Rosuvastatin for Liver Cirrhosis

(LCN RESCU Trial)

Recruiting at 12 trial locations

Overseen By Crystal Santillanes

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Must not be taking: Statins, Amiodarone, Methotrexate, others

Disqualifiers: Hepatocellular carcinoma, Portal thrombosis, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 96 weeks

256 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a double-blind, phase 2 study to evaluate safety and efficacy of rosuvastatin in comparison to placebo after 2 years in patients with compensated cirrhosis.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as statins, and some others that could interfere with the study. If you're on any of these, you may need to stop them before joining the trial.

Is rosuvastatin safe for use in humans, including those with liver cirrhosis?

Rosuvastatin has been studied in over 12,000 patients and generally shows a similar safety profile to other statins, with uncommon serious side effects. For people with liver cirrhosis, several studies suggest that statins, including rosuvastatin, are safe and may even reduce complications and mortality. ^{1 2 3 4 5}

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

Rosuvastatin is unique because it is a statin that selectively targets liver cells, reducing cholesterol with minimal interaction with other drugs, which may be beneficial in managing liver cirrhosis. Its high potency and low risk of drug interactions make it a novel option compared to other treatments that may not specifically target liver cells. ^{2 6 7 8 9}

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

Rosuvastatin is known for its ability to lower cholesterol and reduce inflammation, which may be beneficial for liver health. It has been shown to be effective in reducing cholesterol levels and preventing cardiovascular events in other conditions, suggesting potential benefits for liver cirrhosis. ^{2 6 7 8 10}

Who Is on the Research Team?

Jody Ciolino

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

Adults aged 18-75 with compensated cirrhosis due to nonalcoholic steatohepatitis, alcohol-associated liver disease, chronic viral hepatitis, or cryptogenic causes. Participants must have a clinical diagnosis of cirrhosis confirmed by biopsy or other criteria and cannot be on statins or have conditions like uncontrolled diabetes, recent serious cardiovascular events, active substance abuse, certain infections or cancers.

Inclusion Criteria

I have been diagnosed with cirrhosis caused by fatty liver, alcohol, viral hepatitis, or unknown reasons.

My liver disease is stable without severe symptoms.

My cirrhosis has been confirmed by a doctor using tests or imaging.

Exclusion Criteria

I have chronic hepatitis B or C that has not been treated.

I experience significant muscle pain or tenderness.

Documented history of statin intolerance

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in

Open-label active run-in phase to evaluate initial safety and adherence to rosuvastatin

4 weeks

1 visit (in-person)

Treatment

Participants receive either rosuvastatin or placebo for 96 weeks

96 weeks

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Rosuvastatin

Trial Overview The trial is testing the safety and effectiveness of rosuvastatin versus a placebo in patients with compensated cirrhosis over two years. It's a phase 2 study where neither the participants nor the researchers know who receives the actual medication (double-blind).

How Is the Trial Designed?

Group I: Active Experimental Treatment 1 Intervention

Open-label lead-in period of 4 weeks on 20 mg (10 mg for participants of East ancestry) rosuvastatin by mouth once daily, followed by a period of 96 weeks rosuvastatin 20 mg daily (10 mg daily for participants of East-Asian ancestry).

Group II: Placebo Placebo Group 1 Intervention

Open-label lead-in period of 4 weeks on 20 mg (10 mg for participants of East ancestry) rosuvastatin by mouth once daily, followed by a period of 96 weeks placebo.

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

Approved in United States as Crestor for:

• High cholesterol
• Hyperlipoproteinemia
• Prevention of cardiovascular disease

Approved in European Union as Crestor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in Canada as Crestor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

Approved in Japan as Crestor for:

• Hypercholesterolemia
• Familial hypercholesterolemia

Who Is Running the Clinical Trial?

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lead Sponsor

Trials

2,513

Recruited

4,366,000+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Columbia University

Collaborator

Trials

1,529

Recruited

2,832,000+

Weill Medical College of Cornell University

Collaborator

Trials

1,103

Recruited

1,157,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

University of Miami

Collaborator

Trials

976

Recruited

423,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

University of California, San Diego

Collaborator

Trials

1,215

Recruited

1,593,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

Rosuvastatin is an effective statin that significantly improves lipid profiles in patients with dyslipidemias, outperforming other statins like atorvastatin, pravastatin, and simvastatin in achieving LDL-C goals after 12 weeks of treatment.

The treatment is generally well tolerated, with low incidences of serious side effects, such as myopathy and elevated CPK levels, making rosuvastatin a safe first-line option for managing cholesterol in both low- and high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a review of its use in the management of dyslipidemia. Scott, LJ., Curran, MP., Figgitt, DP.[2018]

Rosuvastatin is a highly potent statin that effectively inhibits cholesterol synthesis, showing up to a 65% reduction in LDL cholesterol in hypercholesterolemic patients during early-phase studies.

