Hemodynamic Effect of Simvastatin With Beta Blockers in Clinical Portal Hypertension

NCT01282385 | Unknown Phase 4 DMC

• 1 other identifier: IIBSP-SIM-2010-04
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

In the genesis and maintenance of PH associated with liver cirrhosis are two mechanisms that act synergistically. The first is an increase in hepatic vascular resistance, due in part to the disruption of liver structure inherent cirrhosis, and increased hepatic vascular tone is caused by the contraction of perivascular smooth muscle cells, myofibroblasts and hepatic stellate cells, which represents about 30% of global intrahepatic resistance and is believed to be due to the production Defective nitric oxide (NO). The second mechanism, which maintains and exacerbates HTP, is an increase of splanchnic blood flow caused by increased NO and other vasodilators at this level In this regard, we believe that in patients with compensated liver cirrhosis, with portal pressure gradient\> 10 mmHg, both acute responders betablockers test as non-responders, the association of antifibrotic drugs and / or vasodilators, chronic liver selective May be beneficial in the control of portal hypertension

Conditions

Liver Cirrhosis; Portal Hypertension.

Outcome Measures

Primary Outcomes (1)

• improvement of the hemodynamic response rate

  The main objective is to assess whether, in patients with compensated cirrhosis, portal pressure greater than 10mmHg and esophageal varices at risk, the association of a liver selective vasodilator and simvastatin together with non-cardioselective beta blockers can improve the hemodynamic response rate.

  1 month.

Secondary Outcomes (2)

• Portal hypertension complications.

  1 month

• Adverse effects

  1 month

Study Arms (2)

simvasatin

EXPERIMENTAL

a) patients responding to treatment with beta-blockers, in which she was treated with nadolol Subsequently randomized into two treatment arms, double-blind: a.1: simvastatin 20 mg capsules, starting at doses of 20 mg / 24 hours, may increase to 40 mg according to clinical and laboratory tolerance. a.2: placebo capsules with external characteristics similar to simvastatin. b) non-responders to treatment with beta blockers, receive treatment with carvedilol.Subsequently randomized into two treatment arms, double-blind b.1: simvastatin 20 mg capsules, starting at doses of 20 mg / 24 hours, may increase to 40 mg according to clinical and laboratory tolerance. b.2: placebo capsules with external characteristics similar to simvastatin.

Drug: Simvastatin

placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

Simvastatin DRUG

simvastatin 20 mg capsules, starting at doses of 20 mg / 24 hours, may increase to 40 mg according to clinical and laboratory tolerance

simvasatin

placebo DRUG

placebo capsules with external characteristics similar to simvastatin administrated each 24 hours.

placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Liver cirrhosis diagnosed by previous biopsy or by clinical, laboratory, ultrasound,
• PPG\> 10 mmHg,
• Presence of large esophageal varices or small varices with red spots, varices of any size and Pugh C, and / or gastric fundic varices of any size, in a recent gastroscopy (\<1 month)
• Absence of previous episodes of gastrointestinal bleeding
• Written informed consent.

You may not qualify if:

• Age \<18 and\> 80 years;
• Episode of variceal bleeding,
• Thrombosis splenoportal axis,
• Hepatocarcinoma,
• Terminal liver failure (Child-Pugh scale\> 13 points);
• Any comorbidity involving a medical drugs and / or a life expectancy \<12 months,
• Severe chronic renal insufficiency (creatinine\> 150 g / L),
• Absolute contraindication or allergy treatment with statins to simvastatin;
• Concomitant potent inhibitors of CYP3A4 (eg., itraconazole, ketoconazole, inhibitors of HIV protease, erythromycin, clarithromycin, telithromycin and nefazodone),
• Pretreatment (\<1 month) or other lipid-lowering with simvastatin,
• Previous episodes rhabdomyolysis;
• Contraindication to beta-blockers (COPD with bronchial hyperresponsiveness, aortic stenosis, AV block, intermittent claudication, severe psychosis, bronchial asthma),
• Hypersensitivity to beta blockers,
• Concomitant administration of potent inhibitors of cytochrome P-450 (quinidine, fluoxetine, paroxetine, and propafenone)
• Active alcoholic hepatitis,

Sponsors & Collaborators

• Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau: lead

Study Sites (1)

Hospital de la Santa Creu i Sant Pau

Barcelona, Barcelona, 08025, Spain

Location

Related Publications (4)

• Bosch J. Carvedilol for portal hypertension in patients with cirrhosis. Hepatology. 2010 Jun;51(6):2214-8. doi: 10.1002/hep.23689. No abstract available.

  PMID: 20513005 BACKGROUND

• Trebicka J, Hennenberg M, Laleman W, Shelest N, Biecker E, Schepke M, Nevens F, Sauerbruch T, Heller J. Atorvastatin lowers portal pressure in cirrhotic rats by inhibition of RhoA/Rho-kinase and activation of endothelial nitric oxide synthase. Hepatology. 2007 Jul;46(1):242-53. doi: 10.1002/hep.21673.

  PMID: 17596891 BACKGROUND

• 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.

  PMID: 19208350 RESULT

• Tripathi D, Therapondos G, Lui HF, Stanley AJ, Hayes PC. Haemodynamic effects of acute and chronic administration of low-dose carvedilol, a vasodilating beta-blocker, in patients with cirrhosis and portal hypertension. Aliment Pharmacol Ther. 2002 Mar;16(3):373-80. doi: 10.1046/j.1365-2036.2002.01190.x.

  PMID: 11876689 RESULT

MeSH Terms

Conditions

Liver Cirrhosis; Hypertension, Portal

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Candido Villanueva, MD

  Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Candido Villanueva, PHD

CONTACT

0034 5565917; cvillanueva@santpau.cat

Angela Puente, MD

CONTACT

00345565917; apuentesa@santpau.cat

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 21, 2011
• First Posted: January 25, 2011
• Study Start: April 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: January 25, 2011

Record last verified: 2011-01

Locations

ES (1)