Simvastatin for Liver Cirrhosis

(SACRED Trial)

Recruiting at 10 trial locations

Overseen By David E Kaplan, MD MSc

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: VA Office of Research and Development

Must not be taking: CYP34A4 inhibitors

Disqualifiers: Statin use, Hepatocellular carcinoma, ASCVD, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

142 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you need to take certain medications that interact with simvastatin. These include some antibiotics, antifungals, and heart medications, among others.

Is simvastatin safe for people with liver cirrhosis?

Simvastatin can be safe for people with liver cirrhosis, but it should be used carefully, especially in those with severe liver problems. The most serious side effect is muscle injury, which can be life-threatening, so lower doses are recommended for those with severe liver issues. ^{1 2 3 4 5}

How does the drug simvastatin differ from other treatments for liver cirrhosis?

Simvastatin is unique in treating liver cirrhosis because it not only lowers cholesterol but also reduces inflammation and portal pressure, which can improve liver function and reduce the risk of complications like variceal bleeding. Unlike some other treatments, it has been shown to improve outcomes in patients with decompensated cirrhosis and has a safety profile that supports its use in these patients. ^{2 3 5 6 7}

What data supports the effectiveness of the drug Simvastatin for liver cirrhosis?

Research shows that Simvastatin can help people with liver cirrhosis by reducing inflammation and lowering blood pressure in the liver, which can improve survival rates and reduce the risk of liver-related complications. ^{1 2 3 5 8}

Who Is on the Research Team?

David E Kaplan, MD MSc

Principal Investigator

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

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

My liver disease is stable with specific health criteria met.

Exclusion Criteria

I have had liver cancer in the past.

Patients with life expectancy < 3 years due to comorbid conditions

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in

Participants trial 20mg simvastatin once at bedtime for two weeks to determine tolerability prior to randomization

2 weeks

Treatment

Participants receive simvastatin 40mg/day or placebo for up to 24 months

24 months

Regular visits for monitoring liver enzyme levels and other health parameters

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Simvastatin

Trial Overview 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.

How Is the Trial Designed?

Group I: Simvastatin Experimental Treatment 1 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: Placebo Placebo Group 1 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.

Simvastatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Zocor for:

• Hypercholesterolemia
• Cardiovascular disease

Approved in United States as Zocor for:

• Hypercholesterolemia
• Cardiovascular disease

Approved in Canada as Zocor for:

• Hypercholesterolemia
• Cardiovascular disease

Approved in Japan as Zocor for:

• Hypercholesterolemia
• Cardiovascular disease

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

In a study of 30 patients with decompensated cirrhosis, simvastatin treatment for one year significantly reduced cirrhosis severity, particularly in patients who improved from Child-Pugh class B to A, indicating its potential efficacy in managing cirrhosis.

Patients who responded positively to simvastatin also experienced improved health-related quality of life and fewer hospitalizations for cirrhosis complications, suggesting that simvastatin may have beneficial anti-inflammatory effects in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline Severity and Inflammation Would Influence the Effect of Simvastatin on Clinical Outcomes in Cirrhosis Patients. Muñoz, AE., Pollarsky, F., Marino, M., et al.[2023]

Statins, commonly used for lowering cholesterol, are safe for patients with chronic liver disease and cirrhosis, and they may even reduce mortality and the risk of liver complications.

The review highlights that statins can help decrease complications in liver cirrhosis by addressing issues like portal hypertension, sepsis, and the risk of liver cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety and Benefit of Statins in Liver Cirrhosis: a Review. Souk, K., Al-Badri, M., Azar, ST.[2015]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Simvastatin is Efficacious in Treating Cirrhosis: A Meta-analysis. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Baseline Severity and Inflammation Would Influence the Effect of Simvastatin on Clinical Outcomes in Cirrhosis Patients. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

SACRED: Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis: Statins and Cirrhosis: Reducing Events of Decompensation. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Addition of statins to the standard treatment in patients with cirrhosis: Safety and efficacy. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

The Safety and Benefit of Statins in Liver Cirrhosis: a Review. [2015]

6. United States pubmed.ncbi.nlm.nih.gov

The Use of Statins in Patients With Chronic Liver Disease and Cirrhosis. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Simvastatin Attenuates Liver Injury in Rodents with Biliary Cirrhosis Submitted to Hemorrhage/Resuscitation. [2018]

8. England pubmed.ncbi.nlm.nih.gov

A Nitric Oxide-Donating Statin Decreases Portal Pressure with a Better Toxicity Profile than Conventional Statins in Cirrhotic Rats. [2018]