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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

February 24, 2000
September 8, 2008
May 1993
August 2007   (final data collection date for primary outcome measure)
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Complete list of historical versions of study NCT00004641 on ClinicalTrials.gov Archive Site
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A Study to Prevent Complications of High Blood Pressure Caused by Hepatitis in Patients With Cirrhosis
Randomized, Double-Blind Study of Timolol (A Nonselective Beta-Adrenergic Blocker) vs Placebo to Prevent Complications of Hepatic Portal Hypertension in Patients With Cirrhosis

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Masking: Double-Blind
Primary Purpose: Prevention
  • Hypertension, Portal
  • Liver Cirrhosis
  • Esophageal and Gastric Varices
Drug: timolol
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
212
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August 2007   (final data collection date for primary outcome measure)
  • 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.
Both
18 Years to 74 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00004641
199/11640, YALESM-6618
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Yale University
Study Chair: Robert J. Groszmann Yale University
Office of Rare Diseases (ORD)
September 2008

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