Cell Therapy in Patients With Ischemic Heart Failure
What is the safety and efficacy of catheter-based transendocardial injection of ixmyelocel-T cell therapy in patients with heart failure and reduced ejection fractions?
In this randomized, double-blind, placebo-controlled phase 2B trial (ixCELL-DCM), patients from 31 sites in North America with New York Heart Association class III or IV symptomatic heart failure due to ischemic dilated cardiomyopathy, who had left ventricular ejection fraction ≤35%, an automatic implantable cardioverter-defibrillator, and who were ineligible for revascularization procedures were randomly assigned (1:1) to receive ixmyelocel-T or placebo at the time of bone marrow aspiration and followed for 12 months. Randomization was done through an interactive (voice/web) response system. The pharmacist, treating physician, and coordinator at each site were unblinded, but the follow-up team was completely blinded. The primary endpoint was a composite of all-cause death, cardiovascular admission to hospital, and unplanned clinic visits to treat acute decompensated heart failure based on the blinded adjudication of an independent clinical endpoint committee. Primary efficacy endpoint analyses and safety analyses were done by modified intention to treat.
Between April 2, 2013, and January 28, 2015, 126 participants were randomly assigned to receive either ixmyelocel-T (n = 60) or placebo (n = 66). One hundred and fourteen (90%) patients comprised the modiﬁed intention-to-treat population, and 109 (87%) patients were included in the per-protocol primary efficacy analysis (58 in the ixmyelocel-T group and 51 in the placebo group). The primary efficacy endpoint was observed in 47 patients: 50 events in 25 (49%) of 51 patients in the placebo group, and 38 events in 22 (38%) of 58 patients in the ixmyelocel-T group, which represents a 37% reduction in cardiac events compared with placebo (risk ratio, 0.63; 95% confidence interval [CI], 0.42–0.97; p = 0.0344); 41 (75%) of 51 participants in the placebo group had serious adverse events versus 31 (53%) of 58 in the ixmyelocel-T group (p = 0.0197).
The authors concluded that transendocardial delivery of ixmyelocel-T in patients with heart failure and reduced ejection fraction due to ischemic dilated cardiomyopathy resulted in a significant reduction in adjudicated clinical cardiac events compared with placebo, leading to improved patient outcomes.
This study reports that the transendocardial delivery of ixmyelocel-T resulted in a significant reduction in clinical cardiac events driven by both cardiac mortality and cardiac admissions to the hospital at 12 months compared with placebo. The improvements in clinical events seem to be more significant than the improvements in left ventricular function, and therefore, additional studies are necessary to understand the mechanism of benefit for this therapy. Finally, this study was modest in size and these results should be confirmed in larger prospective studies. The study findings are very promising and appear to suggest that cell therapy may have significant potential for the future management of heart failure.
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