Hepatic Venous Pressure Gradient-guided Versus Standard Beta-blocker Therapy in Primary Prevention of Variceal Bleeding

Last updated: September 27, 2019
Sponsor: Leiden University Medical Center
Overall Status: Active - Recruiting

Phase

3

Condition

Hemorrhage

Hyponatremia

Hepatic Fibrosis

Treatment

N/A

Clinical Study ID

NCT01618890
LUMC-40226
  • Ages 18-75
  • All Genders

Study Summary

Study hypothesis:

Hepatic venous pressure gradient (HVPG)-directed primary prophylaxis with nonselective beta-blocker therapy (NSBB) leads to a reduction in first variceal bleeding episodes and is cost-effective in the long term.

Study design:

A multi-center randomized controlled study comparing nonselective beta-blocker therapy guided by the hemodynamic response as determined by the difference in HVPG before and after starting oral NSBB therapy, to standard heart rate-guided NSBB therapy in patients with esophageal varices due to liver cirrhosis without a history of esophageal variceal hemorrhage.

Primary study parameters/outcome of the study:

First variceal bleeding episodes occurring within the first two years.

Secondary study parameters/outcome of the study:

  • Mortality

  • Occurrence of other cirrhosis-related complications

  • Occurrence of hepatocellular carcinoma

  • Costs of treatments

  • Adverse effects

Eligibility Criteria

Inclusion

Inclusion Criteria: Patients with liver cirrhosis Large (≥5 mm) esophageal varices

Exclusion

Exclusion Criteria:

  • History of esophageal variceal hemorrhage

  • Pregnancy

  • Contraindications to beta-blocker therapy

  • Esophageal varices in the absence of liver cirrhosis

  • Intermediate, advanced or terminal stage hepatocellular carcinoma (BCLC stage B, C orD)

  • Refractory ascites

  • Hepatorenal syndrome

  • Prior treatment or prophylaxis for esophageal varices or varices bleeding (propranololuse, TIPS, endoscopic banding ligation, endoscopic sclerotherapy)

Study Design

Total Participants: 78
Study Start date:
September 01, 2012
Estimated Completion Date:
December 31, 2022

Study Description

Background of the study:

About 50% of cirrhotic patients who use nonselective beta-blockers (NSBB) for primary prevention of variceal bleeding do not reach target hemodynamic response, defined as HVPG < 12 mmHg or a > 20% decrease in HVPG from baseline. These so-called hemodynamic nonresponding patients have significantly higher rate of first esophageal variceal hemorrhage as compared to patients who do respond to NSBB.

International institutions that publish guidelines differ in their recommendations concerning HVPG monitoring. As a result, practice currently varies widely.

The investigators hypothesize that HVPG-directed primary prophylaxis leads to a reduction in first variceal bleeding episodes and is cost-effective in the long term.

Objective of the study:

To determine cost-effectiveness of hepatic venous pressure gradient (HVPG)-guided nonselective beta-blocker therapy as compared to standard heart rate-guided beta-blocker therapy in the primary prevention of esophageal variceal bleeding in cirrhotic patients.

Study design:

A multi-center randomized controlled study comparing nonselective beta-blocker therapy guided by the hemodynamic response as determined by the difference in HVPG before and after starting oral nonselective beta-blockers, to standard heart rate-guided nonselective beta-blocker therapy in patients with esophageal varices due to liver cirrhosis.

Study population:

Patients with liver cirrhosis and large (>5 mm) esophageal varices without a history of esophageal variceal hemorrhage.

Intervention:

-In HVPG-group: Perform baseline HVPG measurement, then start propranolol 20 mg orally twice daily (BID), increase the dose stepwise with 3 days interval to decrease the heart rate to maximum tolerated dose. After 4 weeks a second HVPG is performed.

In hemodynamic responders (who reach target decrease in HVPG) NSBB are continued until end of follow-up.

In hemodynamic nonresponders (who do not reach target decrease in HVPG), NSBB are continued and repeated endoscopic band ligation is performed with 2-4 weeks interval until complete obliteration of large varices.

-In control group: Start propranolol 20 mg BID, increase the dose stepwise with 3 days interval to maximum heart rate-guided tolerated dose.

Primary study parameters/outcome of the study:

First variceal bleeding episodes occurring within the first two years.

Secondary study parameters/outcome of the study:

Mortality Occurrence of other cirrhosis-related complications Occurrence of hepatocellular carcinoma Costs of treatments Adverse effects

Connect with a study center

  • Universitair Ziekenhuis Antwerpen

    Antwerpen, B-2650
    Belgium

    Active - Recruiting

  • Universitaire Ziekenhuizen Leuven

    Leuven,
    Belgium

    Active - Recruiting

  • Academisch Medisch Centrum

    Amsterdam,
    Netherlands

    Active - Recruiting

  • Free University Medical Centre

    Amsterdam,
    Netherlands

    Active - Recruiting

  • Leiden University Medical Centre

    Leiden, 2333 ZA
    Netherlands

    Active - Recruiting

  • Erasmus Medical Centre

    Rotterdam,
    Netherlands

    Site Not Available

  • Haga Hospital

    The Hague,
    Netherlands

    Active - Recruiting

  • UMC Utrecht

    Utrecht,
    Netherlands

    Site Not Available

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