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

NCT01618890 | Unknown Phase 3 DMC

• 1 other identifier: LUMC-40226
• Study Type: interventional
• Target: 78
• Locations: 2 countries
• Sites: 6

Brief 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

Conditions

Acute Bleeding Esophageal Varices; Liver Cirrhosis

Keywords

Prevention; Esophageal variceal bleeding; Hepatic Venous Pressure Gradient; Betablocker therapy

Outcome Measures

Primary Outcomes (1)

• First variceal bleeding episodes

  First variceal bleeding episodes

  two years of follow-up

Secondary Outcomes (4)

• Mortality

  two years

• Occurrence of other cirrhosis-related complications

  two years

• Costs of treatments

  two years

• Adverse effects

  two years

Study Arms (2)

HVPG-propranolol arm

EXPERIMENTAL

A baseline hepatic venous pressure gradient measurement (HVPG measurement) is performed in day-care setting. After this procedure propranolol is started at 20 mg BID. with dose escalation as described in the propranolol arm. A second HVPG measurement is performed at 4 weeks after adequate propranolol therapy. In patients who reach target HVPG reduction (responders), propranolol is continued at the same dose without routine control endoscopy. In patients who do not reach target HVPG reduction (nonresponders), endoscopic band ligation is performed in day-care setting with intervals of 2-4 weeks until complete obliteration of varices. Follow-up endoscopy with 6 months interval is performed to detect and treat recurrent large varices.

Procedure: Hepatic venous pressure gradient measurement

Propranolol arm

NO INTERVENTION

Propranolol start 20 mg BID. orally with dose escalation based on heart frequency (HF) with 3-days interval to the maximum tolerated dose. No routine control endoscopy is required.

Interventions

Hepatic venous pressure gradient measurement PROCEDURE

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.

Also known as: Hepatic venous pressure measurement, Endoscopic variceal band ligation, Propranolol

HVPG-propranolol arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with liver cirrhosis Large (≥5 mm) esophageal varices

You may not qualify if:

• 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 or D)
• Refractory ascites
• Hepatorenal syndrome
• Prior treatment or prophylaxis for esophageal varices or varices bleeding (propranolol use, TIPS, endoscopic banding ligation, endoscopic sclerotherapy)

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• Free University Medical Center: collaborator
• Haga Hospital: collaborator
• Universitaire Ziekenhuizen KU Leuven: collaborator
• Ziekenhuis Netwerk Antwerpen (ZNA): collaborator

Study Sites (6)

Universitair Ziekenhuis Antwerpen

Antwerp, B-2650, Belgium

RECRUITING

Universitaire Ziekenhuizen Leuven

Leuven, Belgium

RECRUITING

Academisch Medisch Centrum

Amsterdam, Netherlands

RECRUITING

Free University Medical Centre

Amsterdam, Netherlands

RECRUITING

Leiden University Medical Centre

Leiden, 2333 ZA, Netherlands

RECRUITING

Haga Hospital

The Hague, Netherlands

RECRUITING

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Propranolol

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Minneke Coenraad, Dr.

  Leiden University Medical Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Minneke Coenraad, Dr.

CONTACT

+31-71-5269111; m.j.coenraad@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: June 11, 2012
• First Posted: June 13, 2012
• Study Start: September 1, 2012
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2022
• Last Updated: September 30, 2019

Record last verified: 2019-09

Locations

NL (4); BE (2)