STem cElls Mobilization in Acute Myocardial Infarction Outcome Trial

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate that granulocyte colony-stimulating factor (G-CSF) therapy in addition to state-of-the-art treatment (pharmacological and non pharmacological) is safe and significantly improves clinical outcome in patients with reduced left ventricular ejection fraction (LVEF) (≤45%) after successful reperfusion for large anterior acute myocardial infarction.

Detailed Description
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Post infarction heart failure (HF) remains a major cause of morbidity and mortality. In the United States, more than three million patients, and 700.000 in Italy, have cardiac failure and its most common cause is ischemic heart disease. The major goal to improve post infarction LV function would be the stimulation of neovascularization and the enhancement of regeneration of cardiac myocytes within the infarcted area. Recent experimental studies suggest that bone marrow-derived progenitor cells (BMCs) or circulating endothelial progenitor cells (cEPCs) contribute to the regeneration of infarcted myocardium, to enhance neovascularization of ischemic myocardium, to prevent cardiomyocyte apoptosis, to alter scar formation by reducing the development of myocardial fibrosis and, thereby, to improve cardiac function. G-CSF is a hematopoietic cytokine produced by monocytes, fibroblasts and endothelial cells. G-CSF is known to have multiple functions in normal, steady-state hematopoiesis. It is routinely used to mobilize CD34+ hematopoietic stem cells from the BM into peripheral blood, thus enabling their easier collection compared to BM aspirate procedure. The proven efficacy and safety of G-CSF, both in healthy donors and patients with haematological disease, along with favourable results from studies of CD34+ cell transplantation in patients with MI or ischemia, suggest that G-CSF based BMC transplantation may have an efficacy in patients with MI.

Official Title
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Phase III Study on STem cElls Mobilization in Acute Myocardial Infarction

Conditions
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Anterior Acute Myocardial Infarction, Left Ventricular Systolic Dysfunction

Intervention / Treatment
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* Drug: G-CSF administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients affected by acute anterior ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) or PCI-rescue with persistent occlusion of coronary artery, Time symptom-to-balloon (≥3 h and ≤12h or ≤24 h if symptoms persist), Thrombolysis in Myocardial Infarction (TIMI) flow post PCI ≥2, Evidence of left ventricular (LV) dysfunction (EF biplane ≤45%) ≤24 h after revascularization, Men and women aged ≥18 years and ≤75 years, Informed consent must be signed before proceeding with any study procedure. Exclusion Criteria: Previous anterior MI, Recent MI (within 1 month), Known previous LV dysfunction (EF <45%), Patients with angiographic evidence of coronary anatomy not suitable for PCI, or needing coronary artery bypass grafting (CABG), Valve disease requiring surgical correction, History of previous cardiac surgery or PCI on LAD within 6 months, Previous or current documented history of leukemia, myeloproliferative or myelodysplastic disorder, Previous or current documented history of malignant disease, Haemoglobin <10 mg/dl, White blood cells (WBC) >25.000 mm3, Platelet <50.000 mm3, Sepsis, Known HIV infection, Immune system diseases, Interstitial lung disease Serious concomitant medical conditions (other than ischemic heart disease), Pregnancy and breast feeding, Documented alcohol and drug abuse, Anticipated poor compliance. Current participation in a clinical trial with other investigational products Other cell therapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: G-CSF administration<br>Granulocyte Colony-Stimulating Factor (G-CSF) administration - 5 microg/kg subcutaneous every 12 hours for 6 days | Drug: G-CSF administration<br>* Zarzio - 5 microg/kg bis in die for 6 days<br>* Other names: Zarzio;|
| No Intervention: standard therapy<br>Standard therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The composite endpoint of: - All cause death or, - recurrence of myocardial infarction (MI) or, - hospitalization due to heart failure. |  | two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - All cause death and cardiovascular events | The following Cardiovascular events will be assessed: recurrence of MI, hospitalization due to heart failure, cardiovascular death, coronary revascularization, fatal and non fatal stroke, hospitalization due to any cause, cardiovascular hospitalization, resuscitation and/or appropriate automated implanted cardioverter defibrillator(AICD) therapy. | two years |