Multi-Center Study of the Effects of Simvastatin on Hepatic Decompensation and Death in Subjects Presenting With High-Risk Compensated Cirrhosis

• Status: Recruiting
• Trial end date: 2024-09-30
• Target enrollment: 0
• Participant gender: All

Summary

This phase III, randomized, double-blind, placebo-controlled, multi-center study seeks to test whether simvastatin, a statin usually used to lower cholesterol to prevent heart problems and strokes, can lower the risk of hepatic decompensation (developing symptoms of cirrhosis) in U.S. Veterans who have compensated cirrhosis (the liver is scarred and damaged but there are no symptoms). The study will also explore how changes or differences in genes effect the safety and effectiveness of using statins and how the use of statins affects quality of life.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Tamar Taddei; VA Office of Research and Development
• Treatments: Simvastatin

Criteria

Inclusion Criteria:

• U.S. Veteran

• Cirrhosis due to chronic viral hepatitis, or alcohol or non-alcoholic fatty liver

• Compensated cirrhosis (history of endoscopically-confirmed variceal hemorrhage, absence of overt ascites, history of overt non-precipitated encephalopathy)

• Age > 18 and <= 80

• High risk of cirrhosis decompensation as defined by any of the following:

• Presence of esophageal varices on endoscopy

• Presence of portosystemic collaterals on imaging as determined by a body radiologist

• Fibroscan VCTE >= 25kPa

• Platelet count <= 110 K/mm

• 44 total points (~50% of clinically significant portal hypertension using the ANTICIPATE Nomogram)

• Competent to provide informed consent

Exclusion Criteria:

• Prior exposure to any statin within 2 years

• Prior allergy or sensitivity to simvastatin

• History of variceal hemorrhage confirmed endoscopically within the previous 2 years

• Presence of overt ascites or treatment with diuretics for ascites

• History of chronic, recurrent or episodic overt hepatic encephalopathy with asterixis

• History of hepatocellular carcinoma

• Child-Turcotte-Pugh C Stage (CTP Score > 9)

• Prior receipt of organ transplant

• Participation in another pharmacological clinical trial within 3 months of the current study

• Pregnancy or anticipated pregnancy within 2 years

• Breast Feeding

• Patients with life expectancy < 3 years due to comorbid conditions

• Independent indication for initiation of statin therapy

• Patients with any form of clinical atherosclerotic cardiovascular disease (ASCVD)

• Patients with primary LDL-C < 190 mg/dl

• Patients with diabetes mellitus, age 40-75 years, with LDL-C levels of 70-189 mg/dl

• Patients without diabetes, age 40-75 years, with an estimated 10-year ASCVD risk < 16%

• Need for concomitant administration of potent inhibitors of CYP34A4 enzymes (medications or other supplements that should not be taken with simvastatin, including cyclosporine, danazol, gemfibrozil, fenofibrate, extended release niacin, itraconazole, ketoconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, macrolide antibiotics - erythromycin, clarithromycin, telithromycin, nefazadone, verapamil, diltiazem, dronedarone, amiodarone, renolazine, lomitapide, and cobicistat)

• Prior TIPSS shunt