Controlled Level EVERolimus in Acute Coronary Syndromes (CLEVER-ACS)

Acute myocardial infarction (AMI) constitutes the major cause of death in most nations and death rates and morbidity remain substantial in the years thereafter. Inflammation is a hallmark throughout the distinct stages of atherosclerotic lesion formation preceding AMI as well as at the time of plaque rupture and during the post-infarct repair phase. Harnessing its harmful consequences constitutes an attractive therapeutic approach to address this unmet medical need.

The objectives of this study are to evaluate the effects of mTOR inhibition (everolimus) on infarct size, myocardial function and inflammation in patients with ST-Elevation Myocardial Infarction.

The efficacy objectives are:

1. (1° endpoint): To assess the effect of mTOR inhibition (everolimus) on myocardial infarct size as change from baseline measured by MRI (Late Gadolinium Enhancement for transmurality) at 12-48h (baseline) and 30 days
2. (2° endpoint): To evaluate microvascular obstruction (MVO) as change from baseline measured by MRI at 12-48 h (baseline) and 30 days

3. (3° endpoints):

   1. To determine the effect of mTOR inhibition (everolimus) as change from baseline on the classic biomarkers hsTnT, NT-proBNP, hs-CRP and IL-6 at 30 days compared to 12-48 h (baseline) and time-course (AUC)
   2. To evaluate the effect of mTOR inhibition (everolimus) on the inflammatory biomarkers as change from baseline for OPG, sRANKL, OPN at 30 days compared to 12-48 h (baseline) and time-course (AUC)
   3. Left ventricular volumes evaluated by MRI

The safety objectives are:

To explore the effect of mTOR inhibition (everolimus) on several clinical and safety laboratory parameters including plasma lipid levels and blood count. This will be complemented by analysis of inflammatory cell subsets in coronary thrombi and peripheral blood (CD4+ T helper lymphocyte subsets, monocyte subsets).