Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial.

Bartunek, Jozef;Terzic, Andre;Davison, Beth A;Filippatos, Gerasimos S;CHART Program;et.al.
(2017) European Heart Journal (English Edition) — Vol. 38, n° 9, p. 648-660 (2017)

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Authors
  • Bartunek, Jozef
    Author
  • Terzic, Andre
    Author
  • Davison, Beth A
    Author
  • Filippatos, Gerasimos S
    Author
  • Guedes, AntoineUCLouvain
    Author
  • CHART Program
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Abstract
(en) AIMS: Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort. METHODS AND RESULTS: This multinational, randomized, double-blind, sham-controlled study was conducted in 39 hospitals. Patients with symptomatic ischaemic heart failure on guideline-directed therapy (n = 484) were screened; n = 348 underwent bone marrow harvest and mesenchymal stem cell expansion. Those achieving > 24 million mesenchymal stem cells (n = 315) were randomized to cardiopoietic cells delivered endomyocardially with a retention-enhanced catheter (n = 157) or sham procedure (n = 158). Procedures were performed as randomized in 271 patients (n = 120 cardiopoietic cells, n = 151 sham). The primary efficacy endpoint was a Finkelstein-Schoenfeld hierarchical composite (all-cause mortality, worsening heart failure, Minnesota Living with Heart Failure Questionnaire score, 6-min walk distance, left ventricular end-systolic volume, and ejection fraction) at 39 weeks. The primary outcome was neutral (Mann-Whitney estimator 0.54, 95% confidence interval [CI] 0.47-0.61 [value > 0.5 favours cell treatment], P = 0.27). Exploratory analyses suggested a benefit of cell treatment on the primary composite in patients with baseline left ventricular end-diastolic volume 200-370 mL (60% of patients) (Mann-Whitney estimator 0.61, 95% CI 0.52-0.70, P = 0.015). No difference was observed in serious adverse events. One (0.9%) cardiopoietic cell patient and 9 (5.4%) sham patients experienced aborted or sudden cardiac death. CONCLUSION: The primary endpoint was neutral, with safety demonstrated across the cohort. Further evaluation of cardiopoietic cell therapy in patients with elevated end-diastolic volume is warranted.
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Bartunek, J., Terzic, A., Davison, B. A., Filippatos, G. S., Radovanovic, S., Beleslin, B., Merkely, B., Musialek, P., Wojakowski, W., Andreka, P., Horvath, I. G., Katz, A., Dolatabadi, D., El Nakadi, B., Arandjelovic, A., Edes, I., Seferovic, P. M., Obradovic, S., Vanderheyden, M., et al. (2017). Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial. European Heart Journal (English Edition), 38(9), 648-660. https://doi.org/10.1093/eurheartj/ehw543 (Original work published 2017)