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; Hossein Ahmadi, Zargham; Madani, Hoda; Sadeghian, Hakimeh; Ahmadi Tafti, Seyed Hossein; Moshkani Farahani, Maryam; Kazemi Saleh, Davood; Hosseinnejad, Hossein; Hosseini, Saeid; Hekmat, Sepideh; Zargham, Hossein Ahmadi; Dehghani, Majid; Saadat, Alireza; Mardpour, Soura; Hosseini, Seyedeh Esmat; Esmaeilzadeh, Maryam; Sadeghian, Hakimeh , 3,  , 13,  , M.D.14,  ,
              M.D.15,; Bahoush, Gholamreza; Bassi, Ali; Amin, Ahmad; Fazeli, Roghayeh; Sharafi, Yaser; Arab, Leila; Movahhed, Mansour; Davaran, Saeid; Ramezanzadeh, Narges; Kouhkan, Azam; Hezavehei, Ali; Namiri, Mehrnaz; Kashfi, Fahimeh; Akhlaghi, Ali; Sotoodehnejadnematalahi, Fattah; Vosough Dizaji, Ahmad; Gourabi, Hamid; Syedi, Naeema; Shahverdi, Abdolhosein; Baharvand, Hossein; Aghdami, Nasser

doi:10.22074/cellj.2018.5197

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 : Correction

Authors

Mohammad Hassan Naseri ¹
Zargham Hossein Ahmadi ²
Hoda Madani ³
Hakimeh Sadeghian ⁴
Seyed Hossein Ahmadi Tafti ⁴
Maryam Moshkani Farahani ⁵
Davood Kazemi Saleh ⁶
Hossein Hosseinnejad ⁷
Saeid Hosseini ⁸
Sepideh Hekmat ⁹
Hossein Ahmadi Zargham ²
Majid Dehghani ⁷
Alireza Saadat ¹⁰
Soura Mardpour ³
Seyedeh Esmat Hosseini ¹¹
Maryam Esmaeilzadeh ¹²
Hakimeh , 3, , 13, , M.D.14, , M.D.15, Sadeghian ⁴
Gholamreza Bahoush ¹³
Ali Bassi ¹⁴
Ahmad Amin ¹⁵
Roghayeh Fazeli ³
Yaser Sharafi ¹⁰
Leila Arab ³
Mansour Movahhed ⁹
Saeid Davaran ⁴
Narges Ramezanzadeh ⁴
Azam Kouhkan ³
Ali Hezavehei ¹⁶
Mehrnaz Namiri ³
Fahimeh Kashfi ¹⁷
Ali Akhlaghi ¹⁷
Fattah Sotoodehnejadnematalahi ³
Ahmad Vosough Dizaji ¹⁸
Hamid Gourabi ¹⁹
Naeema Syedi ²⁰
Abdolhosein Shahverdi ³
Hossein Baharvand ³
Nasser Aghdami ³

¹ Department of Surgery, Baqiyatallah Hospital, Tehran, Iran

² 9Transplantation Research Center, NRITLD, Masih Daneshvari Hospital, Shaheed Beheshti University of Medical Science, Darabad, Niavaran, Tehran, Iran

³ Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

⁴ Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran

⁵ 4Department of Echocardiography, Baqiyatallah Hospital, Tehran, Iran

⁶ 5Department of Cardiology, Baqiyatallah Hospital, Tehran, Iran

⁷ 6Department of Cardiac Surgery, Lavasani Hospital, Social Security Organization, Tehran, Iran

⁸ 7Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

⁹ 8Department of Nuclear Medicine, Hasheminejad Hospital, Tehran University of Medical Sciences, Tehran, Iran

¹⁰ 0Department of Internal Medicine, Baqiyatallah Hospital, T ehran, Iran

¹¹ 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

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 4Department of Hematology and Oncology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran

¹⁵ 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

¹⁶ 6Department of Internal Medicine, Lavasani Hospital, Social Security Organization, Tehran, Iran

¹⁷ 7Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

¹⁸ 8Department of Reproductive Imaging, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

¹⁹ 9Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

²⁰ 0School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, South Australia, Australia

10.22074/cellj.2018.5197

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).