Clinical trial NCT01095185: Efficacy of Statin Association With Standard Treatment in Prevention of Recurrent Hemorrhage in Patient With Cirrhosis and Variceal Bleeding
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cirrhosis
Hypertension, Portal
Bleeding Esophageal Varices
Portal Vein Thrombosis
Lead sponsor: Hospital Clinic of Barcelona
Sponsor class: OTHER
First posted: 2010-03-30
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Recurrence of variceal bleeding and patient survival
timeFrame: 12 months
Secondary outcomes:
measure: Bleeding severity in both arms.
timeFrame: 12 months
measure: Appearance or progression of Portal Hypertension complications
timeFrame: 12 months
measure: Appearance or progression of Portal Vein Thrombosis
timeFrame: 12 months
measure: Need for alternative treatments (transjugular intrahepatic portosystemic shunt [TIPS], surgery)
timeFrame: 12 months
measure: Incidence of adverse events of statin treatment
timeFrame: 12 months
Other outcomes:
Locations:
city: Oviedo
country: Spain
facility: Complejo Universitario Central de Asturias
state: Asturias
city: L´Hospitalet del LLobregat
country: Spain
facility: Hospital Universitari Bellvitge
state: Barcelona
city: Sabadell
country: Spain
facility: Corporació Sanitària Parc Tauli
state: Barcelona
city: LLeida
country: Spain
facility: Hospital Arnau de Vilanova
state: Catalunya
city: Pontevedra
country: Spain
facility: Complejo Hospitalario Pontevedra
state: Galicia
city: Majadahonda
country: Spain
facility: Hospital Puerta del Hierro
state: Madrid
city: Alicante
country: Spain
facility: Hospital Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Clinic
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital German Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital de la Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Universitario del Mar
city: Madrid
country: Spain
facility: Hospital Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Tenerife
country: Spain
facility: Hospital Universitario de Canarias
Study officials:
affiliation: Hospital Clínic
name: Jaume Bosch, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Abraldes JG, Villanueva C, Aracil C, Turnes J, Hernandez-Guerra M, Genesca J, Rodriguez M, Castellote J, Garcia-Pagan JC, Torres F, Calleja JL, Albillos A, Bosch J; BLEPS Study Group. Addition of Simvastatin to Standard Therapy for the Prevention of Variceal Rebleeding Does Not Reduce Rebleeding but Increases Survival in Patients With Cirrhosis. Gastroenterology. 2016 May;150(5):1160-1170.e3. doi: 10.1053/j.gastro.2016.01.004. Epub 2016 Jan 14.