SACRED: Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis: Statins and Cirrhosis: Reducing Events of Decompensation

David E. Kaplan, Rajni Mehta, Guadalupe Garcia-Tsao, Jeffrey Albrecht, Ayse Aytaman, Gyorgy Baffy, Jasmohan Bajaj, Ruben Hernaez, Kristel Hunt, George Ioannou, Kay Johnson, Fasiha Kanwal, Tae Hoon Lee, Alexander Monto, Prashant Pandya, Douglas Schaubel, Tamar H. Taddei

Research output: Contribution to journalArticlepeer-review

Abstract

Background/Aims: The development of decompensation in cirrhosis demarcates a marked change in the natural history of chronic liver disease. HMG-CoA reductase inhibitors (statins) exert pleiotropic effects that reduce inflammation and fibrosis as well as improve vascular reactivity. Retrospective studies uniformly have associated statin utilization with improved outcomes for patients with cirrhosis. Prospective human studies have shown that statins reduce portal hypertension and reduce death in patients with decompensated cirrhosis after variceal hemorrhage when added to standard therapy with an acceptable safety profile. This proposal aims to extend these findings to demonstrate that simvastatin reduces incident hepatic decompensation events among cirrhotic patients at high risk for hepatic decompensation. Methods: We will perform the SACRED Trial (NCT03654053), a phase III, prospective, multi-center, double-blind, randomized clinical trial at 11 VA Medical Centers. Patients with compensated cirrhosis with clinically significant portal hypertension will be stratified based upon the concomitant use of nonselective beta-blockers and randomized to simvastatin 40 mg/day versus placebo 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. Ancillary studies will evaluate patient-reported outcomes and pharmacogenetic corollaries of safety and/or efficacy. Conclusion: Statins have a long track-record of safety and tolerability. This class of medications is generic and inexpensive, and thus, if the hypothesis is proven, there will be few barriers to widespread acceptance of the role of statins to prevent decompensation in patients with compensated cirrhosis. ClinicalTrials.gov Identifier: NCT03654053

Original languageEnglish (US)
Article number106367
JournalContemporary Clinical Trials
Volume104
DOIs
StatePublished - May 1 2021

Bibliographical note

Funding Information:
United States Department of Veterans Affairs CSR&D Merit Review I01-CX002010. The sponsor had no role in the design of the clinical trial and will play no role in data collection, analysis, interpretation, writing or publication.

Publisher Copyright:
© 2021

Keywords

  • Cirrhosis
  • Clinical trial
  • HMG-CoA reductase inhibitor
  • Human
  • Prospective
  • Veterans

PubMed: MeSH publication types

  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

Fingerprint

Dive into the research topics of 'SACRED: Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis: Statins and Cirrhosis: Reducing Events of Decompensation'. Together they form a unique fingerprint.

Cite this