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

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ClinicalTrials.gov Identifier: NCT01618890
Recruitment Status : Recruiting
First Posted : June 13, 2012
Last Update Posted : June 22, 2017
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
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

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

  Show Detailed Description

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : September 2012
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : April 2019


Arms and Interventions

Arm Intervention/treatment
Experimental: HVPG-propranolol arm

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

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
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.


Outcome Measures

Primary Outcome Measures :
  1. First variceal bleeding episodes [ Time Frame: two years of follow-up ]

Secondary Outcome Measures :
  1. Mortality [ Time Frame: two years ]
  2. Occurrence of other cirrhosis-related complications [ Time Frame: two years ]
    ascites spontaneous bacterial peritonitis hepatic encephalopathy hepatorenal syndrome hepatocellular carcinoma

  3. Costs of treatments [ Time Frame: two years ]
  4. Adverse effects [ Time Frame: two years ]
    Adverse effects associated with NSBB therapy, endoscopic band ligation, hepatic venous pressure gradient


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01618890


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

Locations
Belgium
Universitair Ziekenhuis Antwerpen Recruiting
Antwerpen, Belgium, B-2650
Contact: Thomas Vanwolleghem         
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

Responsible Party: Dr. M.J.Coenraad, Dr., Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT01618890     History of Changes
Other Study ID Numbers: LUMC-40226
First Posted: June 13, 2012    Key Record Dates
Last Update Posted: June 22, 2017
Last Verified: June 2017

Keywords provided by Dr. M.J.Coenraad, 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
Propranolol
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents