COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01529554
Recruitment Status : Recruiting
First Posted : February 9, 2012
Last Update Posted : May 27, 2020
Swiss National Science Foundation
Information provided by (Responsible Party):
University of Zurich

Brief Summary:

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 (12-72 hours after percutaneous coronary intervention) to 30 days follow-up measured by MRI (Late Gadolinium Enhancement (LGE) for transmurality).

  2. (2° endpoint):

    To evaluate microvascular obstruction (MVO) as change from baseline (12-72 hours after percutaneous coronary intervention) to 30 days follow-up evaluated by MRI.

  3. (3° endpoints):

    1. Change of left ventricular volume from baseline (12-72 hours after percutaneous coronary intervention) to 30 days follow-up measured by MRI.
    2. 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).

Condition or disease Intervention/treatment Phase
Acute Coronary Syndromes Drug: Everolimus Drug: Placebo Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Actual Study Start Date : January 8, 2015
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack
Drug Information available for: Everolimus

Arm Intervention/treatment
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)
Drug: Everolimus
(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
Drug: Placebo
matched placebo tablets manufactured to be identical to verum tablets except content of everolimus

Primary Outcome Measures :
  1. Myocardial infarct size measured by MRI [ Time Frame: Change from baseline at 30 days ]
    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

Secondary Outcome Measures :
  1. Microvascular obstruction (MVO) measured by MRI [ Time Frame: Change from baseline at 30 days ]
    To evaluate microvascular obstruction (MVO) by MRI at 12-72 h (baseline) and 30 days

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Elevation Myocardial Infarction (STEMI) as defined by:

    • ST-Elevation > 1mm in > 2 leads OR
    • Novel left bundle branch block (LBBB) OR
    • Posterior MI with ST-Depression > 1mm in > 2 leads
  2. Chest pain duration of > 10 minutes
  3. Primary Coronary Intervention (PCI) with drug-eluting stent (DES) within 24 hours of chest pain onset in the occluded culprit artery
  4. First Myocardial Infarction
  5. Occluded coronary artery at angiography specifically occlusion of one coronary vessel in the proximal third of either LAD, RCX or RCA, the mid segment of right coronary artery (RCA) or mid segment of a large left anterior descending (LAD) coronary artery, i.e. when the latter reaches the apex.
  6. Male and female patients 18 years to 90 years of age
  7. Signed informed consent

Exclusion Criteria:

  1. Participation in another drug or stent trial
  2. Pregnant women or nursing mothers
  3. Mechanical complication during acute coronary syndrome
  4. Scheduled PCI for additional lesion within 30 days
  5. Multivessel disease
  6. Major elective surgery planned in trial period
  7. Malignancy (unless healed or remission > 5 years)
  8. Chronic infection (HIV, Tbc, empyema)
  9. Severely compromised renal function (GFR< 30 ml/min)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01529554

Layout table for location contacts
Contact: Barbara Stähli, MD, eMBA

Layout table for location information
Kerckhoff-Klinik, Department of Cardiology Not yet recruiting
Bad Nauheim, Germany
Contact: Roland Klingenberg, MD   
Principal Investigator: Roland Klingenberg, MD         
University Hospital Chartié Not yet recruiting
Berlin, Germany
Contact: Ulf Landmesser, MD   
Principal Investigator: Ulf Landmesser, Professor         
University Hospital Mainz Not yet recruiting
Mainz, Germany
Contact: Thomas Münzel, MD   
Principal Investigator: Thomas Münzel, Professor         
University Hospital Bern Recruiting
Bern, Switzerland
Contact: Stephan Windecker, Professor   
Principal Investigator: Stephan Windecker, Professor         
University Hospital Geneva Recruiting
Geneva, Switzerland
Contact: Francois Mach, Professor   
Principal Investigator: Francois Mach, Professor         
Cardiocentro Ticino Recruiting
Lugano, Switzerland
Contact: Tiziano Moccetti, Professor         
Principal Investigator: Tiziano Moccetti, Professor         
University Hospital Zurich Recruiting
Zurich, Switzerland
Contact: Barbara Stähli, MD, eMBA   
Principal Investigator: Barbara Stähli, MD, eMBA         
Sponsors and Collaborators
University of Zurich
Swiss National Science Foundation
Layout table for investigator information
Study Director: Frank Ruschitzka, Professor UniversityHospitalZurich
Layout table for additonal information
Responsible Party: University of Zurich Identifier: NCT01529554    
Other Study ID Numbers: CLEVER-ACS
First Posted: February 9, 2012    Key Record Dates
Last Update Posted: May 27, 2020
Last Verified: May 2020
Keywords provided by University of Zurich:
Acute Coronary Syndromes
ST-Elevation Myocardial Infarction
Infarct size
Additional relevant MeSH terms:
Layout table for MeSH terms
Acute Coronary Syndrome
ST Elevation Myocardial Infarction
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Myocardial Infarction
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs