Hemodynamic Effect of Simvastatin With Beta Blockers in Clinical Portal Hypertension

• Status: Unknown status
• Trial end date: 2014-04-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Treatments: Adrenergic beta-Antagonists; Simvastatin

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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,

• 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 shunts;

• Pregnancy and lactation.