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

50 Participants Needed

Trial Summary

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.

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

Research suggests that atorvastatin may help reduce portal pressure in patients with liver cirrhosis, which can lower the risk of complications and mortality. This is based on its anti-inflammatory and antifibrotic effects, as well as its ability to modulate blood flow in the liver. ^{1 2 3 4 5}

Is the combination of Atorvastatin and Beta Blockers safe for people with liver cirrhosis?

Research shows that statins like Atorvastatin are being studied for their safety in people with cirrhosis, and they may help reduce liver problems. Non-selective beta blockers have mixed safety results; they don't seem to increase death rates in some cirrhosis patients, but they might increase risks in others, especially with severe liver issues. ^{1 4 6 7 8}

How is the drug Atorvastatin + Beta Blockers unique for treating liver cirrhosis?

This treatment combines atorvastatin, which can improve blood flow in the liver, with beta blockers, which are traditionally used to prevent bleeding in cirrhosis. The combination aims to reduce portal pressure more effectively than beta blockers alone, potentially offering a new approach for managing cirrhosis with portal hypertension. ^{1 2 4 8 9}

What is the purpose of this trial?

Decompensated cirrhosis (liver disease) occurs when liver function decreases to the extent that serious complications develop and can include internal bleeding, fluid buildup in the abdomen, or mental confusion. This reduced decreased liver function subsequently decreases life expectancy. There is a critical need for strategies to delay progression to decompensation and reduce the occurrence of serious complications. Currently, limited therapeutic options are available for managing decompensated liver disease, with beta-blockers (BB) being the only proven medication with significant benefits in preventing disease progression. Statins have been historically under- prescribed in cirrhosis due to concerns of liver damage. However, there is emerging evidence that statin use may be beneficial and able to lessen liver disease worsening, with studies demonstrating its safety. Thus, we aim to conduct a pilot randomized controlled trial (RCT) study of 50 subjects comparing the outcomes of decompensated cirrhotic patients receiving the statin, atorvastatin, and a non-selective beta-blocker (NSBB) versus those receiving NSBB plus placebo. Both groups will be followed for 12 months to investigate the feasibility, safety, and efficacy of combination therapy.

Research Team

Nadeem Anwar, MD

Principal Investigator

CAMC Health System

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Non-selective beta-blockers increase overall and liver mortality in alcoholic cirrhosis with MELD ≥ 12 over 5 years of follow-up. [2021]

2. England 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. [2018]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Systemic arterial blood pressure determines the therapeutic window of non-selective beta blockers in decompensated cirrhosis. [2020]

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

Atorvastatin for patients with cirrhosis. A randomized, placebo-controlled trial. [2023]

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

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

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

Nonselective β-blockers do not affect mortality in cirrhosis patients with ascites: Post Hoc analysis of three randomized controlled trials with 1198 patients. [2022]

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

Nonselective beta blockers, hepatic decompensation, and mortality in cirrhosis: A national cohort study. [2023]

9. Romania pubmed.ncbi.nlm.nih.gov

NONSELECTIVE BETA-BLOCKERS IN PATIENTS WITH CIRRHOSIS: "THE THERAPEUTIC WINDOW". [2016]