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)
Bibliographical noteFunding Information:
The full rationale and design of the RENEW trial has been published elsewhere (22) . RENEW was a randomized, double-blind, multicenter trial conducted at 45 centers in the United States ( NCT01508910 ). An academic steering committee with sponsor representation helped to design the trial and was responsible for its conduct and for presentation and publication of the results. The trial was monitored by a data and safety monitoring board of independent physicians and a statistician with expertise in cardiovascular diseases and hematology; the data and safety monitoring board had access to unblinded data. The protocol was approved by appropriate regulatory and ethical boards at each site and conducted in compliance with the provisions of the Declaration of Helsinki. The trial was sponsored by Baxter Healthcare (Deerfield, Illinois).
© 2016 American College of Cardiology Foundation
- interventional therapy
- progenitor cell
- stable coronary disease
- stem cell