Past Issue

Volume 20, Number 2, Summer 2018, Serial Number: 78, Pages: 267-277

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


Mohammad Hassan Naseri, M.D, 1, #, Hoda Madani, M.D, 2, #, Seyed Hossein Ahmadi Tafti, M.D, 3, Maryam Moshkani Farahani, M.D, 4, Davood Kazemi Saleh, M.D, 5, Hossein Hosseinnejad, M.D, 6, Saeid Hosseini, M.D, 7, Sepideh Hekmat, M.D., 8, Zargham Hossein Ahmadi, M.D, 9, Majid Dehghani, M.D, 6, Alireza Saadat, M.D, 10, Soura Mardpour, M.Sc, 2, Seyedeh Esmat Hosseini, M.Sc, 2, 11, Maryam Esmaeilzadeh, M.D., FACC., FASE., 12, Hakimeh Sadeghian, M.D, 3, Gholamreza Bahoush, M.D., 13, Ali Bassi, M.D, 14, Ahmad Amin, M.D, , Roghayeh Fazeli, M.D, 2, Yaser Sharafi, M.D., 10, Leila Arab, M.D, 2, Mansour Movahhed, M.D., 8, Saeid Davaran, M.D, 3, Narges Ramezanzadeh, B.Sc, 3, Azam Kouhkan, M.D., 2, Ali Hezavehei, M.D., 16, Mehrnaz Namiri, M.Sc, 2, Fahimeh Kashfi, M.Sc., 17, Ali Akhlaghi, M.Sc., 17, Fattah Sotoodehnejadnematalahi, Ph.D., 2, Ahmad Vosough Dizaji, M.Sc., 18, Hamid Gourabi, Ph.D., 19, Naeema Syedi, Ph.D, 20, Abdolhosein Shahverdi, Ph.D, 2, Hossein Baharvand, Ph.D, 2, Nasser Aghdami, Ph.D, 2, *,
Department of Surgery, Baqiyatallah University of Medical Sceinces, Tehran, Iran
Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Research Department, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
Department of Echocardiography, Baqiyatallah University of Medical Sceinces, Tehran, Iran
Department of Cardiology, Baqiyatallah University of Medical Sceinces, Tehran, Iran
Department of Cardiac Surgery, Lavasani Hospital, Social Security Organization, Tehran, Iran
Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
Department of Nuclear Medicine, Hasheminejad Hospital, Tehran University of Medical Sciences, Tehran, Iran
Transplantation Research Center, NRITLD, Masih Daneshvari Hospital, Shaheed Beheshti University of Medical Science, Darabad, Niavaran, Tehran, Iran
Department of Internal Medicine, Baqiyatallah University of Medical Sceinces, T ehran, Iran
Student Research Committee, School of Nursing and Midwifery , Shahid Beheshti University of Medical Sciences, Tehran, Iran
Echocardiography Research Center, Rajaie Cardiovascular Medical and Research Center , Iran University of Medical Sciences, Tehran, Iran
Department of Pediatrics, Ali Asghar Pediatric Hospital, Tehran University of Medical Sciences, Tehran, Iran
Department of Hematology and Oncology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
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
Department of Internal Medicine, Lavasani Hospital, Social Security Organization, Tehran, Iran
Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Department of Reproductive Imaging, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran
School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, South Australia, Australia
*Corresponding Address: P.O.Box: 16635-148 Department of Regenerative Medicine Cell Science Research Center Royan Institute for Stem Cell Biology and Technology ACECR Tehran Iran Email:Nasser.aghdami@royaninstitute.org

The first two authors equally contributed to this article.

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).