Background: Recent studies report that intracoronary administration of autologous bone marrow mononucleated cells (BM-MNCs) may improve remodeling of the left ventricle after acute myocardial infarction (AMI). Subgroup analysis suggest that early treatment between days 4 and 7 after AMI is probably most effective; however, the optimal time point of intracoronary cell administration has never been addressed in clinical trials. Furthermore, reliable clinical predictors are lacking for identifying patients who are thought to have most benefit from cellular therapy.
Study design: In a multicenter trial, 192 patients with AMI successfully treated by percutaneous coronary intervention (PCI) of the infarct-related artery will be randomized in a 1:1:1 pattern to 1 control and 2 BM-MNC treatment groups. The control group will be treated with state-of-the-art medical management. The treatment groups will receive intracoronary administration of autologous BM-MNC at 5 to 7 days or 3 to 4 weeks after the initial event, respectively. Left ventricular function as well as scar size, transmural extension, and regional wall motion score will be assessed by cardiac magnetic resonance (CMR) studies at baseline and after 4 and 12 months.
Methods: Fifty milliliters of bone marrow will be harvested by aspiration from the iliac crest and then carried by courier to a centralized cell processing facility. The mononucleated cell fraction will be isolated by density gradient centrifugation, washed, and resuspended in 10 mL of injection medium. The cells will be characterized by fluorescence-activated cell sorting analysis and tested for sterility and potency both "in vitro" and "in vivo." Bone marrow MNC will then be reinfused directly in the infarct-related coronary artery.
End points: The primary end point is the change in global left ventricular (LV) ejection fraction by CMR at 4 months as compared to baseline. Comparisons will then be made between each of the prespecified therapy subgroups (early and late after AMI) and the control group. Secondary end points include change in infarct size, change in regional myocardial thickness, and wall motion at 4 and 12 months compared to baseline. Infarct extension (size and transmural extension), time delay to PCI, and coronary flow characteristics after PCI will be assessed as potential predictors of LV remodeling and change after cell therapy. Major adverse cardiac events (MACE) (death, myocardial infarction, coronary revascularization, rehospitalization for heart failure) will be assessed at 4, 12, and 24 months and time to MACE will be estimated.
Discussion: With the present study, we aim to determine the optimal time point of intracoronary administration of autologous BM-MNC after AMI on LV remodeling.
Trial registration: ClinicalTrials.gov NCT00355186.
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