What side effects are associated with this type of intervention?

Common treatments for liver cirrhosis, particularly those involving statins like simvastatin, are generally well-tolerated but can have side effects. These may include muscle pain or weakness (myopathy), liver enzyme abnormalities (transaminitis), and, in rare cases, more severe liver damage. Other potential side effects include gastrointestinal issues such as nausea and constipation, as well as an increased risk of diabetes. It is important for patients to be monitored regularly by their healthcare provider to manage and mitigate these risks.

What prior FDA approvals exist?

The FDA has not specifically approved statins like simvastatin for the treatment of liver cirrhosis. However, statins have been studied for their potential benefits in patients with liver conditions, including cirrhosis. Simvastatin, an HMG-CoA reductase inhibitor, is being investigated in clinical trials for its ability to lower the risk of hepatic decompensation in patients with compensated cirrhosis. Other statins, such as atorvastatin, have also been explored for their effects on liver disease, but their primary FDA approval remains for managing dyslipidemia and cardiovascular risk.

What other types of research exist?

Promising alternatives to Simvastatin for liver cirrhosis patients include PCSK9 inhibitors such as alirocumab and evolocumab, as well as inclisiran. These drugs effectively lower LDL-C and have been shown to be safe in patients with mild to moderate hepatic impairment.

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Statin

Simvastatin for Liver Cirrhosis (SACRED Trial)

Phase 3

Waitlist Available

Led By David E. Kaplan, MD MSc

Research Sponsored by VA Office of Research and Development

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

High risk of cirrhosis decompensation as defined by specific criteria

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

Must not have

History of hepatocellular carcinoma

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 24 months

Awards & highlights

Pivotal Trial

Summary

This trial tests if simvastatin can prevent serious liver problems in U.S. Veterans with early-stage liver damage. Simvastatin not only lowers cholesterol but also helps protect the liver from further damage and reduces the risk of severe liver issues. Statins, including simvastatin, have been increasingly recognized for their potential benefits in treating chronic liver diseases, including cirrhosis, by reducing portal pressure and protecting against liver damage.

Who is the study for?

This trial is for U.S. Veterans aged 18-80 with compensated cirrhosis, indicated by specific liver conditions and test results. Participants must not have had certain complications like overt ascites or hepatic encephalopathy recently, no history of hepatocellular carcinoma, and should not be on conflicting medications or have other severe health issues.

What is being tested?

The study tests if Simvastatin (40mg), a drug normally used to lower cholesterol, can prevent worsening symptoms in patients with high-risk compensated cirrhosis compared to a placebo. It's randomized and double-blind, meaning neither the researchers nor participants know who gets the real medicine.

What are the potential side effects?

Simvastatin may cause muscle pain or weakness, liver enzyme changes leading to potential liver damage, digestive problems like constipation or nausea, increased blood sugar levels which could lead to diabetes risk increase.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am at high risk for my liver condition getting worse.

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I have cirrhosis caused by hepatitis, alcohol, or fatty liver disease.

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My liver disease is stable with specific health criteria met.

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I understand and can agree to the study's procedures and risks.

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I am between 18 and 80 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had liver cancer in the past.

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My liver disease is severe (CTP Score > 9).

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I have had episodes of severe liver-related brain dysfunction in the last 6 months.

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I need to start taking statins for my health.

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I have a condition related to the hardening of my arteries.

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I need to take strong medication that affects liver enzymes.

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I am on hemodialysis.

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I am between 40-75 years old, have diabetes, and my LDL cholesterol is 130 mg/dl or higher.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Survival free from hepatic decompensation

Secondary study objectives

Change in patient health-related quality of life

Hepatotoxicity

Liver-related death

+4 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: SimvastatinExperimental Treatment1 Intervention

Simvastatin 40mg PO once at bedtime for up to 24 months. Note: all enrolled subjects will trial 20mg once at bedtime for two weeks as lead-in to determine tolerability prior to randomization.

Group II: PlaceboPlacebo Group1 Intervention

Placebo 40mg PO once at bedtime for up to 24 months. Note: all enrolled subjects will trial 20mg once at bedtime for two weeks as lead-in to determine tolerability prior to randomization.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Simvastatin 40mg

2018

Completed Phase 2

~160

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Statins, such as simvastatin, are commonly used in the treatment of liver cirrhosis due to their ability to inhibit HMG-CoA reductase, an enzyme crucial for cholesterol synthesis. By lowering cholesterol levels, statins help reduce liver inflammation and fibrosis, which are key factors in the progression of cirrhosis. Moreover, statins have been associated with a decreased risk of hepatic decompensation and hepatocellular carcinoma, making them valuable in improving liver function and reducing complications in cirrhosis patients.

SACRED: Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis: Statins and Cirrhosis: Reducing Events of Decompensation.An Evidence-Based Review of Statin Use in Patients With Nonalcoholic Fatty Liver Disease.