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

Phase 3

Completed

• Conditions: Cirrhosis; Portal Vein Thrombosis; Bleeding Esophageal Varices; Hypertension, Portal
• Interventions: Drug: Placebo; Drug: Simvastatin

• Registration Number: NCT01095185
• Lead Sponsor: Juan A. Arnaiz

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 Timeline

• Study First Submitted: 2010-03-29
• Study First Submitted QC: 2010-03-29
• Study First Posted: 2010-03-30
• Study Start: 2010-11
• Primary Completion: 2013-09
• Study Completion: 2013-09
• Status Verified: 2015-03
• Last Update Submitted: 2015-03-18
• Last Update Posted: 2015-03-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Recurrence of variceal bleeding and patient survival	12 months

Secondary Outcome Measures

Name	Time	Method
Need for alternative treatments (transjugular intrahepatic portosystemic shunt [TIPS], surgery)	12 months
Bleeding severity in both arms.	12 months
Appearance or progression of Portal Hypertension complications	12 months
Appearance or progression of Portal Vein Thrombosis	12 months
Incidence of adverse events of statin treatment	12 months

Trial Locations

Locations (15)

Hospital German Trias i Pujol; 🇪🇸 Barcelona, Spain

Corporació Sanitària Parc Tauli; 🇪🇸 Sabadell, Barcelona, Spain

Complejo Universitario Central de Asturias; 🇪🇸 Oviedo, Asturias, Spain

Hospital Arnau de Vilanova; 🇪🇸 LLeida, Catalunya, Spain

Hospital Universitari Bellvitge; 🇪🇸 L´Hospitalet del LLobregat, Barcelona, Spain

Complejo Hospitalario Pontevedra; 🇪🇸 Pontevedra, Galicia, Spain

Hospital Universitario de Alicante; 🇪🇸 Alicante, Spain

Hospital Clinic; 🇪🇸 Barcelona, Spain

Hospital de la Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Puerta del Hierro; 🇪🇸 Majadahonda, Madrid, Spain

Hospital Universitario del Mar; 🇪🇸 Barcelona, Spain

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Gregorio Marañon; 🇪🇸 Madrid, Spain

Hospital Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario de Canarias; 🇪🇸 Tenerife, Spain