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

This study is not yet open for participant recruitment.
Verified June 2012 by Leiden University Medical Center
Sponsor:
Collaborators:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
UMC Utrecht
Free University Medical Center
Erasmus Medical Center
Haga Hospital
Medical Center Haaglanden
Universitaire Ziekenhuizen Leuven
Information provided by (Responsible Party):
Dr. M.J.Coenraad, Leiden University Medical Center
ClinicalTrials.gov Identifier:
NCT01618890
First received: June 11, 2012
Last updated: June 12, 2012
Last verified: June 2012
History of Changes
  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
Other: standard of care primary prevention with propranolol
 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:

U.S. FDA Resources

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 Other: standard of care primary prevention with propranolol
In control group: Start propranolol 20 mg BID, increase the dose stepwise with 3 days interval to maximum heart rate-guided tolerated dose.
Other Name: Propranolol

  Show Detailed Description

  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 and large (>5 mm) esophageal varices

Exclusion Criteria:

  • a history of esophageal variceal hemorrhage
  • pregnancy
  • contraindications to beta-blocker therapy
  • esophageal varices in the absence of liver cirrhosis
  Contacts and Locations
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 Not yet recruiting
Leuven, Belgium
Contact: Frederik Nevens, Prof. dr.            
Netherlands
Free University Medical Centre Not yet recruiting
Amsterdam, Netherlands
Contact: Karin van Nieuwkerk, Dr.            
Academisch Medisch Centrum Not yet recruiting
Amsterdam, Netherlands
Contact: Ulrich Beuers, Prof.dr.            
Leiden University Medical Centre
Leiden, Netherlands, 2333 ZA
Erasmus Medical Centre Not yet recruiting
Rotterdam, Netherlands
Contact: Eric Tjwa, Drs.            
Medical Centre Haaglanden Not yet recruiting
The Hague, Netherlands
Contact: Hanneke van Soest, Dr.            
Haga Hospital Not yet recruiting
The Hague, Netherlands
Contact: Jan Nicolai, Dr.            
UMC Utrecht Not yet recruiting
Utrecht, Netherlands
Contact: Karel van Erpecum, Dr.            
Sponsors and Collaborators
Leiden University Medical Center
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
UMC Utrecht
Free University Medical Center
Erasmus Medical Center
Haga Hospital
Medical Center Haaglanden
Universitaire Ziekenhuizen Leuven
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: June 12, 2012
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:
Esophageal Diseases
Esophageal and Gastric Varices
Hemorrhage
Liver Cirrhosis
Fibrosis
Varicose Veins
Gastrointestinal Hemorrhage
Gastrointestinal Diseases
Digestive System Diseases
Hypertension, Portal
Liver Diseases
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
 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 May 23, 2013