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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of Zurich
Sponsor:
Collaborators:
Swiss National Science Foundation
Novartis
Information provided by (Responsible Party):
University of Zurich
ClinicalTrials.gov Identifier:
NCT01529554
First received: February 3, 2012
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

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).


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

Study Type: Interventional
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

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 ] [ 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 12-48h (baseline) and 30 days


Secondary Outcome Measures:
  • 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 12-48 h (baseline) and 30 days


Estimated Enrollment: 150
Study Start Date: May 2014
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: October 2015 (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

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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) within 24 hours of chest pain onset
  4. Age > 18 years
  5. 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. Major elective surgery planned in study period
  5. No informed consent
  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 ClinicalTrials.gov identifier: NCT01529554

Contacts
Contact: Roland Klingenberg, MD 0041 44 255 ext 1111 roland.klingenberg@usz.ch

Locations
Switzerland
University Hospital Bern Not yet recruiting
Bern, Switzerland
Contact: Stephan Windecker, Professor         
Principal Investigator: Stephan Windecker, Professor         
University Hospital Geneva Not yet 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: Roland Klingenberg, MD    0041 44 255 ext 1111    roland.klingenberg@usz.ch   
Principal Investigator: Thomas F Lüscher, Professor         
Sub-Investigator: Roland Klingenberg, MD         
Sponsors and Collaborators
University of Zurich
Swiss National Science Foundation
Novartis
Investigators
Study Chair: Thomas F Lüscher, Professor Dept. Cardiology, University Hospital Zurich
Study Director: Roland Klingenberg, MD Dept. of Cardiology, University Hospital Zurich
  More Information

No publications provided

Responsible Party: University of Zurich
ClinicalTrials.gov Identifier: NCT01529554     History of Changes
Other Study ID Numbers: CLEVER-ACS
Study First Received: February 3, 2012
Last Updated: May 21, 2014
Health Authority: Switzerland: Swissmedic

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

Additional relevant MeSH terms:
Inflammation
Myocardial Infarction
Ventricular Remodeling
Acute Coronary Syndrome
Pathologic Processes
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Pathological Conditions, Anatomical
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms
Everolimus
Sirolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents

ClinicalTrials.gov processed this record on July 31, 2014