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Study About Simvastatin in Portal Hypertension in Compensated Cirrhosis (SIMPRO)

This study is not yet open for participant recruitment.
Verified January 2011 by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Sponsor:
Collaborator:
Instituto de Salud Carlos III
Information provided by:
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
ClinicalTrials.gov Identifier:
NCT01282398
First received: January 21, 2011
Last updated: January 24, 2011
Last verified: January 2011
History of Changes
  Purpose

The purpose of this study is to determine whether simvastatin is effective in the prevention of progression of porta hypertension in compensated cirrhosis patients.


Condition Intervention Phase
Portal Hypertension.
Liver Cirrhosis
 Drug: Simvastatin
Drug: placebo
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Prevention of Progression of Portal Hypertension in Compensated Cirrhosis Using Selective Hepatic Vasodilators. A Double-blind, Multicenter,Randomized Controlled Trial

Resource links provided by NLM:

Drug Information available for: Simvastatin
U.S. FDA Resources

Further study details as provided by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau:

Primary Outcome Measures:
  • the treatment of portal hypertension with simvastatin may prevent progression of portal hypertension [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    The main objective is to assess whether, in patients with compensated cirrhosis and mild portal hypertension (GPP between 6 and 10mmHg), the treatment of portal hypertension with simvastatin may prevent progression of portal hypertension and prevent the development of clinically significant HTP (defined GPP by a ≥ 10 mmHg)


Secondary Outcome Measures:
  • Portal hypertension complications [ Time Frame: four years ] [ Designated as safety issue: Yes ]
    Development of complications related to portal hypertension (gastrointestinal bleeding related to portal hypertension, ascites, hepatic encephalopathy).

  • Adverse effects [ Time Frame: four years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 80
Study Start Date: April 2011
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: simvastatin
The experimental group will take simvastatin 40mg for at least two years.
 Drug: Simvastatin
The experimental group will take 40 mg each 24 hours for at least two years.
Placebo Comparator: placebo
the control group wiil take placebo pills for at least two years.
 Drug: placebo
the control group wiil take placebo pills for at least two years.

Detailed Description:

Decompensation of cirrhosis is associated with a dramatic reduction of survival. Progression of portal hypertension (PHT) is the main determinant of decompensation that appears when portal pressure gradient (PPG) is ≥10mmHg (clinically significant HTP). 40% of compensated cirrhotic patients have mild PHT. However, with progression of disease 41% develop clinically significant PHT. In cirrhosis, PHT results from increased resistance to blood flow, with a dynamic component due to decreased nitric oxide (NO) bioavailability. In advanced disease increased portal venous inflow also contributes to PHT. Beta-blockers have not been useful in compensated cirrhosis with mild PHT. In early cirrhosis, vasodilators may be more adequate. Statins, drugs that inhibit the activity of HMG-CoA reductase, induce selective hepatic vasodilation due to an enhanced bioavailability of NO. Acutely, they decreases hepatic resistance, while with long-term use statins decreases PPG without deleterious effects on systemic circulation. This multicenter, randomized, double-blind placebo-controlled study is aimed at assessing whether treatment with simvastatin may prevent progression of mild PHT (with PPG between 6 and 10 mmHg) to clinically significant PHT. Patients with compensated cirrhosis, without previous decompensation, without esophageal varices at risk and with PPG between 6 and 10 mmHg will be included. The calculated sample size is 80 patients and the duration of the study 4 years (2 years including and a follow-up of at least 2 year).

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Liver cirrhosis diagnosed by previous biopsy or by clinical, laboratory, ultrasound
  • Portal hypertension gradient between6 mmHg and10 mmHg
  • Absence of esophageal and gastric varices or small esophageal varices without red signs
  • Absence previous episodes of gastrointestinal hemorrhage, ascites, encephalopathy or jaundice
  • Written informed consent

Exclusion Criteria:

  • Age <18 and> 80 years,
  • Presence or history of ascites, clinical or ultrasound,
  • Previous decompensation of liver cirrhosis, ascites or SBP, bleeding varices, large varices, hepatic encephalopathy, jaundice,
  • Thrombosis splenoportal,
  • Hepatocellular carcinoma;
  • Child-Pugh >7 point
  • Any comorbidity that leads to a restriction therapy and / or a life expectancy <12 months
  • Absolute contraindication to treatment with statins or allergy Simvastatin;
  • Concomitant potent CYP3A4 inhibitors (eg., itraconazole, ketoconazole, protease inhibitors, HIV, erythromycin, clarithromycin, telithromycin and nefazodone),
  • Pretreatment (<1 month) with simvastatin or other lipid-lowering,
  • Previous episodes of rhabdomyolysis,
  • Active alcoholic hepatitis,
  • Refusal to participate in the study or the informed consent claim;
  • Pre-treatment with beta blockers or nitrates, or endoscopic treatment for varicose veins or portosystemic derivations;
  • Pregnancy and lactation.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01282398

Contacts
Contact: Candido Villanueva, PHD 935565917 cvillanueva@santpau.cat
Contact: Angela Puente, MD 935565917 apuentesa@santpau.cat

Locations
Spain
Hospital de la Santa Creu i Sant Pau Not yet recruiting
Barcelona, Spain, 08025
Principal Investigator: Candido Villanueva, mPHD            
Sub-Investigator: Angela Puente, PHD            
Sponsors and Collaborators
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Instituto de Salud Carlos III
Investigators
Principal Investigator: Candido Villanueva, MD Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
  More Information

Publications:

Responsible Party: Candido Villanueva, Hospital de la Santa Creu i Sant Pau
ClinicalTrials.gov Identifier: NCT01282398     History of Changes
Other Study ID Numbers: IIBSP-SIM-2010-06
Study First Received: January 21, 2011
Last Updated: January 24, 2011
Health Authority: Spain: Spanish Agency of Medicines

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

ClinicalTrials.gov processed this record on June 18, 2013