Multi-Center Study of the Effects of Simvastatin on Hepatic Decompensation and Death in Subjects Presenting With High-Risk Compensated Cirrhosis
SACRED
Effect of Simvastatin on Hepatic Decompensation and Death in Subjects With High-risk Compensated Cirrhosis
2 other identifiers
interventional
142
1 country
11
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Oct 2020
Longer than P75 for phase_3
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 28, 2018
CompletedFirst Posted
Study publicly available on registry
August 31, 2018
CompletedStudy Start
First participant enrolled
October 2, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2026
January 7, 2026
January 1, 2026
6.2 years
August 28, 2018
January 6, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (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.
24 months
Secondary Outcomes (7)
Liver-related death
24 months
Survival free from major cardiac events
24 months
Change in patient health-related quality of life
12 months
Statin-related hepatotoxicity
24 months
Myositis
24 months
- +2 more secondary outcomes
Study Arms (2)
Simvastatin
EXPERIMENTALSimvastatin 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.
Placebo
PLACEBO 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.
Interventions
Simvastatin 40mg taken once nightly at bed time.
Eligibility Criteria
You may qualify if:
- 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
- Presence of portosystemic collaterals on imaging as determined by a body radiologist
- Fibroscan VCTE \>= 20kPa
- Platelet count \<= 125 K/mm
- total points (\~50% of clinically significant portal hypertension using the ANTICIPATE Nomogram)
- Competent to provide informed consent
You may not qualify if:
- 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
- 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
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
San Francisco VA Medical Center, San Francisco, CA
San Francisco, California, 94121, United States
VA Connecticut Healthcare System West Haven Campus, West Haven, CT
West Haven, Connecticut, 06516, United States
Robley Rex VA Medical Center, Louisville, KY
Louisville, Kentucky, 40206, United States
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Boston, Massachusetts, 02130, United States
Brooklyn Campus of the VA NY Harbor Healthcare System, Brooklyn, NY
Brooklyn, New York, 11209, United States
James J. Peters VA Medical Center, Bronx, NY
The Bronx, New York, 10468, United States
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
Philadelphia, Pennsylvania, 19104-4551, United States
Philadelphia MultiService Center, Philadelphia, PA
Philadelphia, Pennsylvania, 19106, United States
Michael E. DeBakey VA Medical Center, Houston, TX
Houston, Texas, 77030, United States
Hunter Holmes McGuire VA Medical Center, Richmond, VA
Richmond, Virginia, 23249, United States
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Seattle, Washington, 98108, United States
Related Publications (1)
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.
PMID: 33771685BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
David E. Kaplan, MD MSc
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Masking Details
- Double-blind, placebo-controlled
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- FED
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 28, 2018
First Posted
August 31, 2018
Study Start
October 2, 2020
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
December 31, 2026
Last Updated
January 7, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- Following closure of study database
- Access Criteria
- Data use / data transfer agreement
Deidentified data will be shared upon request following completion of a DUA for purposes of verification and meta-analysis.