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

Sponsor

Juan A. Arnaiz (Other)

Overall Status

Completed

CT.gov ID

NCT01095185

Collaborator

(none)

150

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Cirrhosis Hypertension, Portal Bleeding Esophageal Varices Portal Vein Thrombosis	Drug: Simvastatin Drug: Placebo	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Study Start Date :

Nov 1, 2010

Actual Primary Completion Date :

Sep 1, 2013

Actual Study Completion Date :

Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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)	Drug: Simvastatin Simvastatin 20 mg for 15 days, then 40 mg until the end of the study. Other Names: Simvastatina Simvastatina Ratiopharm
Placebo Comparator: Standard therapy + placebo Standard therapy: Endoscopic variceal ligation (EVL)+ B Blockers (Propanolol titrated maximum tolerated dose). Placebo	Drug: Placebo Simvastatin placebo

Arm

Intervention/Treatment

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)

Drug: Simvastatin

Simvastatin 20 mg for 15 days, then 40 mg until the end of the study.

Other Names:

Simvastatina

Simvastatina Ratiopharm

Placebo Comparator: Standard therapy + placebo

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

Drug: Placebo

Simvastatin placebo

Outcome Measures

Primary Outcome Measures

Recurrence of variceal bleeding and patient survival [12 months]

Secondary Outcome Measures

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]
Need for alternative treatments (transjugular intrahepatic portosystemic shunt [TIPS], surgery) [12 months]
Incidence of adverse events of statin treatment [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Complejo Universitario Central de Asturias	Oviedo	Asturias	Spain
2	Hospital Universitari Bellvitge	L´Hospitalet del LLobregat	Barcelona	Spain
3	Corporació Sanitària Parc Tauli	Sabadell	Barcelona	Spain
4	Hospital Arnau de Vilanova	LLeida	Catalunya	Spain
5	Complejo Hospitalario Pontevedra	Pontevedra	Galicia	Spain
6	Hospital Puerta del Hierro	Majadahonda	Madrid	Spain
7	Hospital Universitario de Alicante	Alicante		Spain
8	Hospital Clinic	Barcelona		Spain	08005
9	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain	08041
10	Hospital German Trias i Pujol	Barcelona		Spain	089016
11	Hospital de la Vall d'Hebron	Barcelona		Spain
12	Hospital Universitario del Mar	Barcelona		Spain
13	Hospital Gregorio Marañon	Madrid		Spain
14	Hospital Ramón y Cajal	Madrid		Spain
15	Hospital Universitario de Canarias	Tenerife		Spain