TY - JOUR
T1 - SACRED
T2 - Effect of simvastatin on hepatic decompensation and death in subjects with high-risk compensated cirrhosis: Statins and Cirrhosis: Reducing Events of Decompensation
AU - Kaplan, David E.
AU - Mehta, Rajni
AU - Garcia-Tsao, Guadalupe
AU - Albrecht, Jeffrey
AU - Aytaman, Ayse
AU - Baffy, Gyorgy
AU - Bajaj, Jasmohan
AU - Hernaez, Ruben
AU - Hunt, Kristel
AU - Ioannou, George
AU - Johnson, Kay
AU - Kanwal, Fasiha
AU - Lee, Tae Hoon
AU - Monto, Alexander
AU - Pandya, Prashant
AU - Schaubel, Douglas
AU - Taddei, Tamar H.
N1 - 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
PY - 2021/5/1
Y1 - 2021/5/1
N2 - 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
AB - 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
KW - Cirrhosis
KW - Clinical trial
KW - HMG-CoA reductase inhibitor
KW - Human
KW - Prospective
KW - Veterans
UR - http://www.scopus.com/inward/record.url?scp=85103307128&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85103307128&partnerID=8YFLogxK
U2 - 10.1016/j.cct.2021.106367
DO - 10.1016/j.cct.2021.106367
M3 - Article
C2 - 33771685
AN - SCOPUS:85103307128
SN - 1551-7144
VL - 104
JO - Contemporary Clinical Trials
JF - Contemporary Clinical Trials
M1 - 106367
ER -
