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. Radovanovic, Slavica Beleslin, Branko Merkely, Bela Musialek, Piotr Wojakowski, Wojciech Andreka, Peter
Bartunek, Jozef
Terzic, Andre
Davison, Beth A.
Filippatos, Gerasimos S.
Radovanovic, Slavica
Beleslin, Branko
Merkely, Bela
Musialek, Piotr
Wojakowski, Wojciech
Andreka, Peter
Publication Date
2016-12-23
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Article
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Bartunek, Jozef; Terzic, Andre; Davison, Beth A. Filippatos, Gerasimos S.; Radovanovic, Slavica; Beleslin, Branko; Merkely, Bela; Musialek, Piotr; Wojakowski, Wojciech; Andreka, Peter; Horvath, Ivan G.; Katz, Amos; Dolatabadi, Dariouch; El Nakadi, Badih; Arandjelovic, Aleksandra; Edes, Istvan; Seferovic, Petar M.; Obradovic, Slobodan; Vanderheyden, Marc; Jagic, Nikola; Petrov, Ivo; Atar, Shaul; Halabi, Majdi; Gelev, Valeri L.; Shochat, Michael K.; Kasprzak, Jaroslaw D.; Sanz-Ruiz, Ricardo; Heyndrickx, Guy R.; Nyolczas, Noémi; Legrand, Victor; Guédès, Antoine; Heyse, Alex; Moccetti, Tiziano; Fernandez-Aviles, Francisco; Jimenez-Quevedo, Pilar; Bayes-Genis, Antoni; Hernandez-Garcia, Jose Maria; Ribichini, Flavio; Gruchala, Marcin; Waldman, Scott A.; Teerlink, John R.; Gersh, Bernard J.; Povsic, Thomas J.; Henry, Timothy D.; Metra, Marco; Hajjar, Roger J.; Tendera, Michal; Behfar, Atta; Alexandre, Bertrand; Seron, Aymeric; Stough, Wendy Gattis; Sherman, Warren; Cotter, Gad; Wijns, William; , (2016). 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 38 (9), 648-660
Abstract
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 200-370mL (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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Oxford University Press (OUP)
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Attribution-NonCommercial-NoDerivs 3.0 Ireland