Summary

Eligibility
for people ages 18-80 (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion

Description

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.

Official Title

Effect of Simvastatin on Hepatic Decompensation and Death in Subjects With High-risk Compensated Cirrhosis

Details

HMG-coA reductase inhibitors (statins), independent of cholesterol-lowering effects, are beneficial in liver diseases by reducing endothelial dysfunction, intrahepatic vasoconstriction, inflammation and fibrosis, and can reduce portal vein blood pressure. Clinically significant portal hypertension (hepatic vein wedge pressure greater than or equal to 10mmHg) is the most important predictor of decompensation and death in patients with cirrhosis.

This randomized, double-blind, placebo-controlled, multi-center Phase III interventional study seeks to demonstrate that statin therapy in patients with cirrhosis at high-risk for hepatic decompensation will reduce the incidence of hepatic decompensation, hepatocellular carcinoma or all-cause mortality.

Patients with compensated cirrhosis at high-risk for hepatic decompensation will be stratified based on the presence or absence of varices and randomized to simvastatin 40mg/day for up to 24 months. Patients will be observed for the development of hepatic decompensation (variceal hemorrhage, ascites, encephalopathy), hepatocellular carcinoma, liver-related death, death from any cause, and/or complications of statin therapy. Additionally, the interaction of SLCO1B1 and KIF6 polymorphisms on safety and clinical efficacy of statin therapy and the impact of statin exposure on health-related quality of life in patients with compensated cirrhosis will be examined.

Keywords

Cirrhosis hepatic decompensation HMG-coA reductase hepatocellular carcinoma clinical trial Human Liver Cirrhosis Fibrosis Simvastatin Simvastatin 40mg

Eligibility

You can join if…

Open to people ages 18-80

  • 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 70 K/mm
  • 60 total points (~67% of clinically significant portal hypertension using the ANTICIPATE Nomogram)
  • Competent to provide informed consent

You CAN'T join if...

  • 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 7.5%
  • 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)

Locations

  • San Francisco VA Medical Center, San Francisco, CA accepting new patients
    San Francisco California 94121 United States
  • VA Puget Sound Health Care System Seattle Division, Seattle, WA accepting new patients
    Seattle Washington 98108 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
VA Office of Research and Development
ID
NCT03654053
Phase
Phase 3
Study Type
Interventional
Last Updated