Nicolas Noiseux1, Samer Mansour2, Richard Weisel3, Louis-Mathieu Stevens4, Shant Der Sarkissian5, Katherine Tsang3, Andrew M Crean6, Eric Larose7, Shu-Hong Li3, Bernd Wintersperger6, Minh Quan Vu8, Ignacio Prieto9, Ren-Ke Li3, Denis Claude Roy10, Terrence M Yau11. 1. Division of Cardiac Surgery, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada; Centre Hospitalier de l'Université de Montréal Research Center (CRCHUM), Montréal, Québec, Canada; Department of Surgery, Université de Montréal, Montréal, Québec, Canada. Electronic address: noiseuxn@videotron.ca. 2. Centre Hospitalier de l'Université de Montréal Research Center (CRCHUM), Montréal, Québec, Canada; Division of Cardiology, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada; Department of Medicine, Université de Montréal, Montréal, Québec, Canada. 3. Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada; Division of Cardiovascular Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. 4. Division of Cardiac Surgery, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada; Centre Hospitalier de l'Université de Montréal Research Center (CRCHUM), Montréal, Québec, Canada; Department of Surgery, Université de Montréal, Montréal, Québec, Canada. 5. Centre Hospitalier de l'Université de Montréal Research Center (CRCHUM), Montréal, Québec, Canada; Department of Surgery, Université de Montréal, Montréal, Québec, Canada. 6. Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada; Division of Medical Imaging, University of Toronto, Toronto, Ontario, Canada. 7. Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec City, Québec, Canada. 8. Centre Hospitalier de l'Université de Montréal Research Center (CRCHUM), Montréal, Québec, Canada. 9. Division of Cardiac Surgery, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada; Department of Surgery, Université de Montréal, Montréal, Québec, Canada. 10. Department of Surgery, Université de Montréal, Montréal, Québec, Canada; Department of Hematology, Hôpital Maisonneuve-Rosemont (HMR), Montréal, Québec, Canada. 11. Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada; Division of Cardiovascular Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. Electronic address: terry.yau@uhn.ca.
Abstract
OBJECTIVES: The IMPACT-CABG trial is the first North American multicenter phase II randomized study of intramyocardial delivery of autologous CD133+ stem cells in patients with chronic ischemic cardiomyopathy undergoing coronary artery bypass grafting. The primary objective was to demonstrate safety, including freedom from major adverse cardiac events. The secondary objective was to evaluate feasibility of same-day autologous cell preparation. Although the trial was not powered to evaluate LV function, exploratory data were collected. METHODS: After 7 open-label patients who received cells, patients randomly received stem cells or placebo (N = 40 total, 20 per center). After completion of coronary anastomoses, up to 10 million CD133+, CD34+, CD45+ triple-positive cells or placebo were injected into the infarct and border zones. Patients were followed up clinically and underwent magnetic resonance imaging preoperatively and after 6 months. RESULTS: There were no procedural complications from bone marrow isolation and cell injection, no in-hospital mortality, and no protocol-related complications. Four patients had transient renal insufficiency, with 1 death during 6-month follow-up. Magnetic resonance imaging revealed that left ventricular volumes and ejection fractions improved in all patients (no difference between groups). CONCLUSIONS: The trial successfully met both primary and secondary objectives, demonstrating that same-day isolation and autologous CD133+ cell delivery with coronary artery bypass grafting is safe and feasible. The positive findings support a larger randomized, multicenter trial, with higher numbers of transplanted cells to demonstrate beneficial effects. The upcoming IMPACT-CABG II trial will evaluate higher cell doses and pharmacologic enhancement to determine whether these cells improve perfusion and myocardial function.
RCT Entities:
OBJECTIVES: The IMPACT-CABG trial is the first North American multicenter phase II randomized study of intramyocardial delivery of autologous CD133+ stem cells in patients with chronic ischemic cardiomyopathy undergoing coronary artery bypass grafting. The primary objective was to demonstrate safety, including freedom from major adverse cardiac events. The secondary objective was to evaluate feasibility of same-day autologous cell preparation. Although the trial was not powered to evaluate LV function, exploratory data were collected. METHODS: After 7 open-label patients who received cells, patients randomly received stem cells or placebo (N = 40 total, 20 per center). After completion of coronary anastomoses, up to 10 million CD133+, CD34+, CD45+ triple-positive cells or placebo were injected into the infarct and border zones. Patients were followed up clinically and underwent magnetic resonance imaging preoperatively and after 6 months. RESULTS: There were no procedural complications from bone marrow isolation and cell injection, no in-hospital mortality, and no protocol-related complications. Four patients had transient renal insufficiency, with 1 death during 6-month follow-up. Magnetic resonance imaging revealed that left ventricular volumes and ejection fractions improved in all patients (no difference between groups). CONCLUSIONS: The trial successfully met both primary and secondary objectives, demonstrating that same-day isolation and autologous CD133+ cell delivery with coronary artery bypass grafting is safe and feasible. The positive findings support a larger randomized, multicenter trial, with higher numbers of transplanted cells to demonstrate beneficial effects. The upcoming IMPACT-CABG II trial will evaluate higher cell doses and pharmacologic enhancement to determine whether these cells improve perfusion and myocardial function.
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