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

Naseri, Mohammad Hassan; Madani, Hoda; Ahmadi Tafti, Seyed Hossein; Farahani, Maryam Moshkani; Kazemi Saleh, Davood; Hosseinnejad, Hossein; Hosseini, Saeid; Hekmat, Sepideh; Ahmadi, Zargham Hossein; Dehghani, Majid; Saadat, Alireza; Mardpour, Soura; Hosseini, Seyedeh Esmat; Esmaeilzadeh, Maryam; Sadeghian, Hakimeh; Bahoush, Gholamreza; Bassi, Ali; Amin, Ahmad; Fazeli, Roghayeh; Sharaf, Yaser; Arab, Leila; Movahhed, Mansour; Davaran, Saeid; Ramezanzadeh, Narges; Kouhkan, Azam; Hezavehei, Ali; Namiri, Mehrnaz; Kashfi, Fahimeh; Akhlaghi, Ali; Sotoodehnejadnematalahi, Attah; Vosough Dizaji, Ahmad; Gourabi, Hamid; Syedi, Naeema; Shahverdi, Abdolhosein; Baharvand, Hossein; Aghdami, Nasser

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

Document Type : Original Article

Authors

¹ Department of Surgery, Baqiyatallah University of Medical Sceinces, Tehran, Iran

² Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

³ Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran

⁴ Department of Echocardiography, Baqiyatallah University of Medical Sceinces, Tehran, Iran

⁵ Department of Cardiology, Baqiyatallah University of Medical Sceinces, Tehran, Iran

⁶ Department of Cardiac Surgery, Lavasani Hospital, Social Security Organization, Tehran, Iran

⁷ Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

⁸ Department of Nuclear Medicine, Hasheminejad Hospital, Tehran University of Medical Sciences, Tehran, Iran

⁹ Transplantation Research Center, NRITLD, Masih Daneshvari Hospital, Shaheed Beheshti University of Medical Science, Darabad, Niavaran, Tehran, Iran

¹⁰ Department of Internal Medicine, Baqiyatallah University of Medical Sceinces, Tehran, Iran

¹¹ Student Research Committee, School of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran

¹² Echocardiography Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

¹³ Department of Pediatrics, Ali Asghar Pediatric Hospital, Tehran University of Medical Sciences, Tehran, Iran

¹⁴ Department of Hematology and Oncology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran

¹⁵ Department of Heart Failure and Transplantation, Fellowship in Heart Failure and Transplantation, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

¹⁶ Department of Internal Medicine, Lavasani Hospital, Social Security Organization, Tehran, Iran

¹⁷ Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

¹⁸ Sotoodehnejadnematalahi

¹⁹ Vosough Dizaji

²⁰ Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

²¹ School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, South Australia, Australia

²² Department of Regenerative Biomedicine and Cell Terapy, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

Abstract

Objective: The 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).

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