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CirrhosisPhase 3SACREDNCT03654053

Multi-Center Study of the Effects of Simvastatin on Hepatic Decompensation and Death in Subjects Presenting With High-Risk Compensated Cirrhosis

A Phase 3 study testing Simvastatin 40mg in people with Cirrhosis, run by VA Office of Research and Development at 11 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase III, randomized, double-blind, placebo-controlled, multi-center study seeks to test whether simvastatin, a statin usually used to lower cholesterol to prevent heart problems and strokes, can lower the risk of hepatic decompensation (developing symptoms of cirrhosis) in U.S. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Cirrhosis
What is being tested?
Simvastatin 40mg
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
142 participants
Where
11 sitesUnited States
Study dates
2 Oct 2020to 31 Dec 2026
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • U.S. Veteran
  • Cirrhosis due to chronic viral hepatitis, or alcohol or non-alcoholic fatty liver
  • Compensated cirrhosis (history of endoscopically-confirmed variceal hemorrhage, absence of overt ascites, history of overt non-precipitated encephalopathy)
  • Age > 18 and <= 80
  • High risk of cirrhosis decompensation as defined by any of the following:
  • Presence of esophageal varices on endoscopy
Show all 11Show fewer
  • Presence of portosystemic collaterals on imaging as determined by a body radiologist
  • Fibroscan VCTE >= 20kPa
  • Platelet count <= 125 K/mm
  • 44 total points (~50% of clinically significant portal hypertension using the ANTICIPATE Nomogram)
  • Competent to provide informed consent

Who cannot join

  • Prior exposure to any statin within 6 months
  • Prior allergy or sensitivity to simvastatin
  • History of variceal hemorrhage confirmed endoscopically within the previous 3 years
  • Presence of overt ascites or treatment with diuretics for ascites with 6 months
  • History of chronic, recurrent or episodic overt hepatic encephalopathy with asterixis within 6 months
  • History of hepatocellular carcinoma
Show all 19Show fewer
  • Child-Turcotte-Pugh C Stage (CTP Score > 9)
  • Prior receipt of organ transplant
  • Participation in another pharmacological clinical trial within 3 months of the current study
  • Pregnancy or anticipated pregnancy within 2 years
  • Breast Feeding
  • Patients with life expectancy < 3 years due to comorbid conditions
  • Independent indication for initiation of statin therapy
  • Patients with any form of clinical atherosclerotic cardiovascular disease (ASCVD)
  • Patients with primary LDL-C < 190 mg/dl
  • Patients with diabetes mellitus, age 40-75 years, with LDL-C levels >=130 mg/dl
  • Need for concomitant administration of potent inhibitors of CYP34A4 enzymes (medications or other supplements that should not be taken with simvastatin, including cyclosporine, danazol, gemfibrozil, fenofibrate, extended release niacin, itraconazole, ketoconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, macrolide antibiotics - erythromycin, clarithromycin, telithromycin, nefazadone, amlodipine, verapamil, diltiazem, dronedarone, amiodarone, renolazine, lomitapide, and cobicistat)
  • Prior TIPSS shunt
  • Hemodialysis

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA

    Boston, Massachusetts, 02130

  • Brooklyn Campus of the VA NY Harbor Healthcare System, Brooklyn, NY

    Brooklyn, New York, 11209

  • Michael E. DeBakey VA Medical Center, Houston, TX

    Houston, Texas, 77030

  • Robley Rex VA Medical Center, Louisville, KY

    Louisville, Kentucky, 40206

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

    Philadelphia, Pennsylvania, 19104-4551

  • Philadelphia MultiService Center, Philadelphia, PA

    Philadelphia, Pennsylvania, 19106

  • Hunter Holmes McGuire VA Medical Center, Richmond, VA

    Richmond, Virginia, 23249

  • San Francisco VA Medical Center, San Francisco, CA

    San Francisco, California, 94121

  • VA Puget Sound Health Care System Seattle Division, Seattle, WA

    Seattle, Washington, 98108

  • James J. Peters VA Medical Center, Bronx, NY

    The Bronx, New York, 10468

  • VA Connecticut Healthcare System West Haven Campus, West Haven, CT

    West Haven, Connecticut, 06516

Other trials in United States

About this study

Official title: Effect of Simvastatin on Hepatic Decompensation and Death in Subjects With High-risk Compensated Cirrhosis

This phase III, randomized, double-blind, placebo-controlled, multi-center study seeks to test whether simvastatin, a statin usually used to lower cholesterol to prevent heart problems and strokes, can lower the risk of hepatic decompensation (developing symptoms of cirrhosis) in U.S. Veterans who have compensated cirrhosis (the liver is scarred and damaged but there are no symptoms). The study will also explore how changes or differences in genes effect the safety and effectiveness of using statins and how the use of statins affects quality of life.

