A randomized double-blind control study of early intra-coronary autologous bone marrow cell infusion in acute myocardial infarction: the REGENERATE-AMI clinical trial

Abstract

AimsClinical trials suggest that intracoronary delivery of autologous bone marrow-derived cells (BMCs) 1–7 days post-acute myocardial infarction (AMI) may improve left ventricular (LV) function. Earlier time points have not been evaluated. We sought to determine the effect of intracoronary autologous BMC on LV function when delivered within 24 h of successful reperfusion therapy.Methods and resultsA multi-centre phase II randomized, double-blind, and placebo-controlled trial. One hundred patients with anterior AMI and significant regional wall motion abnormality were randomized to receive either intracoronary infusion of BMC or placebo (1:1) within 24 h of successful primary percutaneous intervention (PPCI). The primary endpoint was the change in left ventricular ejection fraction (LVEF) between baseline and 1 year as determined by advanced cardiac imaging. At 1 year, although LVEF increased compared with baseline in both groups, the between-group difference favouring BMC was small (2.2%; 95% confidence interval, CI: −0.5 to 5.0; P = 0.10). However, there was a significantly greater myocardial salvage index in the BMC-treated group compared with placebo (0.1%; 95% CI: 0.0–0.20; P = 0.048). Major adverse events were rare in both treatment groups.ConclusionThe early infusion of intracoronary BMC following PPCI for patients with AMI and regional wall motion abnormality leads to a small non-significant improvement in LVEF when compared with placebo; however, it may play an important role in infarct remodelling and myocardial salvage.Clinical trial registrationClinicaltrials.gov NCT00765453 and EudraCT 2007-002144-16.

Stem‐cell therapy in ST‐segment elevation myocardial infarction with reduced ejection fraction: A multicenter, double‐blind randomized trial

“…20,21 About a decade ago, 2 randomized clinical trials showed, in the short run (≤6 months), better LV remodeling in patients given intracoronary bone marrow-derived cells. [22][23][24] By contrast, other trials failed to show LV function improvement, although they demonstrated reduction in infarct size, [25][26][27][28] whereas others failed to report any benefit. [29][30][31][32] Two recently published meta-analyses 33,34 showed similar results: cell treatment led to significant improvement in LVEF (by 2%-5%) when measured by echocardiography, single-photon emission computed tomography, and left ventriculography, but not with magnetic resonance imaging (MRI).…”

Concise Review: Mending a Broken Heart: The Evolution of Biological Therapeutics

“…Early clinical trials such as TOPCARE-CHD [15], REPAIR-AMI [9], and FINCELL [10] reported improved systolic function in treated acute MI (AMI) patients, while others reported either no significant improvements (ASTAMI, Leuven-AMI) [7,8] or absence of any long-term benefits (BOOST) [6]. More recent trials with larger cohorts that were adequately controlled (FOCUS-CCTRN, TIME, Late TIME, REGENERATE-AMI) [11][12][13][14] found modest or no effect of BMC therapy on ventricular function and prespecified endpoints. Overall, all trials failed to show any improvements in clinical outcomes in the treated patients.…”

New Strategies for Myocardial Infarction Treatment

“…Animal experiments showed that stem cell transplantation can contribute to the regeneration of cardiomyocyte and improve cardiac function [11,12] . Some of the stem cell types are being applied in clinical trials to prove it an acceptable and applicable treatment in human [13,14] . There are two main types of stem cells used in myocardium regeneration, pluripotent stem cells including embryonic stem cells (ESC) and induced pluripotent stem (iPS), and adult stem cells including mesenchymal stem cells, skeletal muscle myoblast cardiac stem cells (CSC) and bone marrow cells (BMC) (Figure 1).…”

“…Clinical follow-up of BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) trial indicated that intracoronary autologous BMC transfer leads to a mid-term improvement in echocardiographic parameters of diastolic function in patients after AMI [33,34] . Currently, the study of the effect of intracoronary autologous BMC on left ventricular (LV) function within 24 h after successful reperfusion therapy demonstrates that intracoronary delivery of autologous BMC leads to an insignificant improvement in LV function at an early time point (< 24 h), but it demonstrates the safety and feasibility of clinically early intracoronary injection of BMC and suggests a vital role of BMC therapy in myocardial salvage and ventricular remodeling [14] . BMC therapy treated AMI patients displayed a better quality of life (QoL) at 3 and 12 months post-AMI than the control-group patients [35] .…”