Portal Hypertension.Phase 4SIMPRONCT01282398
Study About Simvastatin in Portal Hypertension in Compensated Cirrhosis
A Phase 4 study testing Simvastatin in people with Portal Hypertension. and Liver Cirrhosis, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site in Spain.
Trial summary
The purpose of this study is to determine whether simvastatin is effective in the prevention of progression of porta hypertension in compensated cirrhosis patients. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Portal Hypertension., Liver Cirrhosis
- What is being tested?
- Simvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteSpain
- Study dates
- Apr 2011to Apr 2015
- Phase
- Phase 4
- 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
- Liver cirrhosis diagnosed by previous biopsy or by clinical, laboratory, ultrasound
- Portal hypertension gradient between6 mmHg and10 mmHg
- Absence of esophageal and gastric varices or small esophageal varices without red signs
- Absence previous episodes of gastrointestinal hemorrhage, ascites, encephalopathy or jaundice
- Written informed consent
Who cannot join
- Age <18 and> 80 years,
- Presence or history of ascites, clinical or ultrasound,
- Previous decompensation of liver cirrhosis, ascites or SBP, bleeding varices, large varices, hepatic encephalopathy, jaundice,
- Thrombosis splenoportal,
- Hepatocellular carcinoma;
- Child-Pugh >7 point
Show all 15Show fewer
- Any comorbidity that leads to a restriction therapy and / or a life expectancy <12 months
- Absolute contraindication to treatment with statins or allergy Simvastatin;
- Concomitant potent CYP3A4 inhibitors (eg., itraconazole, ketoconazole, protease inhibitors, HIV, erythromycin, clarithromycin, telithromycin and nefazodone),
- Pretreatment (<1 month) with simvastatin or other lipid-lowering,
- Previous episodes of rhabdomyolysis,
- Active alcoholic hepatitis,
- Refusal to participate in the study or the informed consent claim;
- Pre-treatment with beta blockers or nitrates, or endoscopic treatment for varicose veins or portosystemic derivations;
- Pregnancy and lactation.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Hospital de la Santa Creu i Sant Pau
Barcelona, Barcelona, 08025
Candido Villanueva, mPHD
Angela Puente, PHD
About this study
Official title: Prevention of Progression of Portal Hypertension in Compensated Cirrhosis Using Selective Hepatic Vasodilators. A Double-blind, Multicenter,Randomized Controlled Trial
The purpose of this study is to determine whether simvastatin is effective in the prevention of progression of porta hypertension in compensated cirrhosis patients.
Read the detailed description
Decompensation of cirrhosis is associated with a dramatic reduction of survival. Progression of portal hypertension (PHT) is the main determinant of decompensation that appears when portal pressure gradient (PPG) is ≥10mmHg (clinically significant HTP). 40% of compensated cirrhotic patients have mild PHT. However, with progression of disease 41% develop clinically significant PHT. In cirrhosis, PHT results from increased resistance to blood flow, with a dynamic component due to decreased nitric oxide (NO) bioavailability. In advanced disease increased portal venous inflow also contributes to PHT. Beta-blockers have not been useful in compensated cirrhosis with mild PHT. In early cirrhosis, vasodilators may be more adequate. Statins, drugs that inhibit the activity of HMG-CoA reductase, induce selective hepatic vasodilation due to an enhanced bioavailability of NO. Acutely, they decreases hepatic resistance, while with long-term use statins decreases PPG without deleterious effects on systemic circulation. This multicenter, randomized, double-blind placebo-controlled study is aimed at assessing whether treatment with simvastatin may prevent progression of mild PHT (with PPG between 6 and 10 mmHg) to clinically significant PHT. Patients with compensated cirrhosis, without previous decompensation, without esophageal varices at risk and with PPG between 6 and 10 mmHg will be included. The calculated sample size is 80 patients and the duration of the study 4 years (2 years including and a follow-up of at least 2 year).
