Hepatic Venous Pressure Gradient-guided Versus Standard Beta-blocker Therapy in Primary Prevention of Variceal Bleeding (Porthos)
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.
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:
- Occurrence of other cirrhosis-related complications
- Occurrence of hepatocellular carcinoma
- Costs of treatments
- Adverse effects
|Acute Bleeding Esophageal Varices Liver Cirrhosis||Procedure: Hepatic venous pressure gradient measurement||Phase 3|
|Study Design:||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|
- First variceal bleeding episodes [ Time Frame: two years of follow-up ]
- Mortality [ Time Frame: two years ]
- Occurrence of other cirrhosis-related complications [ Time Frame: two years ]ascites spontaneous bacterial peritonitis hepatic encephalopathy hepatorenal syndrome hepatocellular carcinoma
- Costs of treatments [ Time Frame: two years ]
- Adverse effects [ Time Frame: two years ]Adverse effects associated with NSBB therapy, endoscopic band ligation, hepatic venous pressure gradient
|Study Start Date:||September 2012|
|Estimated Study Completion Date:||April 2019|
|Estimated Primary Completion Date:||December 2018 (Final data collection date for primary outcome measure)|
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.
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.
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01618890
|Contact: Minneke Coenraad, Dr.||+31-71-5269111 ext *firstname.lastname@example.org|
|Universitair Ziekenhuis Antwerpen||Recruiting|
|Antwerpen, Belgium, B-2650|
|Contact: Thomas Vanwolleghem|
|Universitaire Ziekenhuizen Leuven||Recruiting|
|Contact: Frederik Nevens, Prof. dr.|
|Academisch Medisch Centrum||Recruiting|
|Contact: Ulrich Beuers, Prof.dr.|
|Free University Medical Centre||Recruiting|
|Contact: Karin van Nieuwkerk, Dr.|
|Leiden University Medical Centre||Recruiting|
|Leiden, Netherlands, 2333 ZA|
|Contact: Minneke Coenraad, Dr. +31-71-5269111 ext 99127 email@example.com|
|The Hague, Netherlands|
|Contact: Jan Nicolaï, Dr.|
|Principal Investigator:||Minneke Coenraad, Dr.||Leiden University Medical Centre|