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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by University of Zurich
Swiss National Science Foundation
Information provided by (Responsible Party):
University of Zurich Identifier:
First received: February 3, 2012
Last updated: August 19, 2015
Last verified: August 2015

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 Intervention Phase
Acute Coronary Syndromes
Drug: Everolimus
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (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

Resource links provided by NLM:

Further study details as provided by University of Zurich:

Primary Outcome Measures:
  • 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:
  • 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

Estimated Enrollment: 150
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)
Arms Assigned Interventions
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


Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

Patients who enter the hospital with the main diagnosis of Acute Coronary Syndrome (STEMI) as defined by:

  1. 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
  6. Occlusion of coronary vessel in the proximal third of either LAD, RCX or RCA, 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
  7. Male and female patients 18 years to 90 years of age
  8. 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. Major elective surgery planned in study period
  6. Malignancy (unless healed or remission > 5 years)
  7. Chronic infection (HIV, Tbc, empyema)
  8. Severely compromised renal function (GFR< 30 ml/min)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01529554

Contact: Thomas F Lüscher, MD 0041 44 255 ext 2121

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 Active, not recruiting
Lugano, Switzerland
University Hospital Zurich Recruiting
Zurich, Switzerland
Contact: Thomas F Lüscher, MD   
Principal Investigator: Thomas F Lüscher, Professor         
Sub-Investigator: Roland Klingenberg, MD         
Sponsors and Collaborators
University of Zurich
Swiss National Science Foundation
Study Chair: Thomas F Lüscher, Professor Dept. Cardiology, University Hospital Zurich
Study Director: Roland Klingenberg, MD Dept. of Cardiology, Kerckhoff-Klinik, Bad Nauheim, Germany
  More Information

Responsible Party: University of Zurich Identifier: NCT01529554     History of Changes
Other Study ID Numbers: CLEVER-ACS
Study First Received: February 3, 2012
Last Updated: August 19, 2015

Keywords provided by University of Zurich:
Acute Coronary Syndromes
ST-Elevation Myocardial Infarction
Infarct size

Additional relevant MeSH terms:
Myocardial Infarction
Acute Coronary Syndrome
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents processed this record on May 25, 2017