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

Juan A. Arnaiz

Status and phase: Completed; Phase 3

Conditions: Hypertension, Portal; Cirrhosis; Portal Vein Thrombosis; Bleeding Esophageal Varices

Treatments: Drug: Simvastatin; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01095185

BLEPS

2009-016500-24 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 150 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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150 participants in 2 patient groups, including a placebo group

Standard therapy + Simvastatin

Experimental group

Description:

* 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)

Treatment:

Drug: Simvastatin

Standard therapy + placebo

Placebo Comparator group

Description:

* Standard therapy: Endoscopic variceal ligation (EVL)+ B Blockers (Propanolol titrated maximum tolerated dose). * Placebo

Treatment:

Drug: Placebo