Efficacy and Safety of Simvastatin in the Treatment of Portal Hypertension

This study has been completed.
Sponsor:
Information provided by:
Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier:
NCT00594191
First received: January 3, 2008
Last updated: NA
Last verified: January 2008
History: No changes posted
  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 2

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

Resource links provided by NLM:


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
Placebo Comparator: A
Placebo treatment
Drug: Placebo
Placebo with the same characteristics of the drug and at the same dose
Experimental: B 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:

  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 of Barcelona
  More Information

No publications provided

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

Keywords provided by Hospital Clinic of Barcelona:
Statins
HMG-CoA reductase inhibitors
Cirrhosis
Portal hypertension
Variceal bleeding

Additional relevant MeSH terms:
Hypertension
Liver Cirrhosis
Hypertension, Portal
Vascular Diseases
Cardiovascular Diseases
Liver Diseases
Digestive System Diseases
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014