Clinical trial NCT00594191: Efficacy and Safety of Simvastatin in the Treatment of Portal Hypertension
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cirrhosis
Portal Hypertension
Keywords: Statins
HMG-CoA reductase inhibitors
Cirrhosis
Portal hypertension
Variceal bleeding
Lead sponsor: Hospital Clinic of Barcelona
Sponsor class: OTHER
First posted: 2008-01-15
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in hepatic venous pressure gradient (HVPG)
timeFrame: 4 weeks
Secondary outcomes:
measure: Changes in systemic hemodynamics
timeFrame: 4 weeks
measure: Changes in liver function tests
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hepatic Hemodynamic Laboratory. Liver Unit. Hospital Clinic.
city: Madrid
country: Spain
facility: Servicio de Gastroenterología, Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Servicio de Gastroenterología, Hospital Universitario General Gregorio Marañón
Study officials:
affiliation: Hospital Clinic of Barcelona
name: Jaime Bosch, MD
role: PRINCIPAL_INVESTIGATOR
References: