Thomas J Povsic1, Timothy D Henry2, Jay H Traverse3, F David Fortuin4, Gary L Schaer5, Dean J Kereiakes6, Richard A Schatz7, Andreas M Zeiher8, Christopher J White9, Duncan J Stewart10, E Marc Jolicoeur11, Theodore Bass12, David A Henderson13, Patricia Dignacco14, Ziangoiong Gu14, Hussein R Al-Khalidi14, Candice Junge15, Adel Nada16, Andrea S Hunt17, Douglas W Losordo18. 1. Duke Clinical Research Institute, Duke Medicine, Durham, North Carolina. Electronic address: povsi001@mc.duke.edu. 2. Cedars-Sinai Heart Institute, Los Angeles, California. 3. Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, Minnesota. 4. Mayo Clinic Hospital, Phoenix, Arizona. 5. Rush University Medical Center, Chicago, Illinois. 6. The Christ Hospital Heart and Vascular Center, Cincinnati, Ohio. 7. Scripps Clinic Torrey Pines, La Jolla, California. 8. Department of Medicine, University of Frankfurt, Frankfurt, Germany. 9. Ochsner Medical Center, New Orleans, Louisiana. 10. Ottawa Hospital Research Institute, University of Ottawa, Quebec, Ontario, Canada. 11. Montreal Heart Institute, Université de Montréal, Montréal, Quebec, Canada. 12. University of Florida, Jacksonville Cardiovascular Center Jacksonville, Florida. 13. Cardiology Research Associates, Daytona Beach, Florida. 14. Duke Clinical Research Institute, Duke Medicine, Durham, North Carolina. 15. Amgen Inc. Thousand Oaks, California. 16. Intellia Therapeutics, Inc., Cambridge, Massachusetts. 17. Baxalta US Inc., Bannockburn, Illinois. 18. Caladrius Biosciences, New York, New York.
Abstract
OBJECTIVES: This study tested whether intramyocardial (IM) administration of mobilized, purified autologous CD34(+) cells would improve total exercise time (TET) and angina frequency in patients with refractory angina. BACKGROUND: IM administration of autologous CD34(+) cells has been associated consistently with improvements in functional capacity and angina symptoms in early phase clinical trials. METHODS: RENEW (Efficacy and Safety of Targeted Intramyocardial Delivery of Auto CD34+ Stem Cells for Improving Exercise Capacity in Subjects With Refractory Angina) was a randomized, double-blind, multicenter trial comparing IM CD34(+) administration with no intervention (open-label standard of care) or IM placebo injections (active control). The primary efficacy endpoint was change in TET at 12 months. Key secondary endpoints include changes in angina frequency at 3, 6, and 12 months, and TET at 3 and 6 months. The key safety analysis was the incidence of major adverse cardiovascular events through 24 months. RESULTS: The sponsor terminated the study for strategic considerations after enrollment of 112 of planned 444 patients. The difference in TET between patients treated with cell therapy versus placebo was 61.0 s at 3 months (95% confidence interval (CI): -2.9 to 124.8; p = 0.06), 46.2 s at 6 months (95% CI: -28.0 to 120.4; p = 0.22), and 36.6 s at 12 months (95% CI: -56.1 to 129.2; p = 0.43); angina frequency was improved at 6 months (relative risk: 0.63; p = 0.05). Autologous CD34(+) cell therapy seemed to be safe compared with both open-label standard of care and active control (major adverse cardiovascular events 67.9% [standard of care], 42.9% (active control), 46.0% [CD34(+)]). CONCLUSIONS: Due to early termination, RENEW was an incomplete experiment; however, the results were consistent with observations from earlier phase studies. These findings underscore the need for a definitive trial. (Efficacy and Safety of Targeted Intramyocardial Delivery of Auto CD34(+) Stem Cells for Improving Exercise Capacity in Subjects With Refractory Angina [RENEW]: NCT01508910).
RCT Entities:
OBJECTIVES: This study tested whether intramyocardial (IM) administration of mobilized, purified autologous CD34(+) cells would improve total exercise time (TET) and angina frequency in patients with refractory angina. BACKGROUND: IM administration of autologous CD34(+) cells has been associated consistently with improvements in functional capacity and angina symptoms in early phase clinical trials. METHODS: RENEW (Efficacy and Safety of Targeted Intramyocardial Delivery of Auto CD34+ Stem Cells for Improving Exercise Capacity in Subjects With Refractory Angina) was a randomized, double-blind, multicenter trial comparing IM CD34(+) administration with no intervention (open-label standard of care) or IM placebo injections (active control). The primary efficacy endpoint was change in TET at 12 months. Key secondary endpoints include changes in angina frequency at 3, 6, and 12 months, and TET at 3 and 6 months. The key safety analysis was the incidence of major adverse cardiovascular events through 24 months. RESULTS: The sponsor terminated the study for strategic considerations after enrollment of 112 of planned 444 patients. The difference in TET between patients treated with cell therapy versus placebo was 61.0 s at 3 months (95% confidence interval (CI): -2.9 to 124.8; p = 0.06), 46.2 s at 6 months (95% CI: -28.0 to 120.4; p = 0.22), and 36.6 s at 12 months (95% CI: -56.1 to 129.2; p = 0.43); angina frequency was improved at 6 months (relative risk: 0.63; p = 0.05). Autologous CD34(+) cell therapy seemed to be safe compared with both open-label standard of care and active control (major adverse cardiovascular events 67.9% [standard of care], 42.9% (active control), 46.0% [CD34(+)]). CONCLUSIONS: Due to early termination, RENEW was an incomplete experiment; however, the results were consistent with observations from earlier phase studies. These findings underscore the need for a definitive trial. (Efficacy and Safety of Targeted Intramyocardial Delivery of Auto CD34(+) Stem Cells for Improving Exercise Capacity in Subjects With Refractory Angina [RENEW]: NCT01508910).
Authors: Vincenzo Grimaldi; Alberto Zullo; Francesco Donatelli; Francesco Paolo Mancini; Francesco Cacciatore; Claudio Napoli Journal: J Thorac Dis Date: 2018-07 Impact factor: 2.895
Authors: Rahman Shah; Samuel B Latham; Sajjad A Khan; Muhammad Shahreyar; Inyong Hwang; Ion S Jovin Journal: Clin Cardiol Date: 2018-04-17 Impact factor: 2.882