THE IMPACT-CABG TRIAL: A CANADIAN RCT OF CD133+ STEM CELL THERAPY FOR ISCHEMIC CARDIOMYOPATHY

BACKGROUND: The IMPACT-CABG trial (NCT01033617) is a Canadian multicenter randomized, prospective, doubleblinded study investigating the feasibility, safety and efficacy of intramyocardial injections of autologous CD133+ stem cells in patients with chronic ischemic cardiomyopathy and impaired LV dysfunction (LVEF 25-45%) undergoing isolated CABG surgery. The primary safety endpoint was freedom from major adverse cardiac event (MACE) at time of injection and 6 months follow-up, including freedom from cardiac death, myocardial infarction (MI), repeat revascularization or severe arrhythmias. The secondary efficacy endpoint was regional myocardial perfusion and function assessed by magnetic resonance imaging (MRI). Herein we are reporting the safety results. METHODS: After an initial 5 (Montreal) or 2 (Toronto) openlabel patients who received stem cells, patients were then randomized in a 1:1 (Toronto1⁄418) or 2:1 (Montreal1⁄415) ratio to receive either stem cells or placebo. All forty patients (20 each in Montreal and Toronto) with ischemic cardiomyopathy and clinical indications for CABG provided informed consent and were assessed with preoperative stress echo and perfusion MRI. All patients had 100-150 cc of bone marrow aspirated from the iliac crest under local anaesthesia and light sedation on the morning of surgery. Stem cells were isolated using the CliniMACS CD133+ Reagent System (Miltenyi Biotec), which utilizes superparamagnetic beads composed of iron-dextran particles conjugated to monoclonal antibodies. On the afternoon following cell preparation, patients underwent conventional CABG surgery under cardiopulmonary bypass. Following the completion of the distal coronary anastomoses, the cell preparation containing up to 10 million cells or placebo was injected (10-15 injection sites) into the infarct and border zone as identified by MRI. RESULTS: Patient demographics, intraoperative data and hospital outcomes are presented in Table 1 for all 40 patients. Stem cell isolation procedures yielded cell preparations meeting release criteria in all patients randomized to cell delivery. There was no in-hospital mortality. No patient had a perioperative MI, 4 had renal failure, one had a wound infection and one had a seizure. During the 6-month followup period, one patient died from a pulmonary embolus, and no other MACE. CONCLUSION: This work represents the first Canadian experience with CD133+ stem cells for the treatment of chronic ischemic cardiomyopathy. There were no protocol-related complications, demonstrating that same-day isolation and delivery of stem cells in conjunction with CABG is safe and feasible. Cell therapy may become a valuable adjunct treatment for myocardial repair in heart failure patients in whom conventional therapies for ventricular dysfunction are limited.