NCT01095185

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
150

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Nov 2010

Typical duration for phase_3

Geographic Reach
1 country

15 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 29, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 30, 2010

Completed
7 months until next milestone

Study Start

First participant enrolled

November 1, 2010

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2013

Completed
Last Updated

March 19, 2015

Status Verified

March 1, 2015

Enrollment Period

2.8 years

First QC Date

March 29, 2010

Last Update Submit

March 18, 2015

Conditions

CirrhosisHypertension, PortalBleeding Esophageal VaricesPortal Vein Thrombosis

Outcome Measures

Primary Outcomes (1)

  • Recurrence of variceal bleeding and patient survival

    12 months

Secondary Outcomes (5)

  • 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

Study Arms (2)

Standard therapy + Simvastatin

EXPERIMENTAL

* 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

Standard therapy + placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

SimvastatinDRUG

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

Also known as: Simvastatina, Simvastatina Ratiopharm
Standard therapy + Simvastatin
PlaceboDRUG

Simvastatin placebo

Standard therapy + placebo

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients between 18 and 80 years old.
  • Clinical criteria and/or analytical, ultrasound and/or liver biopsy consistent with the diagnosis of liver cirrhosis.
  • 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.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (15)

Hospital Universitario de Alicante

Alicante, Alicante, Spain

Location

Hospital Clinic

Barcelona, Barcelona, 08005, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Barcelona, 08041, Spain

Location

Hospital German Trias i Pujol

Barcelona, Barcelona, 089016, Spain

Location

Hospital de la Vall d'Hebron

Barcelona, Barcelona, Spain

Location

Hospital Universitario del Mar

Barcelona, Barcelona, Spain

Location

Hospital Universitari Bellvitge

L´Hospitalet Del LLobregat, Barcelona, Spain

Location

Corporació Sanitària Parc Tauli

Sabadell, Barcelona, Spain

Location

Hospital Arnau de Vilanova

Lleida, Catalonia, Spain

Location

Complejo Hospitalario Pontevedra

Pontevedra, Galicia, Spain

Location

Hospital Gregorio Marañon

Madrid, Madrid, Spain

Location

Hospital Ramón y Cajal

Madrid, Madrid, Spain

Location

Hospital Puerta del Hierro

Majadahonda, Madrid, Spain

Location

Complejo Universitario Central de Asturias

Oviedo, Principality of Asturias, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Tenerife, Spain

Location

Related Publications (1)

  • 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.

    PMID: 26774179DERIVED

MeSH Terms

Conditions

FibrosisHypertension, Portal

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Pathologic ProcessesPathological Conditions, Signs and SymptomsLiver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

LovastatinNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic Compounds

Study Officials

  • Jaume Bosch, MD

    Hospital Clínic

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Clinical Research Manager

Study Record Dates

First Submitted

March 29, 2010

First Posted

March 30, 2010

Study Start

November 1, 2010

Primary Completion

September 1, 2013

Study Completion

September 1, 2013

Last Updated

March 19, 2015

Record last verified: 2015-03

Locations

ES(15)