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

June 11, 2012
February 6, 2014
September 2012
September 2015   (final data collection date for primary outcome measure)
First variceal bleeding episodes [ Time Frame: two years of follow-up ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01618890 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
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

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

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

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acute Bleeding Esophageal Varices
  • Liver Cirrhosis
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
  • Experimental: HVPG-propranolol arm
    Intervention: Procedure: Hepatic venous pressure gradient measurement
  • No Intervention: Propranolol arm
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
78
April 2016
September 2015   (final data collection date for primary outcome measure)

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)
Both
18 Years to 75 Years
No
Contact: Minneke Coenraad, Dr. +31-71-5269111 ext *9127 m.j.coenraad@lumc.nl
Belgium,   Netherlands
 
NCT01618890
LUMC-40226
Yes
Dr. M.J.Coenraad, Leiden University Medical Center
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)
Principal Investigator: Minneke Coenraad, Dr. Leiden University Medical Centre
Leiden University Medical Center
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP