COMPARE CPM-RMI Trial: Intramyocardial Transplantation of Autologous Bone Marrow-Derived CD133+ Cells and MNCs during CABG in Patients with Recent MI: A Phase II/III, Multicenter, Placebo-Controlled, Randomized, Double-Blind Clinical Trial
نویسندگان
1 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
2 Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
3 Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
4 7Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
5 9Transplantation Research Center, NRITLD, Masih Daneshvari Hospital, Shaheed Beheshti University of Medical Science, Darabad, Niavaran, Tehran, Iran
6 0Department of Internal Medicine, Baqiyatallah Hospital, T ehran, Iran
7 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
8 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran ;Student Research Committee, School of Nursing and Midwifery , Shahid Beheshti
9 4Department of Hematology and Oncology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
10 5Department of Heart Failure and Transplantation, Fellowship in Heart Failure and Transplantation, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
11 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
12 Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
13 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
14 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
15 7Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
16 7Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
17 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
18 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
19 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
20 Department of Surgery, Baqiyatallah Hospital, Tehran, Iran
21 9Transplantation Research Center, NRITLD, Masih Daneshvari Hospital, Shaheed Beheshti University of Medical Science, Darabad, Niavaran, Tehran, Iran
22 4Department of Echocardiography, Baqiyatallah Hospital, Tehran, Iran
23 5Department of Cardiology, Baqiyatallah Hospital, Tehran, Iran
24 6Department of Cardiac Surgery, Lavasani Hospital, Social Security Organization, Tehran, Iran
25 8Department of Nuclear Medicine, Hasheminejad Hospital, Tehran University of Medical Sciences, Tehran, Iran
26 6Department of Cardiac Surgery, Lavasani Hospital, Social Security Organization, Tehran, Iran
27 Echocardiography Research Center, Rajaie Cardiovascular Medical and Research Center , Iran University of Medical Sciences, Tehran, Iran
28 Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
29 Department of Pediatrics, Ali Asghar Pediatric Hospital, Tehran University of Medical Sciences, Tehran, Iran
30 0Department of Internal Medicine, Baqiyatallah Hospital, T ehran, Iran
31 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
32 8Department of Nuclear Medicine, Hasheminejad Hospital, Tehran University of Medical Sciences, Tehran, Iran
33 Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
34 6Department of Internal Medicine, Lavasani Hospital, Social Security Organization, Tehran, Iran
35 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
36 8Department of Reproductive Imaging, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
37 9Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
38 0School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, South Australia, Australia
doi
10.22074/cellj.2018.6018چکیده
ObjectiveThe regenerative potential of bone marrow-derived mononuclear cells (MNCs) and CD133+ stem cells in the heart varies in terms of their pro-angiogenic effects. This phase II/III, multicenter and double-blind trial is designed to compare the functional effects of intramyocardial autologous transplantation of both cell types and placebo in patients with recent myocardial infarction (RMI) post-coronary artery bypass graft. Materials and Methods: This was a phase II/III, randomized, double-blind, placebo-controlled trial COMPARE CPM-RMI (CD133, Placebo, MNCs - recent myocardial infarction) conducted in accordance with the Declaration of Helsinki that assessed the safety and efficacy of CD133 and MNCs compared to placebo in patients with RMI. We randomly assigned 77 eligible RMI patients selected from 5 hospitals to receive CD133+ cells, MNC, or a placebo. Patients underwent gated single photon emission computed tomography assessments at 6 and 18 months post-intramyocardial transplantation. We tested the normally distributed efficacy outcomes with a mixed analysis of variance model that used the entire data set of baseline and between-group comparisons as well as within subject (time) and group×time interaction terms. Results: There were no related serious adverse events reported. The intramyocardial transplantation of both cell types increased left ventricular ejection fraction by 9% [95% confidence intervals (CI): 2.14% to 15.78%, P=0.01] and improved decreased systolic wall thickening by -3.7 (95% CI: -7.07 to -0.42, P=0.03). The CD133 group showed significantly decreased non-viable segments by 75% (P=0.001) compared to the placebo and 60% (P=0.01) compared to the MNC group. We observed this improvement at both the 6- and 18-month time points. Conclusion: Intramyocardial injections of CD133+ cells or MNCs appeared to be safe and efficient with superiority of CD133+ cells for patients with RMI. Although the sample size precluded a definitive statement about clinical outcomes, these results have provided the basis for larger studies to confirm definitive evidence about the efficacy of these cell types (Registration Number: NCT01167751).
