Liver Cirrhosis Network Rosuvastatin Efficacy and Safety for Cirrhosis in the United States

NCT05832229 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: Pro000705805U24DK130164-04
• Study Type: interventional
• Target: 256
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

Cirrhosis; Cirrhosis, Liver; Cirrhosis Early; Cirrhosis Due to Hepatitis B; Cirrhosis Advanced; Cirrhosis Infectious; Cirrhosis Alcoholic; Cirrhosis Due to Hepatitis C

Keywords

Cirrhosis; Liver; Nonalcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (1)

• Mean change in liver stiffness

  Mean change in liver stiffness as measured in kilopascal with Vibration-Controlled Transient Elastography between study entry and week 96. Range: 2 to 75 kilopascal. Higher stiffness indicates increased disease progression

  96 weeks

Secondary Outcomes (18)

• Time to disease progression

  96 weeks

• All-cause mortality

  96 weeks

• Time to development of ascites

  96 weeks

• Time to development of overt hepatic encephalopathy

  96 weeks

• Time to development of variceal bleed

  96 weeks

Study Arms (2)

Active

EXPERIMENTAL

Open-label lead-in period of 4 weeks on 20 mg (10 mg for participants of East ancestry or on a protease inhibitor) 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 or on a protease inhibitor).

Drug: Rosuvastatin

Placebo

PLACEBO COMPARATOR

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

Drug: Rosuvastatin

Interventions

Rosuvastatin DRUG

Patients meeting all eligibility criteria will be assigned to a randomization arm prior to initiation of a 4-week lead-in phase of the study. All participants will undergo a 4-week, open-label active run-in phase to evaluate initial safety and adherence to rosuvastatin. During this active run-phase, all participants will receive target dose rosuvastatin-- 20 mg daily (10 mg daily for participants of East-Asian ancestry or on a protease inhibitor). After the active run-in phase, all participants will continue with their pre-assigned randomization (1:1) treatment of rosuvastatin 20 mg daily (10 mg daily for participants of East-Asian ancestry or on a protease inhibitor) or matching placebo.

Also known as: Rosuvastatin 20 mg, Rosuvastatin 10 mg

Active; Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years
• Cirrhosis due to nonalcoholic steatohepatitis, alcohol-associated liver disease, or chronic viral hepatitis (treated hepatitis B virus or hepatitis C virus)
• Clinical diagnosis of cirrhosis as defined investigator confirmation and the following:
• At least one liver biopsy within 5 years prior to consent showing either: Metavir stage 4 fibrosis; Ishak Stage 5-6 fibrosis, OR
• At least 2 of the following:
• i. Evidence on imaging: Nodular liver with either splenomegaly or recanalized umbilical vein within the past 48 weeks ii. Liver stiffness: vibration-controlled transient elastography within 48 weeks prior to consent or during Screening ≥15 kilopascal or magnetic resonance elastography within 48 weeks prior to consent or during Screening ≥5 kilopascal iii. Evidence of varices demonstrated on imaging or endoscopy within 3 years prior to consent or during Screening iv. Either: Fibrosis-4\>2.67 or platelets \<150/mL within 6 months prior to consent or during Screening
• Two measures of vibration-controlled transient elastography: one at screening and one at the randomization study visit, meeting the following criteria:
• The first measure must be ≥ 15 kilopascal.
• The two measures must be at least 2 hours apart and no more than 60 days apart from one another.
• The mean of two measurements must be ≥ 15 kilopascal.
• Additionally, both screening and open-label dispense liver stiffness measures must be ≤50 kPa
• Compensated defined by:
• Absence of ascites/hydrothorax, hepatic encephalopathy or variceal bleeding currently or in the last 48 weeks, as determined clinically by investigator.
• If prior history of decompensation, must be without current symptoms of decompensation and no longer requiring treatment of complications for the last 48 weeks, including the use of diuretics for the treatment of ascites, and/or rifaximin or lactulose for the treatment of hepatic encephalopathy. Use of non-selective beta blockers will be allowed.
• Child-Pugh score \<8

You may not qualify if:

• Currently on a statin or any statin exposure within 24 weeks prior to consent.
• Known indication for statin therapy, defined as:
• Prior peripheral vascular, cardiovascular or cerebrovascular event for which statins are indicated for secondary prevention, OR
• Documented familial hypercholesterolemia, heterozygous familial hypercholesterolemia, OR
• Fasting LDL-C ≥ 190 mg/dL
• Myocardial infarction, Unstable angina, transient ischemic events, or stroke within 24 weeks of screening.
• Alcohol Use Disorder Identification Test (AUDIT) total score of ≥8 at screening.
• Patients with limitations in attending study visits.
• Prisoners.
• Known prior or current hepatocellular carcinoma (HCC) or cholangiocarcinoma.
• Known transjugular intrahepatic portosystemic shunt (TIPS), balloon retrograde transvenous obliteration (BRTO) or porto-systemic shunt surgery regardless of time of occurrence.
• Current (in past 24 weeks prior to consenting) use of medications known to cause hepatic fibrogenesis or confound endpoint assessment, defined as:
• amiodarone
• methotrexate
• warfarin

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• The Cleveland Clinic: collaborator
• Columbia University: collaborator
• Weill Medical College of Cornell University: collaborator
• Duke University: collaborator
• Mayo Clinic: collaborator
• University of Miami: collaborator
• University of Michigan: collaborator
• University of California, San Diego: collaborator
• University of California, San Francisco: collaborator
• LAC+USC Medical Center: collaborator
• Virginia Commonwealth University: collaborator
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator
• National Cancer Institute (NCI): collaborator
• University of Southern California: collaborator

Study Sites (13)

University of California San Diego NAFLD Research Center

La Jolla, California, 92035, United States

RECRUITING

Keck Medical Center of USC

Los Angeles, California, 90033, United States

RECRUITING

LAC + USC Medical Center

Los Angeles, California, 90033, United States

RECRUITING

UCSF/Zuckerberg San Francisco General Hospital and Trauma Center

San Francisco, California, 94110, United States

RECRUITING

UCSF Medical Center

San Francisco, California, 94143, United States

RECRUITING

University of Miami Health System

Miami, Florida, 33122, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48109, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55901, United States

RECRUITING

New York Presbyterian/Weill Cornell

New York, New York, 10021, United States

RECRUITING

Columbia University Iriving School of Medicine

New York, New York, 10031, United States

RECRUITING

Duke Liver Center

Durham, North Carolina, 27710, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44192, United States

RECRUITING

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

RECRUITING

Related Links

• Information about the study

MeSH Terms

Conditions

Fibrosis; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Non-alcoholic Fatty Liver Disease

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Diseases; Digestive System Diseases; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Fatty Liver

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Abigail Smith, PhD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Crystal Santillanes, MS

CONTACT

312-503-5536; lcn@northwestern.edu

Mary Beth Tull, MBA, CCRP

CONTACT

312-503-4746; mary.tull@northwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The drug manufacturer and bottler will be unblinded, as will a few members of the Scientific and Data Coordinating Center. All other study team members will remain blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: This study is a randomized, double-blind, placebo-controlled Phase 2 clinical trial, of 20mg (or 10mg for participants of East Asian ancestry) of rosuvastatin by mouth, once daily. Participants will be randomized (1:1) to either once daily placebo or once daily rosuvastatin.

Study Record Dates

• First Submitted: March 24, 2023
• First Posted: April 27, 2023
• Study Start: December 7, 2023
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): August 31, 2029
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF

Locations

US (13)