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

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ClinicalTrials.gov Identifier: NCT01095185
Recruitment Status : Completed
First Posted : March 30, 2010
Last Update Posted : March 19, 2015
Sponsor:
Information provided by (Responsible Party):
Juan A. Arnaiz, Hospital Clinic of Barcelona

Tracking Information
First Submitted Date  ICMJE March 29, 2010
First Posted Date  ICMJE March 30, 2010
Last Update Posted Date March 19, 2015
Study Start Date  ICMJE November 2010
Actual Primary Completion Date September 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 29, 2010)
Recurrence of variceal bleeding and patient survival [ Time Frame: 12 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01095185 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 9, 2010)
  • Bleeding severity in both arms. [ Time Frame: 12 months ]
  • Appearance or progression of Portal Hypertension complications [ Time Frame: 12 months ]
  • Appearance or progression of Portal Vein Thrombosis [ Time Frame: 12 months ]
  • Need for alternative treatments (transjugular intrahepatic portosystemic shunt [TIPS], surgery) [ Time Frame: 12 months ]
  • Incidence of adverse events of statin treatment [ Time Frame: 12 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2010)
  • Bleeding severity in both arms. [ Time Frame: 12 months ]
  • Appearance or progression of Portal Hypertension complications [ Time Frame: 12 months ]
  • Appearance or progression of Portal Vein Thrombosis [ Time Frame: 12 months ]
  • Need for alternative treatments (TIPS, surgery) [ Time Frame: 12 months ]
  • Incidence of adverse events of statin treatment [ Time Frame: 12 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Statin Association With Standard Treatment in Prevention of Recurrent Hemorrhage in Patient With Cirrhosis and Variceal Bleeding
Official Title  ICMJE 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
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).

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Cirrhosis
  • Hypertension, Portal
  • Bleeding Esophageal Varices
  • Portal Vein Thrombosis
Intervention  ICMJE
  • Drug: Simvastatin
    Simvastatin 20 mg for 15 days, then 40 mg until the end of the study.
    Other Names:
    • Simvastatina
    • Simvastatina Ratiopharm
  • Drug: Placebo
    Simvastatin placebo
Study Arms  ICMJE
  • 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)
    Intervention: Drug: Simvastatin
  • Placebo Comparator: Standard therapy + placebo
    • Standard therapy: Endoscopic variceal ligation (EVL)+ B Blockers (Propanolol titrated maximum tolerated dose).
    • Placebo
    Intervention: Drug: Placebo
Publications * Abraldes JG, Villanueva C, Aracil C, Turnes J, Hernandez-Guerra M, Genesca J, Rodriguez M, Castellote J, García-Pagán JC, Torres F, Calleja JL, Albillos A, Bosch J; BLEPS Study Group. Addition of Simvastatin to Standard Therapy for the Prevention of Variceal Rebleeding Does Not Reduce Rebleeding but Increases Survival in Patients With Cirrhosis. Gastroenterology. 2016 May;150(5):1160-1170.e3. doi: 10.1053/j.gastro.2016.01.004. Epub 2016 Jan 14.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 18, 2015)
150
Original Estimated Enrollment  ICMJE
 (submitted: March 29, 2010)
158
Actual Study Completion Date  ICMJE September 2013
Actual Primary Completion Date September 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01095185
Other Study ID Numbers  ICMJE BLEPS
2009-016500-24 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Juan A. Arnaiz, Hospital Clinic of Barcelona
Study Sponsor  ICMJE Juan A. Arnaiz
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jaume Bosch, MD Hospital Clínic
PRS Account Hospital Clinic of Barcelona
Verification Date March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP