Efficacy and Safety of Simvastatin in the Treatment of Portal Hypertension

Cirrhosis Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00594191
• Other study ID #: SIMV-HTP2003
• Secondary ID: AEM 03-0434
• Status: Completed
• Phase: Phase 2
• First received: January 3, 2008
• Last updated: January 3, 2008
• Start date: March 2004
• Est. completion date: November 2007

Study information

• Verified date: January 2008
• Source: Hospital Clinic of Barcelona
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: November 2007
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cirrhosis
• Hypertension
• Hypertension, Portal
• Liver Cirrhosis
• Portal Hypertension

Intervention

Drug:
• Simvastatin
20 mg/day p.o., increased to 40 mg/day at day 15 if no safety end-point was met
• Placebo
Placebo with the same characteristics of the drug and at the same dose

Locations

Country	Name	City	State
Spain	Hepatic Hemodynamic Laboratory. Liver Unit. Hospital Clinic.	Barcelona
Spain	Servicio de Gastroenterología, Hospital Ramón y Cajal	Madrid
Spain	Servicio de Gastroenterología, Hospital Universitario General Gregorio Marañón	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Clinic of Barcelona

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in hepatic venous pressure gradient (HVPG)		4 weeks	No
Secondary	Changes in systemic hemodynamics		4 weeks	Yes
Secondary	Changes in liver function tests		4 weeks	Yes