Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients with ST-segment Elevation Myocardial Infarction and Left Ventricular Dysfunction: A Multicenter Randomized, Double-Blind and Placebo-Controlled Clinical Trial

RATIONALE:Allogeneic cardiac stem cells (AlloCSC-01) have shown protective, immunoregulatory and regenerative properties with a robust safety profile in large animal models of heart disease. OBJECTIVE:To investigate the safety and feasibility of early administration of AlloCSC-01 in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS:CAREMI was a phase I/II multicenter, randomized, double-blind, placebocontrolled trial in patients with STEMI, LVEF ≤ 45% and infarct size ≥ 25% of left ventricular (LV) mass by cardiac magnetic resonance (MR), who were randomized (2:1) to receive AlloCSC-01 or placebo through the intracoronary route at day 5-7. The primary endpoint was safety and included all-cause death and major adverse cardiac events at 30 days (MACEall-cause death, reinfarction, hospitalization due to heart failure, sustained ventricular tachycardia, ventricular fibrillation and stroke). Secondary safety endpoints included MACE at 6 and 12 months, adverse events (AE) and immunological surveillance. Secondary exploratory efficacy endpoints were changes in infarct size (% LV mass) and indices of ventricular remodeling by MR at 12 months. Forty-nine patients were included (92% male, 55±11 years), 33 randomized to AlloCSC-01 and 16 to placebo. No deaths or MACE were reported at 12 months. One severe AE in each group was considered possibly related to study treatment (allergic dermatitis and rash). AlloCSC-01 elicited low levels of donor specific antibodies in 2 patients. No immune-related AE were found and no differences between groups were observed in MR-based efficacy parameters at 12 months. The estimated treatment effect of AlloCSC-01 on the absolute change from baseline in infarct size was -2.3% (95%CI -6.5 to 1.9%). CONCLUSIONS:Allogeneic cardiac stem cells can be safely administered in STEMI patients with LV dysfunction early after revascularization. Low immunogenicity and absence of immune-mediated events will facilitate adequately powered studies to demonstrate their clinical efficacy in this setting. CLINICAL TRIAL REGISTRATION:NCT 02439398.