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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Hospital Clinic of Barcelona
Sponsor:
Information provided by (Responsible Party):
Juan A. Arnaiz, Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier:
NCT01095185
First received: March 29, 2010
Last updated: February 21, 2013
Last verified: February 2013
  Purpose

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 Intervention Phase
Cirrhosis
Hypertension, Portal
Variceal Bleeding
Portal Vein Thrombosis
Drug: Simvastatin
Drug: Placebo
Phase 3

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: 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

Resource links provided by NLM:


Further study details as provided by Hospital Clinic of Barcelona:

Primary Outcome Measures:
  • Recurrence of variceal bleeding and patient survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Bleeding severity in both arms. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Appearance or progression of Portal Hypertension complications [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Appearance or progression of Portal Vein Thrombosis [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Need for alternative treatments (transjugular intrahepatic portosystemic shunt [TIPS], surgery) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Incidence of adverse events of statin treatment [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 158
Study Start Date: November 2010
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

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

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).
  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: NCT01095185

Contacts
Contact: Judit Pich 932275400 ext 2815 jpich@clinic.ub.es

Locations
Spain
Complejo Universitario Central de Asturias Not yet recruiting
Oviedo, Asturias, Spain
Hospital Universitari Bellvitge Not yet recruiting
L´Hospitalet del LLobregat, Barcelona, Spain
Corporació Sanitària Parc Tauli Not yet recruiting
Sabadell, Barcelona, Spain
Hospital Arnau de Vilanova Not yet recruiting
LLeida, Catalunya, Spain
Complejo Hospitalario Pontevedra Not yet recruiting
Pontevedra, Galicia, Spain
Hospital Puerta del Hierro Not yet recruiting
Majadahonda, Madrid, Spain
Hospital Universitario de Alicante Not yet recruiting
Alicante, Spain
Hospital de la Santa Creu i Sant Pau Not yet recruiting
Barcelona, Spain, 08041
Contact: Càndid Villanueva, MD       cvillanueva@santpau.cat   
Hospital Clinic Recruiting
Barcelona, Spain, 08005
Contact: Jaume Bosch Genover, MD    93 227 5400 ext 2057    Jbosch@clinic.ub.es   
Principal Investigator: Jaume Bosch Genover, MD         
Sub-Investigator: Juan Gonzalez Abraldes, MD         
Hospital German Trias i Pujol Recruiting
Barcelona, Spain, 089016
Contact: Ramón Planas         
Hospital de la Vall d'Hebron Recruiting
Barcelona, Spain
Hospital Universitario del Mar Not yet recruiting
Barcelona, Spain
Hospital Gregorio Marañon Not yet recruiting
Madrid, Spain
Hospital Ramón y Cajal Not yet recruiting
Madrid, Spain
Hospital Universitario de Canarias Not yet recruiting
Tenerife, Spain
Sponsors and Collaborators
Juan A. Arnaiz
  More Information

No publications provided

Responsible Party: Juan A. Arnaiz, Clinical Research Manager, Hospital Clinic of Barcelona
ClinicalTrials.gov Identifier: NCT01095185     History of Changes
Other Study ID Numbers: BLEPS
Study First Received: March 29, 2010
Last Updated: February 21, 2013
Health Authority: Spain: Spanish Agency of Medicines

Additional relevant MeSH terms:
Hemorrhage
Hypertension
Hypertension, Portal
Liver Cirrhosis
Fibrosis
Thrombosis
Venous Thrombosis
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Liver Diseases
Digestive System Diseases
Embolism and Thrombosis
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 July 23, 2014