- Conditions
- Portal Hypertension., Liver Cirrhosis
- Being tested
- Simvastatin, placebo
- Medical subject headings
- Hypertension, Portal, Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SimvastatinDrug
The experimental group will take 40 mg each 24 hours for at least two years.
placeboDrug
the control group wiil take placebo pills for at least two years.
| Study group | Role | What they receive |
|---|---|---|
| simvastatin | Experimental | The experimental group will take simvastatin 40mg for at least two years. Receives: Drug: Simvastatin |
| placebo | Placebo comparator | the control group wiil take placebo pills for at least two years. Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
the treatment of portal hypertension with simvastatin may prevent progression of portal hypertension
The main objective is to assess whether, in patients with compensated cirrhosis and mild portal hypertension (GPP between 6 and 10mmHg), the treatment of portal hypertension with simvastatin may prevent progression of portal hypertension and prevent the development of clinically significant HTP (defined GPP by a ≥ 10 mmHg)
Measured: 4 years
Secondary outcomes (2)
Portal hypertension complications
Development of complications related to portal hypertension (gastrointestinal bleeding related to portal hypertension, ascites, hepatic encephalopathy).
Measured: four years
Adverse effects
Measured: four years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2011 (estimated)
- Study startApr 2011
- Primary completionApr 2012 (estimated)
- Study completionApr 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Portal Hypertension.Studies of the same condition, open and under way.
- More trials run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto de Salud Carlos III
- Investigators
- Candido Villanueva, MD, Principal investigator, Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01282398
- Sponsor's protocol ID
- IIBSP-SIM-2010-06
- Acronym
- SIMPRO
- Status last verified
- Jan 2011
- First submitted
- 21 Jan 2011
- Last updated
- 25 Jan 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Abraldes JG, Albillos A, Banares R, Turnes J, Gonzalez R, Garcia-Pagan JC, Bosch J. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology. 2009 May;136(5):1651-8. doi: 10.1053/j.gastro.2009.01.043. Epub 2009 Jan 24.
PubMed 19208350Groszmann RJ, Garcia-Tsao G, Bosch J, Grace ND, Burroughs AK, Planas R, Escorsell A, Garcia-Pagan JC, Patch D, Matloff DS, Gao H, Makuch R; Portal Hypertension Collaborative Group. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med. 2005 Nov 24;353(21):2254-61. doi: 10.1056/NEJMoa044456.
PubMed 16306522Villanueva C, Aracil C, Colomo A, Hernandez-Gea V, Lopez-Balaguer JM, Alvarez-Urturi C, Torras X, Balanzo J, Guarner C. Acute hemodynamic response to beta-blockers and prediction of long-term outcome in primary prophylaxis of variceal bleeding. Gastroenterology. 2009 Jul;137(1):119-28. doi: 10.1053/j.gastro.2009.03.048. Epub 2009 Apr 1.
PubMed 19344721Zafra C, Abraldes JG, Turnes J, Berzigotti A, Fernandez M, Garca-Pagan JC, Rodes J, Bosch J. Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis. Gastroenterology. 2004 Mar;126(3):749-55. doi: 10.1053/j.gastro.2003.12.007.
PubMed 14988829Marrache MK, Rockey DC. Statins for treatment of chronic liver disease. Curr Opin Gastroenterol. 2021 May 1;37(3):200-207. doi: 10.1097/MOG.0000000000000716.
PubMed 33654016
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Progression of Portal Hypertension in Compensated Cirrhosis Using Selective Hepatic Vasodilators. A Double-blind, Multicenter,Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT01282398
- Acronym / sponsor ID
- SIMPRO / IIBSP-SIM-2010-06
- Conditions
- Portal Hypertension., Liver Cirrhosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant PauUniversity, hospital or other
- Collaborators
- Instituto de Salud Carlos III
- Study start
- Apr 2011
- Primary completion
- Apr 2012 (estimated)
- Study completion
- Apr 2015 (estimated)
- First posted
- 25 Jan 2011 (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.
The purpose of this study is to determine whether simvastatin is effective in the prevention of progression of porta hypertension in compensated cirrhosis patients.
