Efficacy and Safety of Simvastatin in the Treatment of Portal Hypertension

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Cirrhosis, Portal Hypertension

Intervention / Treatment
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* Drug: Simvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: A<br>Placebo treatment | Drug: Placebo<br>* Placebo with the same characteristics of the drug and at the same dose<br>|
| Experimental: B<br> | Drug: Simvastatin<br>* 20 mg/day p.o., increased to 40 mg/day at day 15 if no safety end-point was met<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in hepatic venous pressure gradient (HVPG) |  | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in systemic hemodynamics |  | 4 weeks | 
| Changes in liver function tests |  | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Statins, HMG-CoA reductase inhibitors, Cirrhosis, Portal hypertension, Variceal bleeding