Study About Simvastatin in Portal Hypertension in Compensated Cirrhosis (SIMPRO)

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

Status and phase: Unknown; Phase 4

Conditions: Liver Cirrhosis; Portal Hypertension.

Treatments: Drug: Simvastatin; Drug: placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT01282398

IIBSP-SIM-2010-06

Details and patient eligibility

About

The purpose of this study is to determine whether simvastatin is effective in the prevention of progression of porta hypertension in compensated cirrhosis patients.

Full 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).

Enrollment: 80 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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
• 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 design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

80 participants in 2 patient groups, including a placebo group

simvastatin

Experimental group

Description:

The experimental group will take simvastatin 40mg for at least two years.

Treatment:

Drug: Simvastatin

placebo

Placebo Comparator group

Description:

the control group wiil take placebo pills for at least two years.

Treatment:

Drug: placebo