beta-blockade is greater in cirrhotic patients without varices than in those with varices. Gastroenterology. 1997 Jun;112(6):2012-6.
Starting date: August 1993
Ending date: March 1998
Last updated: May 4, 2006
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