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Efficacy of Statin Association With Standard Treatment in Prevention of Recurrent Hemorrhage in Patient With Cirrhosis and Variceal Bleeding

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01095185
Recruitment Status : Completed
First Posted : March 30, 2010
Last Update Posted : March 19, 2015
Information provided by (Responsible Party):
Juan A. Arnaiz, Hospital Clinic of Barcelona

Brief Summary:

This is a prospective, double blind controlled trial in which patients with esophagic variceal bleeding treated with standard therapy (endoscopic variceal ligation(EVL) + B-blockers), will be randomized to receive statins or placebo. They will be followed up during 12 months to determinate whether statins are effective in prevention of variceal bleeding recurrence and evaluate patient survival.

Randomization will be stratified according to the degree of hepatic insufficiency, assessed by the Child-Pugh classifications (A,B or C).

Condition or disease Intervention/treatment Phase
Cirrhosis Hypertension, Portal Bleeding Esophageal Varices Portal Vein Thrombosis Drug: Simvastatin Drug: Placebo Phase 3

Detailed Description:

A mayor cause of cirrhosis-related morbility and mortality is the development of variceal hemorrhage, a direct consequence of portal hypertension. In addition, survivors of an episode of active bleeding have a 70 % risk of recurrent hemorrhage within two years of the bleeding episode and the highest risk it is situated in the first six weeks after the hemorrhage episode.

The recommended treatment in AASLD guidelines is the combination of non selective Betablockers with endoscopic treatment with EVL, with high recurrence (30% in 2 years).

The hypothesis of this study is that statins are candidates for improving portal hypertension treatment in patients with cirrhosis, improving vascular function as well as preventing venous thrombotic events.

Patients with liver cirrhosis and variceal bleeding with standard treatment will be stratified and after randomized to undergo either statins (20 mg for 15 days, and after 40 mg/day) or placebo. They will be followed up for 12 months.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Multicenter,Double Blind,Controlled With Placebo Trial About Efficacy of Statin Association With Standard Treatment in Prevention of Recurrent Hemorrhage in Patient With Liver Cirrhosis and Variceal Bleeding
Study Start Date : November 2010
Actual Primary Completion Date : September 2013
Actual Study Completion Date : September 2013

Arm Intervention/treatment
Experimental: Standard therapy + Simvastatin
  • Standard therapy: Endoscopic variceal ligation (EVL)+ B Blockers (Propanolol titrated until achieve maximum tolerated dose)
  • Simvastatin (20 mg for 15 days and after 40 mg/day until the end of the study)
Drug: Simvastatin
Simvastatin 20 mg for 15 days, then 40 mg until the end of the study.
Other Names:
  • Simvastatina
  • Simvastatina Ratiopharm

Placebo Comparator: Standard therapy + placebo
  • Standard therapy: Endoscopic variceal ligation (EVL)+ B Blockers (Propanolol titrated maximum tolerated dose).
  • Placebo
Drug: Placebo
Simvastatin placebo

Primary Outcome Measures :
  1. Recurrence of variceal bleeding and patient survival [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Bleeding severity in both arms. [ Time Frame: 12 months ]
  2. Appearance or progression of Portal Hypertension complications [ Time Frame: 12 months ]
  3. Appearance or progression of Portal Vein Thrombosis [ Time Frame: 12 months ]
  4. Need for alternative treatments (transjugular intrahepatic portosystemic shunt [TIPS], surgery) [ Time Frame: 12 months ]
  5. Incidence of adverse events of statin treatment [ Time Frame: 12 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients between 18 and 80 years old.
  • Clinical criteria and/or analytical, ultrasound and/or liver biopsy consistent with the diagnosis of liver cirrhosis.
  • Hematemesis or melenas within 7 days prior to study inclusion.
  • Variceal bleeding. Endoscopic diagnosis:

    • Active variceal bleeding.
    • Clot or platelet cluster or,
    • Esophageal varices associated to red blood in esophagogastric lumen in the absence of other sources of bleeding.
  • Patients with standard treatment for prevention of recurrence of variceal bleeding (EVL+B Blockers,Propanolol).
  • Women of childbearing age should have a urine pregnancy test negative for 7 days before commencement of treatment and postmenopausal women must have amenorrhea for at least 12 months to be considered not fertile. Potential childbearing women and men must commit to use adequate contraception prior to joining the study and during it.
  • Written informed consent to participate in the study.

Exclusion Criteria:

  • Pregnancy or lactation
  • Presence multiple hepatocellular carcinoma or only diameter> 5 cm.
  • Renal failure ( Creatinine > 2 mg/dl)
  • Advanced liver disfunction (Child Pugh > 13 points)
  • Contraindication for statins.
  • Patients HIV treated with antiretroviral therapy.
  • Pre-treatment with portosystemic shunt ( surgical or percutaneous).
  • Bleeding due to gastric varices.
  • Patients with total portal vein thrombosis or portal cavernomatosis.
  • Patients previously treated with endoscopic variceal ligation and B- Blockers (before index episode).
  • Patients previously treated with statins ( one month before the study).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01095185

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Complejo Universitario Central de Asturias
Oviedo, Asturias, Spain
Hospital Universitari Bellvitge
L´Hospitalet del LLobregat, Barcelona, Spain
Corporació Sanitària Parc Tauli
Sabadell, Barcelona, Spain
Hospital Arnau de Vilanova
LLeida, Catalunya, Spain
Complejo Hospitalario Pontevedra
Pontevedra, Galicia, Spain
Hospital Puerta del Hierro
Majadahonda, Madrid, Spain
Hospital Universitario de Alicante
Alicante, Spain
Hospital Clinic
Barcelona, Spain, 08005
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain, 08041
Hospital German Trias i Pujol
Barcelona, Spain, 089016
Hospital de la Vall d'Hebron
Barcelona, Spain
Hospital Universitario del Mar
Barcelona, Spain
Hospital Gregorio Marañon
Madrid, Spain
Hospital Ramón y Cajal
Madrid, Spain
Hospital Universitario de Canarias
Tenerife, Spain
Sponsors and Collaborators
Juan A. Arnaiz
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Principal Investigator: Jaume Bosch, MD Hospital Clínic

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Juan A. Arnaiz, Clinical Research Manager, Hospital Clinic of Barcelona Identifier: NCT01095185     History of Changes
Other Study ID Numbers: BLEPS
2009-016500-24 ( EudraCT Number )
First Posted: March 30, 2010    Key Record Dates
Last Update Posted: March 19, 2015
Last Verified: March 2015
Additional relevant MeSH terms:
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Liver Cirrhosis
Esophageal and Gastric Varices
Hypertension, Portal
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Liver Diseases
Digestive System Diseases
Embolism and Thrombosis
Esophageal Diseases
Gastrointestinal Diseases
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors