Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial.
- Bartunek J Cardiovascular Center, Onze-Lieve-Vrouwziekenhuis OLV Hospital, Moorselbaan 164, Aalst, B-9300, Aalst, Belgium.
- Terzic A Mayo Clinic, Center for Regenerative Medicine, Department of Cardiovascular Diseases, 200 First Street SW, Rochester, Minnesota 550905, USA.
- Davison BA Momentum Research, Inc, Durham, NC, USA.
- Filippatos GS National and Kapodistrian University of Athens, School of Medicine, Attikon University Hospital, Athens, Greece.
- Radovanovic S University Hospital Center Bezanijska Kosa, Belgrade, Serbia.
- Beleslin B Cardiology Clinic, Clinical Centre of Serbia, Medical School, University of Belgrade, Belgrade, Serbia.
- Merkely B Semmelweis University Heart and Vascular Center, Budapest, Hungary.
- Musialek P Jagiellonian University Department of Cardiac and Vascular Diseases, John Paul II Hospital, Krakow, Poland.
- Wojakowski W Third Division of Cardiology, Medical University of Silesia, Katowice, Poland.
- Andreka P Gottsegen Gyorgy Hungarian Institute of Cardiology, Budapest, Hungary.
- Horvath IG Heart Institute, University of Pécs, Pécs, Hungary.
- Katz A Department of Cardiology, Barzilai Medical Center, Israel Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
- Dolatabadi D Division of Cardiology, Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium.
- El Nakadi B Division of Cardiology, Centre Hospitalier Universitaire de Charleroi, Charleroi, Belgium.
- Arandjelovic A Cardiology Department, Clinical Hospital Zvezdara, Belgrade, Serbia.
- Edes I Department of Cardiology, University of Debrecen, Debrecen, Hungary.
- Seferovic PM University of Belgrade School of Medicine, Belgrade University Medical Center, Belgrade, Serbia.
- Obradovic S Clinic of Emergency Medicine, Military Medical Academy, School of Medicine, University of Defense, Belgrade, Serbia.
- Vanderheyden M Cardiovascular Center, Onze-Lieve-Vrouwziekenhuis OLV Hospital, Moorselbaan 164, Aalst, B-9300, Aalst, Belgium.
- Jagic N Clinical Center Kragujevac, Kragujevac, Serbia.
- Petrov I Department of Cardiology, Angiology, and Electrophysiology, City Clinic Heart and Vascular Institute, Sofia University, Sofia, Bulgaria.
- Atar S Department of Cardiology, Galilee Medical Center, Nahariya, Israel.
- Halabi M Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, Israel.
- Gelev VL Department of Cardiology, Angiology, and Electrophysiology, City Clinic Heart and Vascular Institute, Sofia University, Sofia, Bulgaria.
- Shochat MK Heart Institute, Hillel Yaffe Medical Center, Hadera, Rappaport School of Medicine, Haifa, Israel, Technion.
- Kasprzak JD Department of Cardiology Medical University of Lodz, Lodz, Poland.
- Sanz-Ruiz R Hospital General Universitario Gregorio Marañón, Madrid, Spain.
- Heyndrickx GR Cardiovascular Center, Onze-Lieve-Vrouwziekenhuis OLV Hospital, Moorselbaan 164, Aalst, B-9300, Aalst, Belgium.
- Nyolczas N Medical Centre, Hungarian Defense Forces, Budapest, Hungary.
- Legrand V Department of Cardiology, Centre Hospitalier Universitaire de Liège, Liège, Belgium.
- Guédès A Department of Cardiology, Universite Catholique de Louvain, CHU UcL Namur, Yvoir, Belgium.
- Heyse A Department of Cardiology, AZ Glorieux, Ronse, Belgium.
- Moccetti T Cardiocentro Ticino, Lugano, Switzerland.
- Fernandez-Aviles F Hospital General Universitario Gregorio Marañón, Madrid, Spain.
- Jimenez-Quevedo P Department of Cardiology, Hospital Clínico San Carlos, Madrid, Spain.
- Bayes-Genis A Hospital Universitari Germans Trias I Pujol, Universitat Autònoma, Barcelona, Spain.
- Hernandez-Garcia JM Hospital Clinico Universitario Virgen de la Victoria, Malaga, Spain.
- Ribichini F Department of Cardiology, University of Verona, Italy.
- Gruchala M Department of Cardiology, Medical University of Gdansk, Gdansk, Poland.
- Waldman SA Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
- Teerlink JR School of Medicine, University of California San Francisco and Section of Cardiology, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.
- Gersh BJ Mayo Clinic, Center for Regenerative Medicine, Department of Cardiovascular Diseases, 200 First Street SW, Rochester, Minnesota 550905, USA.
- Povsic TJ Duke Clinical Research Institute and Duke Medicine, Durham, NC, USA.
- Henry TD Cedars Sinai Heart Institute, Los Angeles, CA, USA.
- Metra M Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University and Spedali Civili, Brescia, Italy.
- Hajjar RJ Mount Sinai School of Medicine, New York, NY, USA.
- Tendera M Third Division of Cardiology, Medical University of Silesia, Katowice, Poland.
- Behfar A Mayo Clinic, Center for Regenerative Medicine, Department of Cardiovascular Diseases, 200 First Street SW, Rochester, Minnesota 550905, USA.
- Alexandre B Celyad, Mont Saint Guibert, Belgium.
- Seron A Celyad, Mont Saint Guibert, Belgium.
- Stough WG Departments of Clinical Research and Pharmacy Practice, Campbell University College of Pharmacy and Health Sciences, Cary, NC, USA.
- Sherman W Celyad, Mont Saint Guibert, Belgium.
- Cotter G Momentum Research, Inc, Durham, NC, USA.
- Wijns W Cardiovascular Center, Onze-Lieve-Vrouwziekenhuis OLV Hospital, Moorselbaan 164, Aalst, B-9300, Aalst, Belgium.
- 2016-12-28
Published in:
- European heart journal. - 2017
Cardiopoiesis
Cardiovascular disease
Disease severity
Marker
Precision medicine
Regenerative medicine
Stem cell
Target population
Adult
Aged
Double-Blind Method
Female
Heart Failure
Humans
Male
Mesenchymal Stem Cell Transplantation
Middle Aged
Myocardial Ischemia
Prospective Studies
Treatment Outcome
Young Adult
English
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.
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.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1093/eurheartj/ehw543
- PMID 28025189
- Persistent URL
- https://folia.unifr.ch/global/documents/112709
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