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

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 200-370 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.

• Authors: Jozef Bartunek, Andre Terzic, Beth A Davison, Gerasimos S Filippatos, Slavica Radovanovic, Branko Beleslin, Bela Merkely, Piotr Musialek, Wojciech Wojakowski, Peter Andreka, Ivan G Horvath, Amos Katz, Dariouch Dolatabadi, Badih El Nakadi, Aleksandra Arandjelovic, Istvan Edes, Petar M Seferovic, Slobodan Obradovic, Marc Vanderheyden, Nikola Jagic, Ivo Petrov, Shaul Atar, Majdi Halabi, Valeri L Gelev, Michael K Shochat, Jaroslaw D Kasprzak, Ricardo Sanz-Ruiz, Guy R Heyndrickx, Noémi Nyolczas, Victor Legrand, Antoine Guédès, Alex Heyse, Tiziano Moccetti, Francisco Fernandez-Aviles, Pilar Jimenez-Quevedo, Antoni Bayes-Genis, Jose Maria Hernandez-Garcia, Flavio Ribichini, Marcin Gruchala, Scott A Waldman, John R Teerlink, Bernard J Gersh, Thomas J Povsic, Timothy D Henry, Marco Metra, Roger J Hajjar, Michal Tendera, Atta Behfar, Bertrand Alexandre, Aymeric Seron, Wendy Gattis Stough, Warren Sherman, Gad Cotter, William Wijns, CHART Program
• Journal: European heart journal (Eur Heart J) Vol. 38 Issue 9 Pg. 648-660 (Mar 01 2017) ISSN: 1522-9645 [Electronic] England
• PMID: 28025189 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Topics

• Adult
• Aged
• Double-Blind Method
• Female
• Heart Failure (therapy)
• Humans
• Male
• Mesenchymal Stem Cell Transplantation (methods)
• Middle Aged
• Myocardial Ischemia (therapy)
• Prospective Studies
• Treatment Outcome
• Young Adult