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

Cirrhosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01095185
• Other study ID #: BLEPS
• Secondary ID: 2009-016500-24
• Status: Completed
• Phase: Phase 3
• First received: March 29, 2010
• Last updated: March 18, 2015
• Start date: November 2010
• Est. completion date: September 2013

Study information

• Verified date: March 2015
• Source: Hospital Clinic of Barcelona
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bleeding Esophageal Varices
• Cirrhosis
• Esophageal and Gastric Varices
• Gastrointestinal Hemorrhage
• Hemorrhage
• Hypertension, Portal
• Liver Cirrhosis
• Portal Vein Thrombosis
• Venous Thrombosis

Intervention

Drug:
• Simvastatin
Simvastatin 20 mg for 15 days, then 40 mg until the end of the study.
• Placebo
Simvastatin placebo

Locations

Country	Name	City	State
Spain	Hospital Universitario de Alicante	Alicante
Spain	Hospital Clinic	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital de la Vall d'Hebron	Barcelona
Spain	Hospital German Trias i Pujol	Barcelona
Spain	Hospital Universitario del Mar	Barcelona
Spain	Hospital Universitari Bellvitge	L´Hospitalet del LLobregat	Barcelona
Spain	Hospital Arnau de Vilanova	LLeida	Catalunya
Spain	Hospital Gregorio Marañon	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Puerta del Hierro	Majadahonda	Madrid
Spain	Complejo Universitario Central de Asturias	Oviedo	Asturias
Spain	Complejo Hospitalario Pontevedra	Pontevedra	Galicia
Spain	Corporació Sanitària Parc Tauli	Sabadell	Barcelona
Spain	Hospital Universitario de Canarias	Tenerife

Sponsors (1)

Lead Sponsor	Collaborator
Juan A. Arnaiz

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence of variceal bleeding and patient survival		12 months	No
Secondary	Bleeding severity in both arms.		12 months	No
Secondary	Appearance or progression of Portal Hypertension complications		12 months	No
Secondary	Appearance or progression of Portal Vein Thrombosis		12 months	No
Secondary	Need for alternative treatments (transjugular intrahepatic portosystemic shunt [TIPS], surgery)		12 months	No
Secondary	Incidence of adverse events of statin treatment		12 months	Yes