Efficacy and Safety of Simvastatin in the Treatment of Portal Hypertension

Phase 2

Completed

• Conditions: Cirrhosis; Portal Hypertension
• Interventions: Drug: Placebo; Drug: Simvastatin

• Registration Number: NCT00594191
• Lead Sponsor: Hospital Clinic of Barcelona

Brief Summary

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.

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.

Study Timeline

• Study Start: 2004-03
• Primary Completion: 2007-04
• Study Completion: 2007-11
• Status Verified: 2008-01
• Study First Submitted: 2008-01-03
• Study First Submitted QC: 2008-01-03
• Last Update Submitted: 2008-01-03
• Study First Posted: 2008-01-15
• Last Update Posted: 2008-01-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 59

Inclusion Criteria

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

Exclusion Criteria

1. Pregnancy or lactation
2. 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).
3. Portal vein thrombosis
4. Multinodular hepatocellular carcinoma or single hepatocellular carcinoma > 5 cm.
5. Heart, renal or respiratory failure
6. Previous portal-systemic shunt
7. Treatment with organic nitrates
8. Hypersensitivity to HMG-CoA reductase inhibitors
9. Previous treatment with HMG-CoA reductase inhibitors
10. Treatment with calcium channel blockers

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	Placebo	Placebo treatment
B	Simvastatin	-

Primary Outcome Measures

Name	Time	Method
Changes in hepatic venous pressure gradient (HVPG)	4 weeks

Secondary Outcome Measures

Name	Time	Method
Changes in systemic hemodynamics	4 weeks
Changes in liver function tests	4 weeks

Trial Locations

Locations (3)

Servicio de Gastroenterología, Hospital Ramón y Cajal; 🇪🇸 Madrid, Spain

Hepatic Hemodynamic Laboratory. Liver Unit. Hospital Clinic.; 🇪🇸 Barcelona, Spain

Servicio de Gastroenterología, Hospital Universitario General Gregorio Marañón; 🇪🇸 Madrid, Spain