The drug selectively targets liver cells with minimal uptake in nonhepatic tissues, and it has low potential for metabolic interactions, making it a safe option for lipid-lowering therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the pharmacology of statins: characteristics of rosuvastatin. Chapman, MJ., McTaggart, F.[2019]

In the JUPITER trial, rosuvastatin significantly reduced the occurrence of major cardiovascular events in healthy individuals aged ≥60 years (women) or ≥50 years (men) with normal LDL-C levels but elevated hsCRP levels, demonstrating its efficacy in primary prevention of cardiovascular disease.

Rosuvastatin was well tolerated, with most side effects being mild to moderate, and it effectively lowered both LDL-C and hsCRP levels, although the exact mechanism of its benefits remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a review of its use in the prevention of cardiovascular disease in apparently healthy women or men with normal LDL-C levels and elevated hsCRP levels. Carter, NJ.[2015]

In a study of 502 patients with primary hypercholesterolemia, rosuvastatin (5 mg and 10 mg) significantly reduced LDL cholesterol levels by 42% and 49%, respectively, outperforming pravastatin and simvastatin, which reduced LDL-C by 28% and 37%.

Rosuvastatin 10 mg achieved National Cholesterol Education Program (NCEP) treatment goals in 87% of patients, demonstrating its superior efficacy compared to pravastatin (53%) and simvastatin (64%), while all treatments were well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin demonstrates greater reduction of low-density lipoprotein cholesterol compared with pravastatin and simvastatin in hypercholesterolaemic patients: a randomized, double-blind study. Paoletti, R., Fahmy, M., Mahla, G., et al.[2019]

Statins, or HMG-CoA reductase inhibitors, have been shown to be effective in managing dyslipidemia and improving liver function in patients with chronic liver diseases like nonalcoholic fatty liver disease and hepatitis C, based on a review of studies from 2005 to 2011.

Despite concerns about potential liver damage, clinical trials indicated that statin therapy did not lead to significant adverse effects and often resulted in improved liver enzyme levels and lipid profiles in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitor use in chronic liver disease: a therapeutic controversy. Tzefos, M., Olin, JL.[2022]

Rosuvastatin, currently in phase III clinical trials, shows promise in significantly lowering total cholesterol and LDL cholesterol levels in patients with high cholesterol, potentially more effectively than other statins.

However, there is not enough evidence to assess the safety of rosuvastatin or its impact on heart-related health outcomes, indicating that further research is needed to fully understand its benefits and risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin: do we need another statin? Ho, C.[2010]

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]

In a study involving 12,400 patients over 12,212 patient-years, rosuvastatin was found to have a safety profile similar to other statins, with adverse events occurring in 57.4% of patients, comparable to 56.8% in the placebo group.

Serious side effects like myopathy and significant liver or muscle enzyme elevations were very rare (less than 0.03% for myopathy), indicating that rosuvastatin is well tolerated among patients with dyslipidemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of rosuvastatin. Shepherd, J., Hunninghake, DB., Stein, EA., et al.[2015]

Rosuvastatin (Crestor) is more effective than other statins in lowering low-density lipoprotein cholesterol (LDL-C), showing greater reductions across doses of 5-40 mg/day, and also increases high-density lipoprotein cholesterol while significantly reducing triglycerides.

In clinical trials, rosuvastatin was well tolerated with a low incidence of adverse events, demonstrating a safety profile similar to other statins, although long-term safety and effectiveness in preventing coronary events have not been established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a high-potency HMG-CoA reductase inhibitor. Lopez, LM.[2019]

Rosuvastatin is a potent statin that significantly reduces LDL cholesterol by 52-63% at doses of 10-40 mg, outperforming other statins like atorvastatin and simvastatin in lowering LDL levels.

It is well tolerated and has a safety profile similar to other statins, making it a suitable option for patients with dyslipidemia, including those with hypertriglyceridemia or diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin--a highly effective new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor: review of clinical trial data at 10-40 mg doses in dyslipidemic patients. Schuster, H.[2017]

Citations

1. New Zealand pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a review of its use in the management of dyslipidemia. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Optimizing the pharmacology of statins: characteristics of rosuvastatin. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a review of its use in the prevention of cardiovascular disease in apparently healthy women or men with normal LDL-C levels and elevated hsCRP levels. [2015]

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

Rosuvastatin demonstrates greater reduction of low-density lipoprotein cholesterol compared with pravastatin and simvastatin in hypercholesterolaemic patients: a randomized, double-blind study. [2019]

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

3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitor use in chronic liver disease: a therapeutic controversy. [2022]

6. Canada pubmed.ncbi.nlm.nih.gov

Rosuvastatin: do we need another statin? [2010]

7. Germany pubmed.ncbi.nlm.nih.gov

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

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

Safety of rosuvastatin. [2015]

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

Rosuvastatin: a high-potency HMG-CoA reductase inhibitor. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Rosuvastatin--a highly effective new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor: review of clinical trial data at 10-40 mg doses in dyslipidemic patients. [2017]