CirrhosisPhase 3NCT01095185
Efficacy of Statin Association With Standard Treatment in Prevention of Recurrent Hemorrhage in Patient With Cirrhosis and Variceal Bleeding
A Phase 3 study testing Simvastatin in people with Cirrhosis and Hypertension, Portal, run by Juan A. Arnaiz at 15 sites in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cirrhosis, Hypertension, Portal, Bleeding Esophageal Varices
- What is being tested?
- Simvastatin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 15 sitesSpain
- Study dates
- Nov 2010to Sep 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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,
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- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
Spain15 sites
Hospital Universitario de Alicante
Alicante, Alicante
Hospital Clinic
Barcelona, Barcelona, 08005
Hospital de la Santa Creu i Sant Pau
Barcelona, Barcelona, 08041
Hospital German Trias i Pujol
Barcelona, Barcelona, 089016
Hospital de la Vall d'Hebron
Barcelona, Barcelona
Hospital Universitario del Mar
Barcelona, Barcelona
Hospital Universitari Bellvitge
L´Hospitalet Del LLobregat, Barcelona
Hospital Arnau de Vilanova
Lleida, Catalonia
Hospital Gregorio Marañon
Madrid, Madrid
Hospital Ramón y Cajal
Madrid, Madrid
Hospital Puerta del Hierro
Majadahonda, Madrid
Complejo Universitario Central de Asturias
Oviedo, Principality of Asturias
Complejo Hospitalario Pontevedra
Pontevedra, Galicia
Corporació Sanitària Parc Tauli
Sabadell, Barcelona
Hospital Universitario de Canarias
Santa Cruz de Tenerife, Tenerife
About this study
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
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).
Read the 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.
- Being tested
- Simvastatin, Placebo
- Medical subject headings
- Fibrosis, Hypertension, Portal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SimvastatinDrug
Also called Simvastatina, Simvastatina Ratiopharm
Simvastatin 20 mg for 15 days, then 40 mg until the end of the study.
PlaceboDrug
Simvastatin placebo
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: Simvastatin |
| Standard therapy + placebo | Placebo comparator | * Standard therapy: Endoscopic variceal ligation (EVL)+ B Blockers (Propanolol titrated maximum tolerated dose).
* Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence of variceal bleeding and patient survival
Measured: 12 months
Secondary outcomes (5)
Bleeding severity in both arms.
Measured: 12 months
Appearance or progression of Portal Hypertension complications
Measured: 12 months
Appearance or progression of Portal Vein Thrombosis
Measured: 12 months
Need for alternative treatments (transjugular intrahepatic portosystemic shunt [TIPS], surgery)
Measured: 12 months
Incidence of adverse events of statin treatment
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2010 (estimated)
- Study startNov 2010
- Primary completionSep 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Juan A. Arnaiz
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Juan A. Arnaiz, Hospital Clinic of Barcelona
- Investigators
- Jaume Bosch, MD, Principal investigator, Hospital Clínic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01095185
- Sponsor's protocol ID
- BLEPS
- Other IDs
- 2009-016500-24, 2009
- Status last verified
- Mar 2015
- First submitted
- 29 Mar 2010
- Last updated
- 19 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 26774179
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01095185
- Acronym / sponsor ID
- BLEPS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Juan A. ArnaizUniversity, hospital or other
- Study start
- Nov 2010
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 30 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard therapy + Simvastatin | Experimental | Drug: 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) |
| Standard therapy + placebo | Placebo comparator | Drug: Placebo* Standard therapy: Endoscopic variceal ligation (EVL)+ B Blockers (Propanolol titrated maximum tolerated dose). * Placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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).
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SimvastatinAlso: Simvastatina, Simvastatina RatiopharmSimvastatin 20 mg for 15 days, then 40 mg until the end of the study. | Drug | Standard therapy + Simvastatin |
| PlaceboSimvastatin placebo | Drug | Standard therapy + placebo |
Primary outcome
Recurrence of variceal bleeding and patient survival
Time frame: 12 months
5 secondary outcomes
Bleeding severity in both arms.
Time frame: 12 months
Appearance or progression of Portal Hypertension complications
Time frame: 12 months
Appearance or progression of Portal Vein Thrombosis
Time frame: 12 months
Need for alternative treatments (transjugular intrahepatic portosystemic shunt [TIPS], surgery)
Time frame: 12 months
Incidence of adverse events of statin treatment
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2015.
- Derived from this study: PubMed 26774179Abraldes 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jaume Bosch, MD principal investigator
Hospital Clínic
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Simvastatin in people with Cirrhosis and Hypertension, Portal, run by Juan A. Arnaiz at 15 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence of variceal bleeding and patient survival (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01095185, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Mar 2015.