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.
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

March 29, 2010
February 21, 2013
November 2010
July 2013   (final data collection date for primary outcome measure)
Recurrence of variceal bleeding and patient survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01095185 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 (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 ]
Not Provided
Not Provided
 
Efficacy of Statin Association With Standard Treatment in Prevention of Recurrent Hemorrhage in Patient With Cirrhosis and Variceal Bleeding
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

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).

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Cirrhosis
  • Hypertension, Portal
  • Variceal Bleeding
  • Portal Vein Thrombosis
  • 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
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
158
July 2013
July 2013   (final data collection date for primary outcome measure)

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).
Both
18 Years to 80 Years
No
Contact: Judit Pich 932275400 ext 2815 jpich@clinic.ub.es
Spain
 
NCT01095185
BLEPS
No
Juan A. Arnaiz, Hospital Clinic of Barcelona
Juan A. Arnaiz
Not Provided
Not Provided
Hospital Clinic of Barcelona
February 2013

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