Rationale and design of ApoA-I Event Reducing in Ischemic Syndromes II (AEGIS-II): A phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group study to investigate the efficacy and safety of CSL112 in subjects after acute myocardial infarction.

Abstract

Acute myocardial infarction (MI) patients remain at high risk for recurrent events. Cholesterol efflux, mediated by apolipoprotein A-I, removes excess cholesterol from atherosclerotic plaque and transports it to the liver for excretion. Impaired cholesterol efflux is associated with higher cardiovascular (CV) event rates among both patients with stable coronary artery disease and recent MI. CSL112, a novel intravenous formulation of apolipoprotein A-I (human) derived from human plasma, increases cholesterol efflux capacity. AEGIS-II is a phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial investigating the efficacy and safety of CSL112 compared to placebo among high-risk acute MI participants. Eligibility criteria include age ≥ 18 years with type 1 (spontaneous) MI, evidence of multivessel stable coronary artery disease, and presence of diabetes requiring pharmacotherapy, or ≥2 of the following: age ≥ 65 years, prior MI, or peripheral artery disease. A target sample of 17,400 participants will be randomized 1:1 to receive 4 weekly infusions of CSL112 6 g or placebo, initiated prior to or on the day of discharge and within 5 days of first medical contact. The primary outcome is the time to first occurrence of the composite of CV death, MI, or stroke through 90 days. Key secondary outcomes include the total number of hospitalizations for coronary, cerebral, or peripheral ischemia through 90 days and time to first occurrence of the composite primary outcome through 180 and 365 days. AEGIS-II will be the first trial to formally test whether enhancing cholesterol efflux can reduce the rate of recurrent major adverse CV events.

• Authors: C Michael Gibson, John J P Kastelein, Adam T Phillips, Philip E Aylward, Megan K Yee, Michal Tendera, Stephen J Nicholls, Stuart Pocock, Shaun G Goodman, John H Alexander, A Michael Lincoff, Christoph Bode, Danielle Duffy, Mark Heise, Gail Berman, Sojaita Jenny Mears, Pierluigi Tricoci, Lawrence I Deckelbaum, P Gabriel Steg, Paul Ridker, Roxana Mehran
• Journal: American heart journal (Am Heart J) Vol. 231 Pg. 121-127 (01 2021) ISSN: 1097-6744 [Electronic] United States
• PMID: 33065120 (Publication Type: Clinical Trial Protocol, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Cholesterol
• CSL112
• Lipoproteins, HDL
• Placebos

Topics

• Aged
• Humans
• Brain Ischemia (prevention & control)
• Cholesterol (metabolism)
• Coronary Artery Disease (metabolism)
• Diabetes Mellitus (drug therapy)
• Double-Blind Method
• Drug Administration Schedule
• Hospitalization (statistics & numerical data)
• Ischemia (prevention & control)
• Lipoproteins, HDL (administration & dosage, adverse effects, therapeutic use)
• Liver (metabolism)
• Myocardial Infarction (prevention & control, therapy)
• Myocardial Ischemia (prevention & control)
• Peripheral Vascular Diseases (prevention & control)
• Placebos (therapeutic use)
• Plaque, Atherosclerotic (metabolism)
• Stroke (prevention & control)
• Time Factors
• Multicenter Studies as Topic
• Clinical Trials, Phase III as Topic
• Randomized Controlled Trials as Topic