COMPARE-AMI Trial: Comparison of Intracoronary Injection of CD133+ Bone Marrow Stem Cells to Placebo in Patients After Acute Myocardial Infarction and Left Ventricular Dysfunction: Study Rationale and Design

Abstract

Stem cell therapy has emerged as a promising approach to improve healing of the infarcted myocardium, to treat or prevent cardiac failure, and to restore lost cardiac function. Despite initial excitement, recent clinical trials using nonhomogenous human stem cells preparations showed variable results, raising concerns about the best cell type to transplant. Selected CD133(+) hematopoietic stem cells are promising candidate cells with great potential. COMPARE-acute myocardial infarction (AMI) study is a phase II, randomized, double-blind, placebo-controlled trial evaluating the safety and effectiveness of intracoronary CD133(+)-enriched hematopoietic bone marrow stem cells in patients with acute myocardial infarction and persistent left ventricular dysfunction. Patients who underwent successful percutaneous coronary intervention and present a persistent left ventricular ejection fraction <50% will be eligible to have bone marrow aspiration and randomized for intracoronary injection of selected CD 133(+) bone marrow cells vs placebo. The primary end point is a composite of a safety and efficacy end points evaluating the change at 4 months in the coronary atherosclerotic burden progression proximal and distal to the coronary stent in the infarct related artery; and the change in global left ventricular ejection fraction at 4 months relative to baseline as measured by magnetic resonance imaging. The secondary end point will be the occurrence of a major adverse cardiac event. To date, 14 patients were successfully randomized and treated without any protocol-related complication. COMPARE-AMI trial will help identify the effect of a selected population of the bone marrow stem cells on cardiac recovery of infarcted myocardium.

Improved Function and Myocardial Repair of Infarcted Heart by Intracoronary Injection of Mesenchymal Stem Cell-Derived Growth Factors

“…Using similar experimental protocol in the swine with 60-min LAD occlusion and reperfusion, Freyman and coworkers [40] demonstrated a reproducible infarction affecting 20-30% of the LV. The intracoronary route of administration of stem cells or growth factors has been demonstrated to be safe in clinical trial [48][49][50]. To our knowledge, this is the first study to investigate the paracrine and indirect effects of stem cell therapy by percutaneous intracoronary injection of MSC-derived growth factors for the treatment of acute myocardial ischemia in a pre-clinical large animal model.…”

Parameters influencing LVEF improvement with intracoronary bone marrow stem cell delivery in acute myocardial infarction

“…The improvement of LVEF seems to be higher in patients with lower baseline LVEF levels than those with a higher baseline level [2,3]. In particular, the patients whose baseline LVEF levels were lower than 45% had the most benefit from stem cells (Fig.…”

Use of Flow Cytometry for Quality Evaluation of Biomedical Cell Products

“…Например, имеются сообщения о результатах проведенных клинических исследований, свидетельствующие о том, что CD133 + ГСК после трансплантации улучшают функцию левого желудочка [36].…”