Efficacy and Safety of Simvastatin in the Treatment of Portal Hypertension - Full Text View

Sponsored by:	Hospital Clinic of Barcelona
Information provided by:	Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier:	NCT00594191

Purpose

The purpose of this study is to evaluate the effects of continuous simvastatin administration on the hepatic venous pressure gradient (HVPG), as a surrogate marker of prognosis, and its safety in patients with cirrhosis and portal hypertension.

Condition	Intervention	Phase
Cirrhosis Portal Hypertension	Drug: Simvastatin Drug: Placebo	Phase II

MedlinePlus related topics: Cirrhosis High Blood Pressure Statins

Drug Information available for: Simvastatin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Phase IV-II Randomized, Multicenter, Placebo-Controlled Double-Blind Clinical Trial Evaluating the Effects of Continuous Simvastatin Administration on Hepatic and Systemic Hemodynamics in Patients With Cirrhosis.

Further study details as provided by Hospital Clinic of Barcelona:

Primary Outcome Measures:

Changes in hepatic venous pressure gradient (HVPG) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Changes in systemic hemodynamics [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
Changes in liver function tests [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]

Enrollment:	59
Study Start Date:	March 2004
Study Completion Date:	November 2007
Primary Completion Date:	April 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Placebo Comparator Placebo treatment	Drug: Placebo Placebo with the same characteristics of the drug and at the same dose
B: Experimental	Drug: Simvastatin 20 mg/day p.o., increased to 40 mg/day at day 15 if no safety end-point was met

Detailed Description:

Statins exert beneficial vascular effects independently of cholesterol reduction by improving endothelial dysfunction. In cirrhosis sinusoidal endothelial dysfunction further increases intrahepatic resistance and portal pressure. Previous studies have shown that statins improve hepatic endothelial dysfunction in cirrhosis, suggesting that statins could be an effective therapy for portal hypertension (PHT). This randomized controlled trial evaluated the effects of continuous simvastatin administration on the hepatic venous pressure gradient (HVPG), as a surrogate marker of prognosis, and its safety in patients with cirrhosis and PHT.

Eligibility

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

Criteria

Inclusion Criteria:

Age between 18 and 75.
Clinical, analytical, ultrasound or pathological criteria of cirrhosis.
Severe sinusoidal portal hypertension (HVPG >12 mmHg)
Signed informed consent

Exclusion Criteria:

Pregnancy or lactation
Advanced liver disease defined as one of the following: Prothrombin rate <40%, Bilirubin >5 mg/dl, hepatic encephalopathy > grade I or Child-Pugh score >12).
Portal vein thrombosis
Multinodular hepatocellular carcinoma or single hepatocellular carcinoma > 5 cm.
Heart, renal or respiratory failure
Previous portal-systemic shunt
Treatment with organic nitrates
Hypersensitivity to HMG-CoA reductase inhibitors
Previous treatment with HMG-CoA reductase inhibitors
Treatment with calcium channel blockers

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00594191

Locations

Spain
Hepatic Hemodynamic Laboratory. Liver Unit. Hospital Clinic.
Barcelona, Spain, 08036
Servicio de Gastroenterología, Hospital Ramón y Cajal
Madrid, Spain, 28871
Servicio de Gastroenterología, Hospital Universitario General Gregorio Marañón
Madrid, Spain

Sponsors and Collaborators

Hospital Clinic of Barcelona

Investigators

Principal Investigator:

Jaime Bosch, MD

Hospital Clinic. Barcelona

More Information

Responsible Party:	University of Barcelona ( Jaime Bosch /Professor of Medicine )
Study ID Numbers:	SIMV-HTP2003, AEM 03-0434
Study First Received:	January 3, 2008
Last Updated:	January 3, 2008
ClinicalTrials.gov Identifier:	NCT00594191
Health Authority:	Spain: Spanish Agency of Medicines

Keywords provided by Hospital Clinic of Barcelona:

Statins
HMG-CoA reductase inhibitors
Cirrhosis
Portal hypertension
Variceal bleeding

Study placed in the following topic categories:

Liver Diseases
Digestive System Diseases
Simvastatin
Fibrosis
Vascular Diseases

Hypertension, Portal
Liver Cirrhosis
Hemorrhage
Portal hypertension
Hypertension

Additional relevant MeSH terms:

Antimetabolites
Pathologic Processes
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Antilipemic Agents

Enzyme Inhibitors
Cardiovascular Diseases
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009