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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Leiden University Medical Center
Sponsor:
Collaborators:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Free University Medical Center
Haga Hospital
Universitaire Ziekenhuizen Leuven
Ziekenhuis Netwerk Antwerpen (ZNA)
Information provided by (Responsible Party):
Dr. M.J.Coenraad, Leiden University Medical Center
ClinicalTrials.gov Identifier:
NCT01618890
First received: June 11, 2012
Last updated: February 6, 2014
Last verified: February 2014
  Purpose

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

Condition Intervention Phase
Acute Bleeding Esophageal Varices
Liver Cirrhosis
Procedure: Hepatic venous pressure gradient measurement
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Leiden University Medical Center:

Primary Outcome Measures:
  • First variceal bleeding episodes [ Time Frame: two years of follow-up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Mortality [ Time Frame: two years ] [ Designated as safety issue: No ]
  • Occurrence of other cirrhosis-related complications [ Time Frame: two years ] [ Designated as safety issue: No ]
    ascites spontaneous bacterial peritonitis hepatic encephalopathy hepatorenal syndrome hepatocellular carcinoma

  • Costs of treatments [ Time Frame: two years ] [ Designated as safety issue: No ]
  • Adverse effects [ Time Frame: two years ] [ Designated as safety issue: Yes ]
    Adverse effects associated with NSBB therapy, endoscopic band ligation, hepatic venous pressure gradient


Estimated Enrollment: 78
Study Start Date: September 2012
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HVPG-propranolol arm 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.

Other Names:
  • Hepatic venous pressure measurement
  • Endoscopic variceal band ligation
  • Propranolol
No Intervention: Propranolol arm

  Hide Detailed Description

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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

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 or D)
  • Refractory ascites
  • Hepatorenal syndrome
  • Prior treatment or prophylaxis for esophageal varices or varices bleeding (propranolol use, TIPS, endoscopic banding ligation, endoscopic sclerotherapy)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01618890

Contacts
Contact: Minneke Coenraad, Dr. +31-71-5269111 ext *9127 m.j.coenraad@lumc.nl

Locations
Belgium
Universitaire Ziekenhuizen Leuven Recruiting
Leuven, Belgium
Contact: Frederik Nevens, Prof. dr.         
Netherlands
Academisch Medisch Centrum Recruiting
Amsterdam, Netherlands
Contact: Ulrich Beuers, Prof.dr.         
Free University Medical Centre Recruiting
Amsterdam, Netherlands
Contact: Karin van Nieuwkerk, Dr.         
Leiden University Medical Centre Recruiting
Leiden, Netherlands, 2333 ZA
Contact: Minneke Coenraad, Dr.    +31-71-5269111 ext 99127    m.j.coenraad@lumc.nl   
Haga Hospital Recruiting
The Hague, Netherlands
Contact: Jan Nicolaï, Dr.         
Sponsors and Collaborators
Leiden University Medical Center
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Free University Medical Center
Haga Hospital
Universitaire Ziekenhuizen Leuven
Ziekenhuis Netwerk Antwerpen (ZNA)
Investigators
Principal Investigator: Minneke Coenraad, Dr. Leiden University Medical Centre
  More Information

No publications provided

Responsible Party: Dr. M.J.Coenraad, Dr., Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT01618890     History of Changes
Other Study ID Numbers: LUMC-40226
Study First Received: June 11, 2012
Last Updated: February 6, 2014
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Leiden University Medical Center:
Prevention
Esophageal variceal bleeding
Hepatic Venous Pressure Gradient
Betablocker therapy

Additional relevant MeSH terms:
Hemorrhage
Liver Cirrhosis
Esophageal and Gastric Varices
Gastrointestinal Hemorrhage
Pathologic Processes
Liver Diseases
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Hypertension, Portal
Adrenergic beta-Antagonists
Propranolol
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on September 22, 2014