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

Fizzah Choudry, Stephen Hamshere, Natalie Saunders, Jessry Veerapen, Katrine Bavnbek, Charles Knight, Denis Pellerin, Didier Locca, Mark Westwood, Roby Rakhit, Tom Crake, Jens Kastrup, Mahesh Parmar, Samir Agrawal, Daniel Jones, John Martin, Anthony Mathur, Fizzah Choudry, Stephen Hamshere, Natalie Saunders, Jessry Veerapen, Katrine Bavnbek, Charles Knight, Denis Pellerin, Didier Locca, Mark Westwood, Roby Rakhit, Tom Crake, Jens Kastrup, Mahesh Parmar, Samir Agrawal, Daniel Jones, John Martin, Anthony Mathur

Abstract

Aims: Clinical 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 results: A 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.

Conclusion: The 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.

Trial registration: ClinicalTrials.gov NCT00765453.

Keywords: Acute myocardial infarction; Cardiac magnetic resonance imaging; Primary percutaneous coronary intervention; Stem cell therapy.

© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

Figures

Figure 1
Figure 1
Consort diagram. Flow chart of the study design summarizing flow of participants through the trial.
Figure 2
Figure 2
Endpoint analysis of left ventricular ejection fraction. Box and whisker plots (median and range, mean shown by +) including individual data points of left ventricular ejection fraction measured at (A) baseline and 1 year (significance measured by paired t-test); (B) baseline, 3 months, and 1 year (significance measured by repeated measures analysis of variance). Participant groups (a) intracoronary placebo infusion, (b) intracoronary BMC infusion.

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