Atorvastatin + Beta Blockers for Liver Cirrhosis

Overseen By Nadeem Anwar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: CAMC Health System

Must be taking: Non-selective beta-blockers

Must not be taking: Statins, interacting medications

Disqualifiers: Hepatocellular carcinoma, alcohol use, others

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

Compensation: Varies

Number of Visits: 4

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for individuals with decompensated liver disease, a serious condition marked by significant liver function decline. The trial tests whether combining atorvastatin, a cholesterol-lowering drug, with beta-blockers can manage the disease more effectively than beta-blockers alone. Participants will receive either atorvastatin with their regular beta-blocker or a placebo for 12 months to assess the combination's safety and effectiveness. Suitable candidates have decompensated liver disease and are already taking beta-blockers for their condition. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in managing their condition.

Will I have to stop taking my current medications?

The trial requires participants to already be on a non-selective beta-blocker, but you cannot be on statin therapy or medications that interact with statins. If you're taking such medications, you may need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that atorvastatin, a cholesterol-lowering medication, is generally safe for people with liver cirrhosis. In one study, patients with cirrhosis who took atorvastatin did not experience more liver-related problems. Another study found that regular statin use was linked to a lower risk of developing new liver diseases and fewer liver-related deaths. These findings suggest that atorvastatin is well-tolerated and may even help protect the liver.

This trial also includes non-selective beta-blockers (NSBB), which are known to help manage liver disease by slowing its progression. The current trial tests whether combining these beta-blockers with atorvastatin is safe and effective for people with advanced liver cirrhosis. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using atorvastatin for liver cirrhosis because it offers a new approach to managing the condition. While current treatments often focus on managing symptoms and complications, atorvastatin works by reducing inflammation and fibrosis in the liver. This is different from the standard care options, like beta blockers, which primarily aim to reduce portal hypertension. By potentially addressing the underlying liver damage, atorvastatin could offer significant improvements in liver function and overall health for patients with cirrhosis.

What evidence suggests that this trial's treatments could be effective for liver cirrhosis?

Research has shown that atorvastatin might aid in treating liver disease. Some studies indicate that statins, such as atorvastatin, can lower the risk of liver-related deaths by 28% and reduce the chance of developing new liver problems by 15%. Atorvastatin is considered safe for individuals with cirrhosis, although it did not lower death rates for all patients. Additionally, statins can improve liver health by reducing inflammation and stress on the liver. In this trial, participants will receive either atorvastatin or a placebo, both in combination with previously prescribed non-selective beta blockers (NSBB). While researchers continue to study atorvastatin's effects on liver disease, these findings suggest it could be beneficial. ^{1 2 3 4 6}

Who Is on the Research Team?

Nadeem Anwar, MD

Principal Investigator

CAMC Health System

Are You a Good Fit for This Trial?

This trial is for patients with advanced liver disease (decompensated cirrhosis) who often face complications like fluid in the abdomen or mental confusion. Participants should not have other conditions that could interfere with the study or be taking medications that might conflict with the trial drugs.

Inclusion Criteria

I am 18 or older with advanced liver disease, seen at CAMC.

I am taking beta-blockers and agree to liver disease management by CAMC-Gastroenterology for 12 months.

Exclusion Criteria

Patients on the waitlist for liver transplantation

I have been diagnosed with liver cancer.

Patients with ongoing alcohol use (self-reported consumption of more than one alcoholic drink per week)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either atorvastatin and NSBB or NSBB plus placebo

12 months

4 follow-up visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atorvastatin
• Placebo

Trial Overview The study tests if adding atorvastatin, a statin drug, to a non-selective beta-blocker (a common treatment for liver disease), can help manage decompensated cirrhosis better than a beta-blocker alone. It's a pilot randomized controlled trial where half of the participants will receive atorvastatin and half will get a placebo.

How Is the Trial Designed?

Group I: NSBB plus statin Active Control 1 Intervention

Atorvastatin 20 mg once daily along with previously prescribed NSBB

Group II: NSBB plus placebo Placebo Group 1 Intervention

Placebo once daily along with previously prescribed NSBB

Who Is Running the Clinical Trial?

CAMC Health System

Lead Sponsor

Trials

47

Recruited

8,000+

Published Research Related to This Trial

In a study of 23 patients with cirrhosis, the combination of atorvastatin and propranolol significantly reduced portal pressure more than propranolol alone, with a decrease in hepatic venous pressure gradient (HVPG) of 4.81 mmHg compared to 2.58 mmHg for propranolol alone.

The combination treatment resulted in a higher proportion of HVPG responders (90.91% in the atorvastatin group versus 50.00% in the propranolol group), suggesting that atorvastatin may enhance the effectiveness of propranolol in managing portal hypertension in cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of atorvastatin on portal hemodynamics and clinical outcomes in patients with cirrhosis with portal hypertension: a proof-of-concept study. Bishnu, S., Ahammed, SM., Sarkar, A., et al.[2018]

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, known for lowering cholesterol, also have beneficial effects in cirrhosis patients, including anti-inflammatory properties and potential to reduce the risk of liver complications and mortality, based on retrospective studies.

Ongoing clinical trials are expected to provide more insights into the safety and effectiveness of statins in treating cirrhosis, which could influence future treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging role of statin therapy in the prevention and management of cirrhosis, portal hypertension, and HCC. Sharpton, SR., Loomba, R.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10697620/

Atorvastatin for patients with cirrhosis. A randomized ... In patients with cirrhosis, atorvastatin was safe to use, but did not reduce mortality, the risk of liver-related complications, or the HVPG.

2. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00363-3/fulltext

Age-specific protective effects of statins against cirrhosis in ... A minimum treatment duration of eight months per year was effective in preventing cirrhosis in individuals aged ≥54 years, but not in those <54 ...

3. ahajournals.org ahajournals.org/doi/10.1161/JAHA.122.028310

High‐Intensity Statin Reduces the Risk of Mortality Among ... Among patients with CLD with atherosclerotic cardiovascular disease, high‐intensity statin was significantly associated with a lower risk of mortality.

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2806370

Statin Use and Risk of Liver Disease, Hepatocellular ... Regular use of statins was associated with a 15% lower hazard ratio of new-onset liver disease and a 28% lower hazard ratio for liver-related deaths compared ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0753332224016925

Statins and non-alcoholic fatty liver disease: A concise review Statins show beneficial effects beyond lipid lowering by improving fibrosis, inflammation, oxidative stress and microcirculation in NAFLD/NASH.

6. bmcgastroenterol.biomedcentral.com bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-021-01704-w

A systematic review on pharmacokinetics, cardiovascular ... Atorvastatin showed pronounced PK changes in cirrhosis. No PK data was found for simvastatin, the most commonly used statin in cirrhosis trials.