NCT01618890

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

A Multi-center Randomized Controlled Study of Primary Prevention of Esophageal Variceal Bleeding in Cirrhotic Patients Treated With HVPG-guided Beta- Blocker Therapy or Standard Heart Rate-guided Beta-blocker Therapy

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 78 (estimated)
• Sponsor: Leiden University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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

Detailed 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

Conditions

• Acute Bleeding Esophageal Varices
• Liver Cirrhosis

Interventions

Type	Name	Description
PROCEDURE	Hepatic venous pressure gradient measurement	Perform baseline HVPG measurement, then start propranolol 20 mg orally twice daily (BID), increase the dose stepwise to maximum tolerated dose. After 4 weeks a second HVPG is performed. In hemodynamic nonresponders from the study arm, repeated endoscopic band ligation is performed in daycare setting with intervals of 2-4 weeks. In hemodynamic responders (HVPG second measurement\< 12 mmHg or \>20% reduction in HVPG compared to baseline) beta-blockers are continued until end of follow-up.

Timeline

• Start date: 2012-09-01
• Primary completion: 2020-12-01
• Completion: 2022-12-01
• First posted: 2012-06-13
• Last updated: 2019-09-30

Locations

6 sites across 2 countries: Belgium, Netherlands