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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-016500-24 | EudraCT Number |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard therapy + Simvastatin | Experimental |
|
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| Standard therapy + placebo | Placebo Comparator |
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Simvastatin | Drug | Simvastatin 20 mg for 15 days, then 40 mg until the end of the study. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Recurrence of variceal bleeding and patient survival | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Bleeding severity in both arms. | 12 months | |
| Appearance or progression of Portal Hypertension complications | 12 months | |
| Appearance or progression of Portal Vein Thrombosis |
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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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Jaume Bosch, MD | Hospital Clínic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitario de Alicante | Alicante | Alicante | Spain | |||
| Hospital Clinic |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26774179 | Derived | 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. |
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| Placebo | Drug | Simvastatin placebo |
|
| 12 months |
| Need for alternative treatments (transjugular intrahepatic portosystemic shunt [TIPS], surgery) | 12 months |
| Incidence of adverse events of statin treatment | 12 months |
| Barcelona |
| Barcelona |
| 08005 |
| Spain |
| Hospital de la Santa Creu i Sant Pau | Barcelona | Barcelona | 08041 | Spain |
| Hospital German Trias i Pujol | Barcelona | Barcelona | 089016 | Spain |
| Hospital de la Vall d'Hebron | Barcelona | Barcelona | Spain |
| Hospital Universitario del Mar | Barcelona | Barcelona | Spain |
| Hospital Universitari Bellvitge | L´Hospitalet Del LLobregat | Barcelona | Spain |
| Corporació Sanitària Parc Tauli | Sabadell | Barcelona | Spain |
| Hospital Arnau de Vilanova | Lleida | Catalonia | Spain |
| Complejo Hospitalario Pontevedra | Pontevedra | Galicia | Spain |
| Hospital Gregorio Marañon | Madrid | Madrid | Spain |
| Hospital Ramón y Cajal | Madrid | Madrid | Spain |
| Hospital Puerta del Hierro | Majadahonda | Madrid | Spain |
| Complejo Universitario Central de Asturias | Oviedo | Principality of Asturias | Spain |
| Hospital Universitario de Canarias | Santa Cruz de Tenerife | Tenerife | Spain |
| ID | Term |
|---|---|
| D005355 | Fibrosis |
| D006975 | Hypertension, Portal |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D019821 | Simvastatin |
| ID | Term |
|---|---|
| D008148 | Lovastatin |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
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