Detailed description
Decompensation of cirrhosis is associated with a dramatic reduction of survival. Progression of portal hypertension (PHT) is the main determinant of decompensation that appears when portal pressure gradient (PPG) is ≥10mmHg (clinically significant HTP). 40% of compensated cirrhotic patients have mild PHT. However, with progression of disease 41% develop clinically significant PHT. In cirrhosis, PHT results from increased resistance to blood flow, with a dynamic component due to decreased nitric oxide (NO) bioavailability. In advanced disease increased portal venous inflow also contributes to PHT. Beta-blockers have not been useful in compensated cirrhosis with mild PHT. In early cirrhosis, vasodilators may be more adequate. Statins, drugs that inhibit the activity of HMG-CoA reductase, induce selective hepatic vasodilation due to an enhanced bioavailability of NO. Acutely, they decreases hepatic resistance, while with long-term use statins decreases PPG without deleterious effects on systemic circulation. This multicenter, randomized, double-blind placebo-controlled study is aimed at assessing whether treatment with simvastatin may prevent progression of mild PHT (with PPG between 6 and 10 mmHg) to clinically significant PHT. Patients with compensated cirrhosis, without previous decompensation, without esophageal varices at risk and with PPG between 6 and 10 mmHg will be included. The calculated sample size is 80 patients and the duration of the study 4 years (2 years including and a follow-up of at least 2 year).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| simvastatin | Experimental | Drug: SimvastatinThe experimental group will take simvastatin 40mg for at least two years. |
| placebo | Placebo comparator | Drug: placebothe control group wiil take placebo pills for at least two years. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Liver cirrhosis diagnosed by previous biopsy or by clinical, laboratory, ultrasound
- Portal hypertension gradient between6 mmHg and10 mmHg
- Absence of esophageal and gastric varices or small esophageal varices without red signs
- Absence previous episodes of gastrointestinal hemorrhage, ascites, encephalopathy or jaundice
- Written informed consent
Key exclusion criteria (15 listed)
- Age <18 and> 80 years,
- Presence or history of ascites, clinical or ultrasound,
- Previous decompensation of liver cirrhosis, ascites or SBP, bleeding varices, large varices, hepatic encephalopathy, jaundice,
- Thrombosis splenoportal,
- Hepatocellular carcinoma;
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 |
|---|---|---|
| SimvastatinThe experimental group will take 40 mg each 24 hours for at least two years. | Drug | simvastatin |
| placebothe control group wiil take placebo pills for at least two years. | Drug | placebo |
Primary outcome
the treatment of portal hypertension with simvastatin may prevent progression of portal hypertension
Time frame: 4 years
The main objective is to assess whether, in patients with compensated cirrhosis and mild portal hypertension (GPP between 6 and 10mmHg), the treatment of portal hypertension with simvastatin may prevent progression of portal hypertension and prevent the development of clinically significant HTP (defined GPP by a ≥ 10 mmHg)
2 secondary outcomes
Portal hypertension complications
Time frame: four years
Adverse effects
Time frame: four years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2011.
- Results publication: PubMed 19208350Abraldes JG, Albillos A, Banares R, Turnes J, Gonzalez R, Garcia-Pagan JC, Bosch J. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology. 2009 May;136(5):1651-8. doi: 10.1053/j.gastro.2009.01.043. Epub 2009 Jan 24.
- Results publication: PubMed 16306522Groszmann RJ, Garcia-Tsao G, Bosch J, Grace ND, Burroughs AK, Planas R, Escorsell A, Garcia-Pagan JC, Patch D, Matloff DS, Gao H, Makuch R; Portal Hypertension Collaborative Group. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med. 2005 Nov 24;353(21):2254-61. doi: 10.1056/NEJMoa044456.
- Results publication: PubMed 19344721Villanueva C, Aracil C, Colomo A, Hernandez-Gea V, Lopez-Balaguer JM, Alvarez-Urturi C, Torras X, Balanzo J, Guarner C. Acute hemodynamic response to beta-blockers and prediction of long-term outcome in primary prophylaxis of variceal bleeding. Gastroenterology. 2009 Jul;137(1):119-28. doi: 10.1053/j.gastro.2009.03.048. Epub 2009 Apr 1.
- Results publication: PubMed 14988829Zafra C, Abraldes JG, Turnes J, Berzigotti A, Fernandez M, Garca-Pagan JC, Rodes J, Bosch J. Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis. Gastroenterology. 2004 Mar;126(3):749-55. doi: 10.1053/j.gastro.2003.12.007.
- Derived from this study: PubMed 33654016Marrache MK, Rockey DC. Statins for treatment of chronic liver disease. Curr Opin Gastroenterol. 2021 May 1;37(3):200-207. doi: 10.1097/MOG.0000000000000716.
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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.
Candido Villanueva, MD principal investigator
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Simvastatin in people with Portal Hypertension. and Liver Cirrhosis, run by Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau at 1 site 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 5 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 25 Jan 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Candido Villanueva, PHD (935565917, cvillanueva@santpau.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the treatment of portal hypertension with simvastatin may prevent progression of portal hypertension (time frame: 4 years). 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 NCT01282398, which also lists 5 linked publications.
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 25 Jan 2011.