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:
To assess the effect of mTOR inhibition (everolimus) on myocardial infarct size as change from baseline (12-72 hours after percutaneous coronary intervention) to 30 days follow-up measured by MRI (Late Gadolinium Enhancement (LGE) for transmurality).
To evaluate microvascular obstruction (MVO) as change from baseline (12-72 hours after percutaneous coronary intervention) to 30 days follow-up evaluated by MRI.
- Change of left ventricular volume from baseline (12-72 hours after percutaneous coronary intervention) to 30 days follow-up measured by MRI.
- Change of biomarkers from time of coronary angiography to 30 days follow-up including a time-course (AUC). Biomarkers comprise hs-TnT, NT-proBNP, hs-CRP, IL-6 and inflammatory biomarkers OPG, sRANKL, OPN and CCN1.
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).
Acute Coronary Syndromes
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Phase I-II Randomized Prospective Double-blind Multi-center Trial on the Effects of a Short Course of Oral Everolimus on Infarct Size, Left Ventricular Remodeling and Inflammation in Patients With Acute ST-Elevation Myocardial Infarction|
- Myocardial infarct size measured by MRI [ Time Frame: Change from baseline at 30 days ] [ Designated as safety issue: No ]To assess the effect of mTOR inhibition (everolimus) on myocardial infarct size as measured by MRI (Late Gadolinium Enhancement (LGE) for infarct size (transmurality) at 12-72 h (baseline) and 30 days
- Microvascular obstruction (MVO) measured by MRI [ Time Frame: Change from baseline at 30 days ] [ Designated as safety issue: No ]To evaluate microvascular obstruction (MVO) by MRI at 12-72 h (baseline) and 30 days
|Study Start Date:||December 2014|
|Estimated Study Completion Date:||October 2016|
|Estimated Primary Completion Date:||October 2016 (Final data collection date for primary outcome measure)|
Active Comparator: Everolimus
Everolimus p.o. for 5 days (d0=7.5 mg, d1=7.5 mg, d2=7.5 mg, d3=5 mg, d4=5mg)
(d0=7.5 mg, d1=7.5 mg. d2=7.5 mg, d3=5 mg, d4=5mg)
Placebo Comparator: Placebo
Placebo comparator with identical composition of tablets except everolimus
matched placebo tablets manufactured to be identical to verum tablets except content of everolimus
Please refer to this study by its ClinicalTrials.gov identifier: NCT01529554
|Contact: Thomas F Lüscher, MD||0041 44 255 ext email@example.com|
|University Hospital Bern||Recruiting|
|Contact: Stephan Windecker, Professor|
|Principal Investigator: Stephan Windecker, Professor|
|University Hospital Geneva||Recruiting|
|Contact: Francois Mach, Professor|
|Principal Investigator: Francois Mach, Professor|
|Cardiocentro Ticino||Active, not recruiting|
|University Hospital Zurich||Recruiting|
|Contact: Thomas F Lüscher, MD firstname.lastname@example.org|
|Principal Investigator: Thomas F Lüscher, Professor|
|Sub-Investigator: Roland Klingenberg, MD|
|Study Chair:||Thomas F Lüscher, Professor||Dept. Cardiology, University Hospital Zurich|
|Study Director:||Roland Klingenberg, MD||Dept. of Cardiology, Kerckhoff-Klinik, Bad Nauheim, Germany|