Read the detailed description

HMG-coA reductase inhibitors (statins), independent of cholesterol-lowering effects, are beneficial in liver diseases by reducing endothelial dysfunction, intrahepatic vasoconstriction, inflammation and fibrosis, and can reduce portal vein blood pressure. Clinically significant portal hypertension (hepatic vein wedge pressure greater than or equal to 10mmHg) is the most important predictor of decompensation and death in patients with cirrhosis.

This randomized, double-blind, placebo-controlled, multi-center Phase III interventional study seeks to demonstrate that statin therapy in patients with cirrhosis at high-risk for hepatic decompensation will reduce the incidence of hepatic decompensation, hepatocellular carcinoma or all-cause mortality.

Patients with compensated cirrhosis at high-risk for hepatic decompensation will be stratified based on the presence or absence of varices and randomized to simvastatin 40mg/day for up to 24 months. Patients will be observed for the development of hepatic decompensation (variceal hemorrhage, ascites, encephalopathy), hepatocellular carcinoma, liver-related death, death from any cause, and/or complications of statin therapy. Additionally, the interaction of SLCO1B1 and KIF6 polymorphisms on safety and clinical efficacy of statin therapy and the impact of statin exposure on health-related quality of life in patients with compensated cirrhosis will be examined.

Conditions
Cirrhosis
Being tested
Placebo Oral Tablet, Simvastatin 40mg
Keywords
cirrhosis, hepatic decompensation, HMG-coA reductase, hepatocellular carcinoma, clinical trial, Human
Medical subject headings
Fibrosis, Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Placebo Oral TabletDrug

    Also called Placebo

    Placebo taken once nightly at bed time.

  • Simvastatin 40mgDrug

    Also called Simvastatin

    Simvastatin 40mg taken once nightly at bed time.

Study groups in NCT03654053
Study groupRoleWhat they receive
SimvastatinExperimentalSimvastatin 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.
Receives: Drug: Simvastatin 40mg
PlaceboPlacebo comparatorPlacebo 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.
Receives: Drug: Placebo Oral Tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Survival free from hepatic decompensation

    Occurrence of hepatic decompensation measured by first variceal hemorrhage, or development of ascites, or onset of hepatic encephalopathy, or hepatocellular carcinoma.

    Measured: 24 months

Secondary outcomes (7)

  1. Liver-related death

    Occurrence of death after hepatic decompensation, or hepatocellular carcinoma or transplantation

    Measured: 24 months

  2. Survival free from major cardiac events

    Occurrence of acute myocardial infarction, or unstable angina, or acute ischemic stroke, or coronary revascularization.

    Measured: 24 months

  3. Change in patient health-related quality of life

    Clinically significant change in score from baseline to month 12 as assessed by the PROMIS-29 questionnaire

    Measured: 12 months

  4. Statin-related hepatotoxicity

    Occurrence of hepatotoxicity defined as Grade 3 liver toxicity per CTCAE 5.0 ( 5 times upper limit of normal as defined by local laboratory- transaminases)

    Measured: 24 months

  5. Myositis

    Occurrence of myositis defined as either Grade 3 myositis (pain associated with severe weakness; limiting self care Activities Daily Living {ADL}) OR Grade 4 creatine phosphokinase by CTCAE 5.0 ( 10x upper limit of normal)

    Measured: 24 months

  6. Rhabdomyolysis

    Occurrence of rhabdomyolysis defined as Grade 3 (symptomatic, urgent intervention indicated)

    Measured: 24 months

  7. Hepatotoxicity

    Liver enzyme testing (AST, ALT, alkaline phosphatase, total bilirubin) at each study visit.

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2018
  2. Study start2 Oct 2020
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
142 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03654053
Sponsor's protocol ID
GAST-010-19F
Other IDs
VOCAL-001
Acronym
SACRED
Status last verified
Jan 2026
First submitted
28 Aug 2018
Last updated
7 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Deidentified data will be shared upon request following completion of a DUA for purposes of verification and meta-analysis.

Publications

  • Kaplan DE, Mehta R, Garcia-Tsao G, Albrecht J, Aytaman A, Baffy G, Bajaj J, Hernaez R, Hunt K, Ioannou G, Johnson K, Kanwal F, Lee TH, Monto A, Pandya P, Schaubel D, Taddei TH. SACRED: Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis: Statins and Cirrhosis: Reducing Events of Decompensation. Contemp Clin Trials. 2021 May;104:106367. doi: 10.1016/j.cct.2021.106367. Epub 2021 Mar 24.

    PubMed 33771685

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Simvastatin 40mg in people with Cirrhosis, run by VA Office of Research and Development at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 7 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Survival free from hepatic decompensation (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03654053, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2026.

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