Results of a phase 1, randomized, double-blind, placebo-controlled trial of bone marrow mononuclear stem cell administration in patients following ST-elevation myocardial infarction

Abstract

Background: Initial clinical trials from Europe have demonstrated that the administration of bone marrow-derived mononuclear cells (BMCs) may improve left ventricular (LV) function in patients following ST-elevation myocardial infarction (STEMI). However, results from trials performed in the United States have not yet been presented.

Methods: We developed a phase 1, randomized, placebo-controlled, double-blind trial to investigate the effects of BMC administration in patients following STEMI on recovery of LV function using cardiac magnetic resonance imaging (cMRI). Forty patients with moderate to large anterior STEMIs were randomized to 100 million intracoronary BMCs versus placebo 3 to 10 days following successful primary angioplasty and stenting (percutaneous coronary intervention) of the left anterior descending coronary artery.

Results: Administration of BMC was safely performed in a high-risk cohort with minimal major adverse clinical event rates, and all patients remain alive to date. Left ventricular ejection fraction increased from 49.0% +/- 9.5% at baseline to 55.2% +/- 9.8% at 6 months by cMRI in the BMC group (P < .05), which was not different from the increase in the placebo group (48.6% +/- 8.5% to 57.0% +/- 13.4%, P < .05). Left ventricular end-diastolic volume decreased by 4 mL/m(2) in the BMC group at 6 months but increased significantly in the placebo group (17 mL/m(2), P < .01).

Conclusions: This phase 1 study from the United States confirms the ongoing safety profile of BMC administration in patients following STEMI. The improvement in LV ejection fraction at 6 months by cMRI in the cell therapy group was not different than the placebo group. However, BMC administration had a favorable effect on LV remodeling at 6 months.

Trial registration: ClinicalTrials.gov NCT00268307.

2010 Mosby, Inc. All rights reserved.

Figures

Figure 1

Change in left-ventricular ejection fraction (LVEF) by cardiac MRI between baseline and 6 months in the 30 individual patients following bone marrow mononuclear cell (BMC) administration and in the 10 individual placebo patients (both, p

Figure 2

Change in left-ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV) by cardiac MRI between baseline, 3 and 6 months following bone marrow mononuclear cell (BMC) administration or placebo administration. BMC administration was associated with a significant improvement in LVEDV compared to the placebo group (p